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  • 201.
    Olkku, Anu
    et al.
    School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Leskinen, Jarkko
    Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Hynynen, Kullervo
    Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland; Department of Medical Biophysics, University of Toronto and Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Canada.
    Mahonen, Anitta
    chool of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Finland; Bone and Cartilage Research Unit, University of Eastern Finland, Kuopio, Finland.
    Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells.2010In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 47, no 2, p. 320-330, article id 20435172Article in journal (Refereed)
    Abstract [en]

    The benefit from an ultrasound (US) exposure for fracture healing has been clearly shown. However, the molecular mechanisms behind this effect are not fully known. Recently, the canonical Wnt signaling pathway has been recognized as one of the essential regulators of osteoblastogenesis and bone mass, and thereby considered crucial for bone health. Mechanical loading and fluid shear stress have been reported to activate the canonical Wnt signaling pathway in bone cells, but previous reports on the effects of therapeutic US on Wnt signaling in general or in bone, in particular, have not been published yet. Therefore, activation of Wnt signaling pathway was assayed in human osteoblastic cells, and indeed, this pathway was found to be activated in MG-63 cells through the phosphoinositol 3-kinase/Akt (PI3K/Akt) and mTOR cascades following a single 10 min US exposure (2 W, 1.035 MHz). In addition to the reporter assay results, the Wnt pathway activation was also observed as nuclear localization of beta-catenin. Wnt activation showed also temperature dependence at elevated temperatures, and the expression of canonical Wnt ligands was induced under the thermal exposures. However, existence of a specific, non-thermal US component was evident as well, perhaps evidence of a potential dual action of therapeutic US on bone. Neither US nor heat exposures affected cell viability in our experiments. In summary, this is the first study to report that Wnt signaling cascade, important for osteoblast function and bone health, is one of the pathways activated by therapeutic US as well as by hyperthermia in human osteoblastic cells. Our results provide evidence for the potential molecular mechanisms behind the beneficial effects of US on fracture healing. Combinations of US, heat, and possible pharmacological treatment could provide useful flexibility for clinical cases in treating various bone disorders.

  • 202.
    Otten, Volker
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Maguire, Gerald Q. Jr.
    Noz, Marilyn E.
    Zeleznik, Michael P.
    Nilsson, Kjell G.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Olivecrona, Henrik
    Are CT Scans a Satisfactory Substitute for the Follow-Up of RSA Migration Studies of Uncemented Cups?: A Comparison of RSA Double Examinations and CT Datasets of 46 Total Hip Arthroplasties2017In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, Vol. 2017, article id 3681458Article in journal (Refereed)
    Abstract [en]

    As part of the 14-year follow-up of a prospectively randomized radiostereometry (RSA) study on uncemented cup fixation, two pairs of stereo radiographs and a CT scan of 46 hips were compared. Tantalum beads, inserted during the primary operation, were detected in the CT volume and the stereo radiographs and used to produce datasets of 3D coordinates. The limit of agreement between the combined CT and RSA datasets was calculated in the same way as the precision of the double RSA examination. The precision of RSA corresponding to the 99% confidence interval was 1.36 degrees, 1.36 degrees, and 0.60 degrees for X-, Y-, and Z-rotation and 0.40, 0.17, and 0.37mm for X-, Y-, and Z-translation. The limit of agreement between CT and RSA was 1.51 degrees, 2.17 degrees, and 1.05 degrees for rotation and 0.59, 0.56, and 0.74mm for translation. The differences between CT and RSA are close to the described normal 99% confidence interval for precision in RSA: 0.3 degrees to 2 degrees for rotation and 0.15 to 0.6mm for translation. We conclude that measurements using CT and RSA are comparable and that CT can be used for migration studies for longitudinal evaluations of patients with RSA markers.

  • 203.
    Otten, Volker
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Maguire Jr, Gerald Q.
    Noz, Marilyn E.
    Zeleznik, Michael P.
    Nilsson, Kjell G.
    Olivecrona, Henrik
    Are migration measurements from CT and RSA comparable?: A study using 45 patients with hip prostheses at 14 yearsManuscript (preprint) (Other academic)
  • 204.
    Otten, Volker T C
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    The Uncemented Cup in Total Hip Arthroplasty: stability, Wear and Osteolysis2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Artificial hip joint replacement has undergone tremendous development in the past 100 years. In the beginning, complications, such as infection and early loosening, were the rule rather than the exception. Today, complications of any sort are rare during the first decade after the operation. Artificial hip joint replacement has been chosen as the "Operation of the Century" and has dramatically improved the quality of life of millions of patients. Unfortunately, in the long-term, prosthesis loosening due to pathological bone resorption (osteolysis) around the prosthesis is still common. Traditionally, the prosthesis is anchored in the bone with bone cement (Plexiglas). However, since this cementation method was suspected to cause late loosening, alternative methods, such as the implantation of so-called uncemented prostheses, have been developed and are being increasingly applied. Because the early movement of a prosthesis (migration) increases the risk of loosening, uncemented cups are often augmented with additional screws. The mechanisms regulating the early and late loosening of uncemented cups are not fully established. Wear particles from the artificial joint and intermittent fluid pressure on the bone appear to accelerate or even cause bone loss and can eventually lead to loosening of the prosthesis. Therefore, screw holes in the uncemented cup have been suspected to be a risk factor.

    Aims: We have studied whether the additional augmentation of modern uncemented cups with screws, pegs or hydroxyapatite increases the long-term stability, affects the wear rate, influences the development of osteolysis, or has any impact on the risk of cup revision. Furthermore, we investigated whether computed tomography (CT), which is needed to detect osteolysis around the prosthesis, could also be used in the follow-up of migration studies without losing significant precision compared to radiostereometry (RSA), which is the gold standard for these measurements.

    Patients and Methods: In studies I-III, we evaluated 48 hips (45 patients) randomized to receive cups with or without augmentation. As part of the 14-year follow-up with conventional radiographs of the pelvis, two pairs of stereo radiographs and a CT scan were obtained. Migration and wear were measured by RSA. The volume and type of osteolysis were determined on CT. Furthermore, we calculated the precision and limit of agreement of RSA and CT to compare these two modalities as tools for migration measurements.

    In study IV, we compared the risk of cup revision between 10,371 uncemented cups with and 12,354 without screw holes, using data from the Swedish Hip Arthroplasty Register.

    Results: Study I: Cup stability was equally good regardless of cup augmentation. The mean wear rate of the cup liner was high, at 0.21 mm/year, with no significant difference between the groups.

    Study II: The limit of agreement between CT and RSA was 1.15°, 1.51°, and 0.70° for rotation and 0.46, 0.43, and 0.52 mm for translation. These results were within the described normal 99% confidence limits for precision in RSA: 0.3° to 2° for rotation and 0.15 to 0.6 mm for translation.

    Study III: Osteolysis of some degree was visible in all 48 hips on CT. We found three different types of osteolytic lesions: type 1A, absent trabecular bone and a sclerotic border around the lesion; type 1B, absent trabecular bone and no sclerotic border; and type 2, reduced radiodensity and reduced trabecular number. Cups with screw holes were surrounded with larger osteolytic lesions, and osteolysis around these cups was more likely to be a type 1A lesion.

    Study IV: Cups without screw holes showed a decreased risk of cup revision (implant exchange or removal) due to any reason at both 2 years (adjusted hazard ratio, HR: 0.6, confidence interval, CI: 0.5-0.8) and 10 years (HR: 0.7, CI: 0.5- 0.9). However, for aseptic loosening, there was no significant difference between cups with and without screw holes, with an implant survival rate of 99.9% (CI: 99.8-99.9) at 2 years and 99.1% (CI: 98.6-99.7) at 10 years.

    Conclusion: Uncemented cups augmented with screws, pegs, or hydroxyapatite do not have improved long-term stability compared with cups with press-fit only. Unsealed screw holes in uncemented cups appear to be a risk factor for the development of larger osteolytic lesions. CT showed three different types of osteolytic lesions. The risk of aseptic loosening for modern uncemented cup designs is very low, and cups without additional augmentation do not have an increased revision rate. In contrast, the risk of cup revision for any reason was higher for cups with screw holes. CT can be used for migration studies for the longitudinal evaluation of patients with tantalum markers with precision comparable to that of RSA.

  • 205.
    Otten, Volker T C
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Röhrl, Stephan M
    Nivbrant, Bo
    Nilsson, Kjell G
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Stability of Uncemented Cups - Long-Term Effect of Screws, Pegs and HA Coating: A 14-Year RSA Follow-Up of Total Hip Arthroplasty2016In: The Journal of Arthroplasty, ISSN 0883-5403, E-ISSN 1532-8406, Vol. 31, no 1, p. 156-161Article in journal (Refereed)
    Abstract [en]

    Screws, pegs and hydroxyapatite-coating are used to enhance the primary stability of uncemented cups. We present a 14-year follow-up of 48 hips randomized to four groups: press-fit only, press-fit plus screws, press-fit plus pegs and hydroxyapatite-coated cups. Radiostereometric migration measurements showed equally good stability regardless cup augmentation. The mean wear rate was high, 0.21mm/year, with no differences between the groups. Seven hips had radiographical osteolysis but only in hips with augmented cups. Cups without screw-holes compared with cups with screw-holes resulted in better clinical outcome at the 14-year follow-up. Thus, augmentation of uncemented cups with screws, pegs, or hydroxyapatite did not appear to improve the long-term stability compared with press-fit only.

  • 206.
    Otten, Volker T C
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Nilsson, Kjell G
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Kärrholm, Johan
    Uncemented cups with and without screw holes in primary THA: a Swedish Hip Arthroplasty Register study with 22725 hipsManuscript (preprint) (Other academic)
    Abstract [en]

    Background and purpose: Uncemented cups in total hip arthroplasty (THA) are often augmented with additional screws to enhance their primary stability. We investigated whether there is a difference in the risk for revision between cups with screw holes and cups without screw holes.

    Patients and methods: We analyzed the risk for cup revision of uncemented cups registered in the Swedish Hip Arthroplasty Register (SHAR) between 2000 and 2017 with respect to the presence of screw holes. Only patients with primary osteoarthritis (OA) were included. 22725 cups, including 12354 without screw holes and 10371 with screw holes, were evaluated. Revision rates at 2 and 10 years after the primary operation were analyzed.

    Results: At a median follow-up time of 3.4 (0-18) years, 459 cup revisions were reported. The main reasons for cup revision during the whole observations time were infection, 52% of all cup revisions, and dislocation, 26% of all cup revisions. The survival rate with cup revision due to aseptic loosening as endpoint was 99.9% (95% CI 99.8-99.9) at 2 years for both cups with and cups without screw holes, and the survival rates at 10 years were 99.5% (CI 99.3-99.7) and 99.1% (CI 98.6-99.5), respectively. Cups without screw holes showed a decreased risk of revision due to any reason at both 2 years (adjusted hazard ratio [HR] 0.6, CI 0.5-0.8) and 10 years (HR 0.7, CI 0.5-0.9).

    Interpretation: We found a very low revision rate for aseptic loosening with modern, uncemented cup designs. Cups with screw holes had an increased risk for revision due to any reason in patients with primary OA.

  • 207.
    Otten, Volker T C
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Nilsson, Kjell G
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Kärrholm, Johan
    Uncemented cups with and without screw holes in primary THA: a Swedish Hip Arthroplasty Register study with 22,725 hips2019In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 90, no 3, p. 258-263Article in journal (Refereed)
    Abstract [en]

    Background and purpose — Uncemented cups in total hip arthroplasty (THA) are often augmented with additional screws to enhance their primary stability. We investigated whether there is a difference in the risk for revision between cups with screw holes and cups without screw holes.

    Patients and methods — We analyzed the risk for cup revision of uncemented cups registered in the Swedish Hip Arthroplasty Register (SHAR) between 2000 and 2017 with respe ct to the presence of screw holes. Only patients with primary osteoarthritis (OA) were included. 22,725 cups, including 12,354 without screw holes and 10,371 with screw holes, were evaluated. Revision rates at 2 and 10 years after the primary operation were analyzed.

    Results — At a median follow-up time of 3.4 years (0–18), 459 cup revisions were reported. The main reasons for cup revision during the whole observation time were infection, 52% of all cup revisions, and dislocation, 26% of all cup revisions. The survival rate with cup revision due to aseptic loosening as endpoint was 99.9% (95% CI 99.8–99.9) at 2 years for both cups with and cups without screw holes, and the survival rates at 10 years were 99.5% (CI 99.3–99.7) and 99.1% (CI 98.6–99.5), respectively. Cups without screw holes showed a decreased risk of revision due to any reason at both 2 years (adjusted hazard ratio [HR] 0.6, CI 0.5–0.8) and 10 years (HR 0.7, CI 0.5–0.9).

    Interpretation — We found a very low revision rate for aseptic loosening with modern, uncemented cup designs. Cups with screw holes had an increased risk of revision due to any reason in patients with primary OA

  • 208.
    Otten, Volker T C
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Stamenkov, Roumen
    Callary, Stuart A.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Howie, Donald W.
    Nilsson, Kjell G
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Osteolysis around uncemented cups withand without screw holes: Analysis of osteolytic lesions on CT images in 48 hips at a 14-year follow-upManuscript (preprint) (Other academic)
    Abstract [en]

    Osteolysis around uncemented cups is a major complication for THA. We present a 14-year follow-up of 48 hips previously randomized to four groups of cup fixation – sealed cups with press-fit only, cups with hydroxyapatite coating, cups with screws, and cups with pegs. CT scans revealed three types of osteolytic lesions – Type 1A (absence of trabecular bone and a sclerotic border), Type 1B (absence of trabecular bone without a sclerotic border), and Type 2 (reductions in radiodensity and trabeculae). Cups with screw-holes were surrounded with larger osteolytic lesions that were predominantly Type 1A. Unsealed screw holes in uncemented cups appeared to be a risk factor for osteolysis development. Modern CT scans reveal three types of osteolytic lesions. Distinction between types is important for comparability between studies.

  • 209.
    Parkkinen, Jyrki
    et al.
    Deparment of Pathology and Fornesic Medicine, University of Kuopio, Kuopio, Finlandd.
    Lammi, Mikko
    Deparment of Anatomy, University of Kuopio, Kuopio, Finlandd.
    Inkinen, Ritva
    Deparment of Anatomy, University of Kuopio, Kuopio, Finlandd.
    Jortikka, Matti
    Deparment of Anatomy, University of Kuopio, Kuopio, Finlandd.
    Tammi, Markku
    Deparment of Anatomy, University of Kuopio, Kuopio, Finlandd.
    Virtanen, Ismo
    Department of Anatomy, University of Helsinki, Helsinki, Finland.
    Helminen, Heikki
    Deparment of Anatomy, University of Kuopio, Kuopio, Finlandd.
    Influence of short-term hydrostatic pressure on organization of stress fibers in cultured chondrocytes.1995In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 13, no 4, p. 495-502, article id 7545746Article in journal (Refereed)
    Abstract [en]

    The present study describes changes in the organization of stress fibers that occur in articular cartilage chondrocytes subjected to hydrostatic pressure. Primary cultures of chondrocytes from bovine articular cartilage, grown on coverslips, were subjected to 5, 15, or 30 MPa hydrostatic pressure at 37 degrees C. The pressure was applied continuously or cyclically at two frequencies: 0.125 Hz (4 seconds of pressure and 4 seconds of no pressure) or 0.05 Hz (1 second of pressure and 19 seconds of no pressure) for a period of 2 hours. Control chondrocytes showed a polygonal form with prominent stress fibers extending across the cells. The exposure of cells to 30 MPa pressure caused a nearly total disappearance of stress fibers and retraction of the cells from each other. With pressure at 15 MPa or cyclic pressure, the number of cells with stress fibers was decreased. In cells subjected to 5 MPa pressure, the stress fibers resembled those in control chondrocytes. The pressure effects were reversible after 2 hours. Pressure had no effect on the staining pattern of vinculin, which suggests that microfilaments are more vulnerable to pressure than vinculin. The results indicate that cytoskeletal changes may be an integral part of the response of chondrocytes to hydrostatic pressure.

  • 210. Per-Henrik, Ågren
    et al.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Orthopaedics Sundsvall.
    Tullberg, Tycho
    Wretenberg, Per
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Orthopaedics Sundsvall.
    Factors affecting long-term treatment results of displaced intraarticular calcaneal fractures: a post hoc analysis of a prospective, randomized, controlled multicenter trial2014In: Journal of Orthopaedic Trauma, ISSN 0890-5339, E-ISSN 1531-2291, Vol. 28, no 10, p. 564-568Article in journal (Refereed)
    Abstract [en]

    Objectives: To study the factors affecting long-term treatment results of displaced intraarticular calcaneal fractures (DIACFs). Design: A post hoc analysis. Settings: Tertiary care teaching hospitals. Patients: Eight to twelve years of results from a randomized controlled multicenter trial of operative versus nonoperative treatment (n = 56) were divided into 2 groups: the superior 50% results (n = 28) and the inferior 50% results (n = 28), regardless of the treatment given. The determinant of this division was a visual analog score for pain and function. Interventions: The operative treatment consists of open reduction and internal fixation, whereas the nonoperative treatment consists of nonweight bearing and early range of motion exercise. Main Outcome Measurements: A visual analog score for pain and function, the short-form 36 (SF-36) general health outcome questionnaire, the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot scale, and Olerud-Molander score. We compared age, sex, fracture type (Sanders classification), treatment given, Böhler angle, residual articular surface step-off at healing, type of occupation, and injury insurance between the 2 groups. Results: Patients of the superior group had higher physical SF-36, AOFAS, and Olerud-Molander score than in the inferior group. Operative treatment, better Böhler angle and articular surface restoration, light labor/retirement, and absence of injury insurance were more common in the superior group. Age, sex, pretreatment Böhler angle, and fracture type were comparable in the superior and inferior groups. Conclusions: The decision making for definitive treatment of intraarticular calcaneal fractures is multifactorial with a spectrum of results and trends such as patient demographic features that should be considered in choosing the best treatment option.

  • 211.
    Persson, Frida
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Incidence and type of adverse events within 90 days after primary knee arthroplasty. - Evaluation of 363 patients operated 2013-2015 at the Department of Orthopedics, Umeå University Hospital.2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 212.
    Pettersson, Kurt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Whiplash injury: a clinical, radiographic and psychological investigation1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Whiplash injury is a common and troublesome disorder and approximately 10-40 per cent of its victims develop chronic symptoms. The annual incidence is estimated at 1/1000 inhabitants and the prevalence at 1%. The cause of chronic symptoms after whiplash injury is still unknown and no effective treatment has been presented so far.

    The present study is divided into two parts; the first part includes clinical, radiographic and psychological investigations, and the second part the effect of surgical intervention as well as intervention with medication.

    MRI studies (n=39) showed a larger proportion of pathologic findings compared to normal subjects, but no correlation with initial neurologic deficits was found. At the 2-year follow-up all patients with disc herniations with medullary impingement had persistent symptoms. Three patients had disc herniations that deteriorated from slight and moderate initial changes on the MRI to severe changes with medullary cord impingement. This deterioration might be a first sign of disc degeneration. Thus our results indicate that disc pathology is a contributing factor in the development of chronic symptoms.

    Measurements from standard lateral radiographs taken in neutral position were evaluated (n=48). A graphic digitizer connected to a microcomputer was used and the sagittal diameters were determined. Multivariate analysis of variance showed that the spinal canal was significantly smaller in patients with persistent symptoms indicating that a narrow spinal canal is unfavourable in patients subjected to whiplash injury.

    A psychological investigation (n=70) revealed no relationship between pre-existing personality traits and persistent symptoms. In our study, whiplash patients showed no differences in personality traits compared to normal controls.

    Our results after discectomy and anterior cervical fusion (n=20) because of chronic symptoms after whiplash injury were not satisfactory. We noticed that about half of the cases had less headache and neck pain but no beneficial effects on radicular pain, vertigo, visual and auditory symptoms were observed. Based on the criteria of a surgical evaluation, two patients were classified as good, nine as fair and nine as poor.

    A prospective randomised double-blind study of high-dose methyl-prednisolone compared to placebo was conducted (n=40). A clinical follow-up with repeated neurological examinations and a standardised questionnaire including VAS-scales and a pain sketch form were used for the evaluation of initial symptoms, before drug administration and at the follow-ups at 2 weeks, 6 weeks, and 6 months after the injury. At the 6-month follow-up there was a significant difference between the actively treated patients and placebo concerning disabling symptoms defined as inability to return to previous work, number of sick-days and sick-leave profile. All the actively treated patients had returned to work and none had multiple symptoms though three of them complained of intermittent neck pain. Our conclusion is therefore that acute treatment with high-dose corticosteroids might be beneficial to the prevention of disabling symptoms after whiplash injury.

  • 213.
    Pettersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Benmassa hos kvinnliga löpare med menstruationsrubbningar1997In: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, Vol. 6, no 2, p. 30-32Article in journal (Other academic)
  • 214.
    Pettersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bone mass in the young athlete1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bone mass and bone size accumulate during childhood and adolescence and peak in the twenties. The obtained peak bone mass has been suggested to be a major determinant of bone mass even in the very elderly. Although, genetic factors are the main determinants, environmental and lifestyle factors also play a crucial role in modulating maximal bone mass. Assessing these lifestyle factors would be of great importance for the intervention strategies against osteoporosis.  

    The first aim of this thesis was to compare the bone mass and bone size in male and female young adults on a high level of physical activity with males or females on a low level of physical activity. Furthermore, it also aimed to investigate the influence of pubertal maturity, menstrual disturbances, and different body constitutional factors on bone mass and size during adolescence and young adulthood.  

    The female activity groups consisted of cross-county skiers, soccer players, and rope skippers. Compared to their age-matched inactive controls, all these athletic groups demonstrated a significantly higher bone mineral density (BMD) at those sites subjected to the sport-specific loading. Rope-skipping, a very high impact activity was associated with a higher bone size, preferentially in the lower extremity, suggesting an effect of weight-bearing activity also on bone geometry. The effect of menstrual disturbances was evaluated in a group of long-distance runners, where amenorrheic runners had significantly lower BMD in both trabecular and also cortical bone in the lower extremity compared to eumenorrheic runners, suggesting that weight-bearing activity cannot compensate for the shortfall of reduced estrogen levels.  

    The male activity groups consisted of ice hockey players and badminton players. Compared to their age-matched controls, both athletic groups demonstrated a significantly higher BMD at those sites subjected to the sport-specific loading. Especially badminton was associated with a high BMD, suggesting that physical activity, including jumps in unusual directions has a great osteogenic potential.  

    The main determinants of BMD in both male and females were, except for type of physical activity, activity, muscle strength, height, and different body constitutional factors. However, the relationships with muscle strength and body constitution were somewhat weaker in the athletic groups, especially in the males, indicating that impact forces may be of greater importance in regulating bone mass in highly trained athletes. Yet bone size was largely determined by parameters related to body size and less strongly to physical activity. In a prospective study on adolescent boys, the changes in bone mass during late puberty were mainly accounted for by growth and development, including height and pubertal maturation, and less to physical activity level. Thus, the osteogenic effect from physical activity seems to be of importance for bone mass achievement predominantly before late puberty.

  • 215.
    Pettersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Fysisk aktivitet hos ungdomar och framtida risk för besnkörhet.2000In: Svensk Idrottsmedicin, ISSN 1103-7652, no 1, p. 7-9Article in journal (Other academic)
  • 216.
    Pettersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Styrketräning och påvarkan av benmassa2001In: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, Vol. 10, no 3, p. 38-42Article in journal (Other academic)
  • 217.
    Pettersson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nilsson, Martin
    Institutionen för Internmedicin, Sahlgrenska Universitetssjukhus.
    Sundh, Valter
    Institutionen för Geriatrik, Sahlgrenska Universitetssjukhus.
    Mellström, Dan
    Göteborgs universitet och Institutionen för Internmedicin, Sahlgrenska Universitetssjukhus.
    Lorentzon, Mattias
    Göteborgs universitet och Institutionen för Internmedicin, Sahlgrenska Universitetssjukhus.
    Physical activity is the strongest predictor of calcaneal peak bone mass in young Swedish men2010In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 21, no 3, p. 447-455Article in journal (Refereed)
    Abstract [en]

    In a highly representative sample of young adult Swedish men (n = 2,384), we demonstrate that physical activity during childhood and adolescence was the strongest predictor of calcaneal bone mineral density (BMD), and that peak bone mass was reached at this site at the age of 18 years.

    INTRODUCTION: The purpose of the present study was to determine if physical activity during growth is associated with peak calcaneal BMD in a large, highly representative cohort of young Swedish men.

    METHODS: In this study, 2,384 men, 18.3 +/- 0.3 (mean +/- SD) years old, were included from a population attending the mandatory tests for selection to compulsory military service in Sweden. BMD (g/cm(2)) of the calcaneus was measured using dual-energy X-ray absorptiometry. Training habits were investigated using a standardized questionnaire.

    RESULTS: Regression analysis (with age, height, weight, smoking, and calcium intake as covariates) demonstrated that history of regular physical activity was the strongest predictor and could explain 10.1% of the variation in BMD (standardized beta = 0.31, p < 0.001). A regression model with quadratic age effect revealed maximum BMD at 18.4 years.

    CONCLUSIONS: We found that history of physical activity during growth was the strongest predictor of peak calcaneal BMD in young men.

  • 218.
    Pettersson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Lorentzon, R
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    A comparison of bone mineral density and muscle strength in young male adults with different exercise level.1999In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 64, no 6, p. 490-8Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate any differences in bone mass at different sites between young adults subjected to a high physical activity and a group of young adults with a low level of physical activity. In addition, we compared the relationship among bone mass, muscle strength, and body constitution in these two groups. The reference group consisted of 20 men, age 24.6 +/- 2.3 years, not training for more than 3 hours per week. The ice hockey players consisted of 20 players, age 23.4 +/- 4.9 years, from an ice hockey team in the second highest national Swedish league, training for about 10 hours per week. The groups were matched according to age, height, and weight. Areal bone mineral density (BMD) was measured in total body, head, humerus, spine, pelvis, femur, femoral neck, Ward's triangle, trochanter, femur diaphysis, proximal tibia, and tibia diaphysis using dual energy X-ray absorptiometry. BMD was significantly higher in the total body (8.1%), humerus (11.4%), spine (12.7%), pelvis (12.4%), femoral neck (10.3%), femur (7.4%), proximal tibia (9.8%), and tibia diaphysis (7.5%) in the high activity group. Fat mass was significantly lower in the high activity group (18.7%). The high activity group also had a significantly higher lean body mass (5.4%) and a significantly higher isokinetic muscle strength of the quadriceps muscle compared with the reference group. In the reference group, there was a general strong independent relationship between muscle strength of the thigh and all BMD sites, except for the head, tibia diaphysis, and proximal tibia. Furthermore, in the same group, body mass index (BMI) independently predicted pelvis BMD. On the contrary, in the high activity group, muscle strength did not predict any BMD site at all. In the same group, body constitutional parameters (weight, height, and fat mass) independently predicted pelvis BMD, and BMI was shown to be an independent predictor of humerus BMD. The differences in BMD between the groups seem to be site-specific and may be associated with the type and magnitude of loading during off season training and preferentially during ice hockey. High physical activity seems to weaken the relationship between BMD and muscle strength. Hence, impact forces may be of greater importance in regulating bone mass than muscle strength in itself in highly trained athletes.

  • 219. Petursson, Gunnar
    et al.
    Fenstad, Anne Marie
    Gøthesen, Øystein
    Haugan, Kristin
    Dyrhovden, Gro Sævik
    Hallan, Geir
    Röhrl, Stephan M
    Aamodt, Arild
    Nilsson, Kjell G
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Furnes, Ove
    Similar migration in computer-assisted and conventional total knee arthroplasty.2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 2, p. 166-172Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Computer-assisted surgery (CAS) in total knee arthroplasty (TKA) has been used in recent years in the hope of improving the alignment and positioning of the implant, thereby achieving a better functional outcome and durability. However, the role of computer navigation in TKA is still under debate. We used radiostereometric analysis (RSA) in a randomized controlled trial (RCT) to determine whether there are any differences in migration of the tibial component between CAS- and conventionally (CONV-) operated TKA. Patients and methods - 54 patients (CAS, n = 26; CONV, n = 28) with a mean age of 67 (56-78) years and with osteoarthritis or arthritic disease of the knee were recruited from 4 hospitals during the period 2009-2011. To estimate the mechanical stability of the tibial component, the patients were examined with RSA up to 24 months after operation. The following parameters representing tibial component micromotion were measured: 3-D vector of the prosthetic marker that moved the most, representing the magnitude of migration (maximum total point motion, MTPM); the largest negative value for y-translation (subsidence); the largest positive y-translation (lift-off); and prosthetic rotations. The precision of the RSA measurements was evaluated and migration in the 2 groups was compared. Results - Both groups had most migration within the first 3 months, but there was no statistically significant difference in the magnitude of the migration between the CAS group and the CONV group. From 3 to 24 months, the MTPM (in mm) was 0.058 and 0.103 (p = 0.1) for the CAS and CON groups, respectively, and the subsidence (in mm) was 0.005 and 0.011 (p = 0.3). Interpretation - Mean MTPM, subsidence, lift-off, and rotational movement of tibial trays were similar in CAS- and CONV-operated knees.

  • 220.
    Piltti, Juha
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bygdell, Joakim
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fernández-Echevarría, Cecilia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Marcellino, Daniel
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China.
    Rho-kinase inhibitor Y-27632 and hypoxia synergistically enhance chondrocytic phenotype and modify S100 protein profiles in human chondrosarcoma cells2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3708Article in journal (Refereed)
    Abstract [en]

    Articular chondrocytes are slowly dividing cells that tend to lose their cell type-specific phenotype and ability to produce structurally and functionally correct cartilage tissue when cultured. Thus, culture conditions, which enhance the maintenance of chondrocyte phenotype would be very useful for cartilage research. Here we show that Rho-kinase inhibition by Y-27632 under hypoxic conditions efficiently maintains and even enhances chondrocyte-specific extracellular matrix production by chondrocytic cells. The effects of long-term Y-27632 exposure to human chondrosarcoma 2/8 cell phenotype maintenance and extracellular matrix production were studied at normoxia and at a 5% low oxygen atmosphere. Y-27632 treatment at normoxia induced ACAN and COL2A1 gene up-regulation and a minor increase of sulfated glycosaminoglycans (sGAGs), while type II collagen expression was not significantly up-regulated. A further increase in expression of ACAN and COL2A1 was achieved with Y-27632 treatment and hypoxia. The production of sGAGs increased by 65.8%, and ELISA analysis revealed a 6-fold up-regulation of type II collagen. Y-27632 also induced the up-regulation of S100-A1 and S100-B proteins and modified the expression of several other S100 protein family members, such as S100-A4, S100-A6, S100-A13 and S100-A16. The up-regulation of S100-A1 and S100-B proteins is suggested to enhance the chondrocytic phenotype of these cells.

  • 221.
    Prittinen, Juha O.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ylärinne, Janne H.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Piltti, Juha
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effect of gravitational force and hydrostatic pressure on the development of articular neocartilage2017In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, p. S386-S386Article in journal (Other academic)
  • 222.
    Prittinen, Juha
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ylärinne, Janne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Piltti, Juha
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Nordlab Kokkola, Keski-Pohjanmaa Central Hospital Soite, Kokkola, Finland.
    Karhula, Sakari S.
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland; Infotech Doctoral Program, University of Oulu, Oulu, Finland.
    Rieppo, Lassi
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
    Ojanen, S. P.
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland; Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Korhonen, Rami K.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Saarakkala, S.
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an Jiaotong University, Xi'an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effect of centrifugal force on the development of articular neocartilage with bovine primary chondrocytes2019In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 375, no 3, p. 629-639Article in journal (Refereed)
    Abstract [en]

    A lot has been invested into understanding how to assemble cartilage tissue in vitro and various designs have been developed to manufacture cartilage tissue with native-like biological properties. So far, no satisfactory design has been presented. Bovine primary chondrocytes are used to self-assemble scaffold-free constructs to investigate whether mechanical loading by centrifugal force would be useful in manufacturing cartilage tissue in vitro. Six million chondrocytes were laid on top of defatted bone disks placed inside an agarose well in 50-ml culture tubes. The constructs were centrifuged once or three times per day for 15 min at a centrifugal force of 771×g for up to 4 weeks. Control samples were cultured under the same conditions without exposure to centrifugation. The samples were analysed by (immuno)histochemistry, Fourier transform infrared imaging, micro-computed tomography, biochemical and gene expression analyses. Biomechanical testing was also performed. The centrifuged tissues had a more even surface covering a larger area of the bone disk. Fourier transform infrared imaging analysis indicated a higher concentration of collagen in the top and bottom edges in some of the centrifuged samples. Glycosaminoglycan contents increased along the culture, while collagen content remained at a rather constant level. Aggrecan and procollagen α1(II) gene expression levels had no significant differences, while procollagen α2(I) levels were increased significantly. Biomechanical analyses did not reveal remarkable changes. The centrifugation regimes lead to more uniform tissue constructs, whereas improved biological properties of the native tissue could not be obtained by centrifugation.

  • 223.
    Pulkkinen, Hertta
    et al.
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammentausta, Eveliina
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Laasanen, Mikko
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Hämäläinen, Eija-Riitta
    Bioprocess Engineerng Laboratory, Department of Process and Environmental Engineering, University of Oulu, Oulu, Finland.
    Kiviranta, Ilkka
    Jyväskylä Central Hospital, Jyväskylä, Finland.
    Lammi, Mikko
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Cellulose sponge as a scaffold for cartilage tissue engineering.2006In: Bio-medical materials and engineering, ISSN 0959-2989, E-ISSN 1878-3619, Vol. 16, no 4 Suppl, p. S29-S35, article id 16823110Article in journal (Refereed)
    Abstract [en]

    One goal of functional tissue engineering is to manufacture scaffolds infiltrated with chondrocytes which are suitable for transplantation into the lesion areas of articular cartilage. Various research strategies are used to fabricate cartilage transplants which would have the correct phenotype, contain enough extracellular matrix components, and have structural and biomechanical properties equivalent to normal articular cartilage. We have investigated the suitability of viscose cellulose sponges as a scaffold for cartilage tissue engineering. The sponges were tested alone, or with recombinant human type II collagen cross-linked inside the material. Scanning electron microscopy and confocal microscopy were used to study the structure of the scaffold during four weeks of cultivation. Cellulose and cellulose/recombinant type II collagen sponges were biocompatible for at least four weeks in cultivation, and gradual filling of the scaffold was observed. However, the constructs remained soft during the observation period, and were devoid of extracellular matrix composition typical for normal articular cartilage.

  • 224.
    Pulkkinen, Hertta
    et al.
    Institute of Biomedicine, Anatomy, University of Eastern Finland, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, Anatomy, University of Eastern Finland, Kuopio, Finland.
    Valonen, Pia
    Institute of Biomedicine, Anatomy, University of Eastern Finland, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Orthopaedics and Traumatology, University of Helsinki, Helsinki, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Engineering of cartilage in recombinant human type II collagen gel in nude mouse model in vivo.2010In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 18, no 8, p. 1077-1087, article id 20472086Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Our goal was to test the recombinant human type II collagen (rhCII) material as a gel-like scaffold for chondrocytes in a nude mouse model in vivo.

    DESIGN: Isolated bovine chondrocytes (6x10(6)) were seeded into rhCII gels (rhCII-cell) and injected subcutaneously into the backs of nude mice. For comparison, chondrocytes (6x10(6)) in culture medium (Med-cell) and cell-free rhCII gels (rhCII-gel) were similarly injected (n=24 animals, total of three injections/animal). After 6 weeks, the tissue constructs were harvested and analyzed.

    RESULTS: Chondrocytes with or without rhCII-gel produced white resilient tissue, which in histological sections had chondrocytes in lacunae-like structures. Extracellular matrix stained heavily with toluidine blue stain and had strongly positive collagen type II immunostaining. The tissue did not show any evidence of vascular invasion or mineralization. The cell-free rhCII-gel constructs showed no signs of cartilage tissue formation. Cartilage tissue produced by Med-cell was thin and macroscopically uneven, while the rhCII-cell construct was smooth and rounded piece of neotissue. RhCII-cell constructs were statistically thicker than Med-cell ones. However, no statistical differences were found between the groups in terms of glycosaminoglycan (GAG) content or biomechanical properties.

    CONCLUSIONS: These results show that rhCII-gel provides good expansion and mechanical support for the formation of cartilage neotissue. RhCII material may allow favorable conditions in the repair of chondral lesions.

  • 225.
    Pulkkinen, Hertta
    et al.
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Valonen, Piia
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Hämäläinen, Eija-Riitta
    Bioprocess Engineering Laboratory, University of Oulu, Oulu, Finland.
    Lammi, Mikko
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland; Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland; Department of Orthopaedics and Traumatology, Helsinki University Hospital, Helsinki, Finland.
    Recombinant human type II collagen as a material for cartilage tissue engineering.2008In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 31, no 11, p. 960-969, article id 19089798Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Collagen type II is the major component of cartilage and would be an optimal scaffold material for reconstruction of injured cartilage tissue. In this study, the feasibility of recombinant human type II collagen gel as a 3-dimensional culture system for bovine chondrocytes was evaluated in vitro.

    METHODS: Bovine chondrocytes (4x106 cells) were seeded within collagen gels and cultivated for up to 4 weeks. The gels were investigated with confocal microscopy, histology, and biochemical assays.

    RESULTS: Confocal microscopy revealed that the cells maintained their viability during the entire cultivation period. The chondrocytes were evenly distributed inside the gels, and the number of cells and the amount of the extracellular matrix increased during cultivation. The chondrocytes maintained their round phenotype during the 4-week cultivation period. The glycosaminoglycan levels of the tissue increased during the experiment. The relative levels of aggrecan and type II collagen mRNA measured with realtime polymerase chain reaction (PCR) showed an increase at 1 week.

    CONCLUSION: Our results imply that recombinant human type II collagen is a promising biomaterial for cartilage tissue engineering, allowing homogeneous distribution in the gel and biosynthesis of extracellular matrix components.

  • 226.
    Pulkkinen, Hertta
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Valonen, Piia
    A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Rieppo, Lassi
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Silvast, Tuomo
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Orthopaedics and Traumatology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Repair of osteochondral defects with recombinant human type II collagen gel and autologous chondrocytes in rabbit2013In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 21, no 3, p. 481-490, article id 23257243Article in journal (Refereed)
    Abstract [en]

    Summary

    Objective

    Recombinant human type II collagen (rhCII) gels combined with autologous chondrocytes were tested as a scaffold for cartilage repair in rabbits in vivo.

    Method

    Autologous chondrocytes were harvested, expanded and combined with rhCII-gel and further pre-cultivated for 2 weeks prior to transplantation into a 4 mm diameter lesion created into the rabbit's femoral trochlea (n = 8). Rabbits with similar untreated lesions (n = 7) served as a control group.

    Results

    Six months after the transplantation the repair tissue in both groups filled the lesion site, but in the rhCII-repair the filling was more complete. Both repair groups also had high proteoglycan and type II collagen contents, except in the fibrous superficial layer. However, the integration to the adjacent cartilage was incomplete. The O'Driscoll grading showed no significant differences between the rhCII-repair and spontaneous repair, both representing lower quality than intact cartilage. In the repair tissues the collagen fibers were abnormally organized and oriented. No dramatic changes were detected in the subchondral bone structure. The repair cartilage was mechanically softer than the intact tissue. Spontaneously repaired tissue showed lower values of equilibrium and dynamic modulus than the rhCII-repair. However, the differences in the mechanical properties between all three groups were insignificant.

    Conclusion

    When rhCII was used to repair cartilage defects, the repair quality was histologically incomplete, but still the rhCII-repairs showed moderate mechanical characteristics and a slight improvement over those in spontaneous repair. Therefore, further studies using rhCII for cartilage repair with emphasis on improving integration and surface protection are required.

  • 227.
    Pulliainen, Outi
    et al.
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Vasara, Anna
    Department of Orthopaedics, Helsinki University Hospital, Peijas Hospital, Vantaa, Finland.
    Hyttinen, Mika
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Tiitu, Virpi
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Valonen, Piia
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Kellomäki, Minna
    Institute of Biomaterials, Tampere University of Technology, Tampere, Finland.
    Jurvelin, Jukka
    Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Physics, University of Kuopio, Kuopio, Finland.
    Peterson, Lars
    Department of Orthopaedics, Göteborg University, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lindahl, Anders
    Institute of Laboratory Medicine, Department of Clinical Chemistry and Transfusion Medicine, Göteborg University, Göteborg, Sweden; Sahlgrenska University Hospital, Göteborg, Sweden.
    Kiviranta, Ilkka
    Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Poly-L-D-lactic acid scaffold in the repair of porcine knee cartilage lesions.2007In: Tissue engineering, ISSN 1076-3279, E-ISSN 1557-8690, Vol. 13, no 6, p. 1347-1355, article id 17518746Article in journal (Refereed)
    Abstract [en]

    Articular cartilage injuries cause a major clinical problem because of the negligible repair capacity of cartilage. Autologous chondrocyte transplantation is a surgical method developed to repair cartilage lesions. In the operation, cartilage defect is covered with a periosteal patch and the suspension of cultured autologous chondrocytes is injected into the lesion site. The method can form good repair tissue, but new techniques are needed to make the operation easier and to increase the postoperative biomechanical properties of the repair tissue. In this study, we investigated poly-L,D-lactic acid (PLDLA) scaffolds alone or seeded with autologous chondrocytes in the repair of circular 6-mm cartilage lesions in immature porcine knee joints. Spontaneous repair was used as a reference. Histologic evaluation of the repair tissue showed that spontaneous repair exhibited higher scores than either PLDLA scaffold group (with or without seeded chondrocytes). The scaffold material was most often seen embedded in the subchondral bone underneath the defect area, probably because of the hardness of the PLDLA material. However, some of the cell-seeded and nonseeded scaffolds contained cartilaginous tissue, suggesting that invasion of mesenchymal cells inside nonseeded scaffolds had occurred. Hyaluronan deposited in the scaffold had possibly acted as a chemoattractant for the cell recruitment. In conclusion, the PLDLA scaffold material used in this study was obviously mechanically too hard to be used for cartilage repair in immature animals.

  • 228.
    Puustjärvi, Kaija
    et al.
    Deaprtment of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Deaprtment of Anatomy, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Deaprtment of Anatomy, University of Kuopio, Kuopio, Finland.
    Inkinen, Ritva
    Deaprtment of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Deaprtment of Anatomy, University of Kuopio, Kuopio, Finland.
    Proteoglycans in the intervertebral disc of young dogs following strenuous running exercise.1994In: Connective Tissue Research, ISSN 0300-8207, E-ISSN 1607-8438, Vol. 30, no 3, p. 225-240, article id 8039389Article in journal (Refereed)
    Abstract [en]

    The proteoglycans (PGs) of intervertebral disc were studied in ten beagles which ran on a treadmill for one year (up to 40 km/day) and in ten non-running control dogs. Nucleus pulposus and annulus fibrosus from cervical (C5) and thoracic (T6 and T12) discs were labeled in vitro with 35SO4. The extractability, concentration and synthesis of PGs, and the electrophoretic subpopulations, aggregation and glycosaminoglycan chain lengths of newly-synthesized and total PGs were measured. Sulfate incorporation was significantly elevated by running in the C5 disc and reduced in the annulus of T6 discs. In the annulus of the T6 discs the concentration of total PGs was significantly lower although that of dermatan sulfate PGs was actually higher than in the controls. The results show that enhanced loading of the spine exerts significant alterations in the intervertebral disc PGs in a spine-level specific manner. In the most strained area of the spine (upper thoracic), the alterations in the runners suggest compromised biomechanical properties of the disc.

  • 229.
    Puustjärvi, Kaija
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Surgery, Kuopio, University Hospital, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Flat bed scanner in the quantitative assay of 35SO4-incorporation by X-ray film autoradiography of intervertebral disc sections.1993In: Histochemistry, ISSN 0301-5564, Vol. 99, no 1, p. 67-73, article id 8468196Article in journal (Refereed)
    Abstract [en]

    A rapid quantitation of proteoglycan synthesis distribution in intervertebral disc and endplates is described. Tissue blocks of disc (C7-Th1) in the midsagittal plane from ten female beagles were incubated in the presence of 35SO4 and prepared as histological slides. For comparison, sulphate incorporation rates in the C5-C6 discs were assayed by liquid scintillation. Autoradiographic film exposed against the labelled sections was developed and digitized for image analysis using a 256 grey level flat bed table scanner connected to a microcomputer. The film density versus dpm (disintegrations per minute) calibration was performed using a set of 35SO4-labelled glycosaminoglycan standards applied on the same film. Since section thickness, dpm calibration of the film density and the specific activity of sulphate in the medium were known, the incorporations per tissue volume could be calculated. The average incorporation rates of the anterior and posterior annulus fibrosus, nucleus pulposus and vertebral endplates were 5.2 +/- 0.9, 5.2 +/- 0.8, 4.5 +/- 0.6 and 4.1 +/- 0.8 pmol/mm3 per h (+/- SE, n = 10), respectively and closely corresponded to those obtained by liquid scintillation. This method offers a convenient and reproducible way to measure the rate of proteoglycan synthesis in large tissue sections but also in thin cartilaginous tissues such as the vertebral endplate.

  • 230.
    Puustjärvi, Kaija
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Surgery, Kuopio University Hospital, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Proteoglycan synthesis in canine intervertebral discs after long-distance running training.1993In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 11, no 5, p. 738-746, article id 8410474Article in journal (Refereed)
    Abstract [en]

    The alterations and distribution of proteoglycan (PG) synthesis in the intervertebral discs of young dogs exercised with long-distance running (40 km/day) were studied with a method based on image analysis of tissue sections. Ten dogs were run on a treadmill daily for 55 weeks, and 10 dogs from the same litters served as controls. The daily running distance gradually was increased to 40 km and was maintained at that level for the final 15 weeks. Midsagittal disc segments C7-T1, T8-9, and L1-2 were labeled with 35SO4, and histological sections of the segments were apposed against autoradiographic film to determine the synthesis of PGs. Next, the same sections were stained with safranin O to estimate possible alterations in PG concentration. The radiographs and stained sections were digitized with a flatbed scanner and measured by image analysis. The lumbar discs of runners displayed a significantly lower rate of 35SO4 incorporation, while a tendency toward enhanced incorporation was seen in the cervical and thoracic discs. Safranin O staining showed a pattern just opposite to 35SO4 incorporation: decreased staining in the cervical and thoracic discs and increased staining in the lumbar discs of the runners. The results demonstrate qualitatively different influences of long-term running training on PG metabolism at the cervical, thoracic, and lumbar levels in young dogs.

  • 231.
    Pöllänen, Raimo
    et al.
    BioMater Center, University of Eastern Finland, Kuopio, Finland.
    Tikkanen, Anna-Maria
    BioMater Center, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biomedicine, University of Eastern Finland, Kuopio, Finland; Department of Biosciences, Applied Biotechnology, University of Eastern Finland, Kuopio, Finland.
    Lappalainen, Reijo
    BioMater Center, University of Eastern Finland, Kuopio, Finland; Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    The effect of loading and material on the biomechanical properties and vitality of bovine cartilage in vitro.2011In: Journal of Applied Biomaterials and Biomechanics, ISSN 1722-6899, Vol. 9, no 1, p. 47-53, article id 21445828Article in journal (Refereed)
    Abstract [en]

    PURPOSE: New methodology for long-term (270 h) biomechanical testing with living cartilage was developed. Polyurethane (PU) implant material was compared with stainless steel and reference samples in static unconfined compressive loading conditions on cartilage to provide a basis for dynamic testing of novel PU implant materials under conditions that simulate an articulating human knee joint.

    METHODS: Custom-made tools and techniques were developed to prepare cylindrical samples from bovine patella with cartilage including subchondral bone. Specific incubator cups with static loading setups for a culture incubator were manufactured to keep bovine cartilage explants alive in cell culture conditions under unconfined static compressive loading (0.25 MPa) for 270 h (11.25 d). Four loading conditions of cartilage were studied: free (FREE), restrained minimal loading (RESTR), loading with a metal plate (MEW) and loading with polyurethane (PUW).

    RESULTS: After static loading for 270 h, cartilage biomechanical tests indicated clear differences between the groups in frequency dependent dynamic stiffness curves. Surprisingly, the PU curves were closest to the FREE sample curves. Those with load and direct contact with metal (MEW) became significantly stiffer, while restrained samples became softer. Significant differences (p<0.05, Mann-Whitney's U test) in cell vitality between samples from various groups could be seen in fluorescein diacetate (FDA) and propidium iodide (PI) stained samples by confocal microscopic analysis. The approximate mean percentages of living cells after 270 hours cultivation were: FREE 87%, MEW 3%, PUW 35%, and RESTR 66%. Test results indicate that it is possible to keep cartilage cells alive in cell culture incubator conditions for two weeks period under a 0.25 MPa unconfined static loading. The FREE samples were most successful and cells loaded with PU were more vital than cells loaded with metal.

    CONCLUSIONS: Based on the results, PU seems to be more compatible material than surgical steel in contact with living cartilage. Because of a large variation in the quality of bovine cartilage material from different animals, special care is necessary when selecting specimens to guarantee reliable and reproducible results.

  • 232.
    Qu, Chengjuan
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Hirviniemi, Mikko
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Effects of freeze-thaw cycle with and without proteolysis inhibitors and cryopreservant on the biochemical and biomechanical properties of articular cartilage2014In: Cartilage, ISSN 1947-6035, E-ISSN 1947-6043, Vol. 5, no 2, p. 97-106, article id 26069689Article in journal (Refereed)
    Abstract [en]

    Objective: We investigated the effects of freeze-thawing on the properties of articular cartilage. Design: The reproducibility of repeated biomechanical assay of the same osteochondral sample was first verified with 11 patellar plugs from 3 animals. Then, 4 osteochondral samples from 15 bovine patellae were divided into 4 groups. The reference samples were immersed in phosphate-buffered saline (PBS) containing proteolysis inhibitors and biomechanically tested before storage for further analyses. Samples of group 1 were biomechanically tested before and after freeze-thawing in PBS in the absence and those of group 2 in the presence of inhibitors. Samples of the group 3 were biomechanically tested in PBS-containing inhibitors, but frozen in 30% dimethyl sulfoxide/PBS and subsequently tested in PBS supplemented with the inhibitors. Glycosaminoglycan contents of the samples and immersion solutions were analyzed, and proteoglycan structures examined with SDS-agarose gel electrophoresis. Results: Freeze-thawing decreased slightly dynamic moduli in all 3 groups. The glycosaminoglycan contents and proteoglycan structures of the cartilage were similar in all experimental groups. Occasionally, the diffused proteoglycans were partly degraded in group 1. Digital densitometry revealed similar staining intensities for the glycosaminoglycans in all groups. Use of cryopreservant had no marked effect on the glycosaminoglycan loss during freeze-thawing. Conclusion: The freeze-thawed cartilage samples appear suitable for the biochemical and biomechanical studies.

  • 233.
    Qu, Cheng-Juan
    et al.
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Jauhiainen, Marjo
    Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.
    Auriola, Seppo
    Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Effects of glucosamine sulfate on intracellular UDP-hexosamine and UDP-glucuronic acid levels in bovine primary chondrocytes.2007In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 15, no 7, p. 773-779, article id 17320421Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To analyze the effects of exogenously added glucose (Glc), glucosamine (GlcN) and glucosamine sulfate (GS) on the intracellular UDP-hexoses (UDP-Hex), UDP-N-acetylhexosamines (UDP-HexN) and UDP-glucuronic acid (UDP-GlcA) levels in bovine primary chondrocytes.

    METHODS: Chondrocytes were incubated with different concentrations of Glc, GlcN and GS either in high- or low-glucose DMEM for up to 120min to analyze the intracellular levels of UDP-Hex, UDP-GlcA and UDP-HexN by a reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry analysis. Glycosaminoglycan (GAG) synthesis rate and aggrecan mRNA expression levels were quantified using (35)S-sulfate incorporation assay and quantitative real-time RT-PCR, respectively. The cells were cultivated for 2 days or 8 days before UDP-sugar analysis.

    RESULTS: Levels of UDP-HexN and UDP-GlcA were unchanged at 10microM concentration of GS in low-glucose DMEM, while addition of 1mM GlcN or GS in low-glucose DMEM for 10min increased UDP-HexN level. The highest intracellular level of UDP-HexN was reached at 30min after addition of 1mM GS to the cells. The intracellular contents of UDP-HexN and UDP-GlcA related to UDP-Hex were higher after prolonged cultivation of chondrocytes for 8 days compared with 2-day-old cultures. Aggrecan mRNA expression and GAG synthesis remained at control level after the cells were treated with 10, 100microM or 1mM of GS for 24h.

    CONCLUSION: Physiologically relevant level of GS could not increase the intracellular UDP-HexN and UDP-GlcA levels in bovine primary chondrocyte, while longer-time culture itself appeared to increase the intracellular UDP-HexN and UDP-GlcA levels.

  • 234.
    Qu, Cheng-Juan
    et al.
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Karjalainen, Hannu
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    The lack of effect of glucosamine sulphate on aggrecan mRNA expression and (35)S-sulphate incorporation in bovine primary chondrocytes.2006In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1762, no 4, p. 453-459, article id 16504489Article in journal (Refereed)
    Abstract [en]

    Glucosamine and glucosamine sulphate have been promoted as a disease-modifying agent to improve the clinical symptoms of osteoarthritis. The precise mechanism of the action of the suggested positive effect of glucosamine or glucosamine sulphate on cartilage proteoglycans is not known, since the level of glucosamine in plasma remains very low after oral administration of glucosamine sulphate. We examined whether exogenous hexosamines or their sulphated forms would increase steady-state levels of aggrecan and hyaluronan synthase (HAS) or glycosaminoglycan synthesis using Northern blot and (35)S-sulphate incorporation analyses. Total RNA was extracted from bovine primary chondrocytes which were cultured either in 1 mM concentration of glucosamine, galactosamine, mannosamine, glucosamine 3-sulphate, glucosamine 6-sulphate or galactosamine 6-sulphate for 0, 4, 8 and 24 h, or in three different concentrations (control, 100 microM and 1 mM) of glucosamine sulphate salt or glucose for 24 or 72 h. Northern blot assay showed that neither hexosamines nor glucosamine sulphate salt stimulated aggrecan and HAS-2 mRNA expression. Glycosaminoglycan synthesis remained at a control level in the treated cultures, with the exception of mannosamine which inhibited (35)S-sulphate incorporation in low-glucose DMEM treatment. In our culture conditions, hexosamines or their sulphated forms did not increase aggrecan expression or (35)S-sulphate incorporation.

  • 235.
    Qu, Chengjuan
    et al.
    Department of Biosciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Lindeberg, Heli
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland.
    Ylärinne, Janne
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Five percent oxygen tension is not beneficial for neocartilage formation in scaffold-free cell cultures2012In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 348, no 1, p. 109-117, article id 22392735Article in journal (Refereed)
    Abstract [en]

    We have investigated whether 5% oxygen tension (O(2)) is beneficial for neocartilage formation when chondrocytes are cultured in transwell-COL inserts. Six million bovine primary chondrocytes were cultured in an insert with DMEM supplemented with 10% fetal bovine serum and antibiotics, with or without glucosamine sulphate (GS) in a 5% or 20% O(2) environment for 2, 4, or 6 weeks. The samples were collected for the histological staining of proteoglycans (PGs) and type II collagen, quantitative reverse transcription with the polymerase chain reaction (RT-PCR) analyses of the mRNA expression of aggrecan and procollagen α(1)(II), procollagen α(2)(I) and hyaluronan synthase 2, quantitation of PGs, and agarose gel electrophoresis. Neocartilage produced at 20% O(2) appeared larger than that at 5% O(2). Histological staining showed that more PGs and type II collagen and better native cartilage structure were produced at 20% than at 5% O(2). The thickness of neocartilage increased during the culture period. Quantitative RT-PCR showed that the procollagen α(1)(II) mRNA expression level was significantly higher at 20% than at 5% O(2). However, no significant difference in gene expression and PG content was found between control and GS-treated cultures at either 20% or 5% O(2). Thus, in contrast to monolayer cultures, engineered cartilage from scaffold-free cultured chondrocytes at 20% O(2) produced better extracellular matrix (ECM) than that at 5% O(2). PGs were mainly large. Exogenous GS was not beneficial for the ECM in scaffold-free chondrocyte cultures.

  • 236.
    Qu, Chengjuan
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Myllymaa, Sami
    SIB-Labs, University of Eastern Finland, Kuopio, Finland; Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Prittinen, Juha
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Koistinen, Arto
    SIB-Labs, University of Eastern Finland, Kuopio, Finland.
    Lappalainen, Reijo
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Osteoblast behavior on various ultra short pulsed laser deposited surface coatings2013In: Materials Science and Engineering: C. Materials for Biological Applications, ISSN 0928-4931, Vol. 33, no 3, p. 1676-1682Article in journal (Refereed)
    Abstract [en]

    Ultra short pulsed laser deposition technique was utilized to create amorphous diamond, alumina and carbon nitride, and two different titania coatings on silicon wafers, thus producing five different surface deposited films with variable physico-chemical properties. The surface characterizations, including the roughness, the contact angle and the zeta potential measurements were performed before we tested the growth properties of human osteoblast-like Saos-2 cells on these surfaces (three separate experiments). The average roughness and hydrophobicity were the highest on titania-deposited surfaces, while carbon nitride was the most hydrophilic one. Osteoblasts on all surfaces showed a flattened, spread-out morphology, although on amorphous diamond the cell shape appeared more elongated than on the other surfaces. On rough titania, the area covered by the osteoblasts was smaller than on the other ones. Cell proliferation assay did not show any statistically significant differences.

  • 237.
    Qu, Chengjuan
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland;Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Puttonen, Katja
    Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Lindeberg, Heli
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Ruponen, Marika
    Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Hovatta, Outi
    Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
    Koistinaho, Jari
    Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Department of Oncology, Kuopio University Hospital, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Chondrogenic differentiation of human pluripotent stem cells in chondrocyte co-culture2013In: International Journal of Biochemistry and Cell Biology, ISSN 1357-2725, E-ISSN 1878-5875, Vol. 45, no 8, p. 1802-1812Article in journal (Refereed)
    Abstract [en]

    Chondrogenic differentiation of human embryonic (hESCs) or induced pluripotent stem cells (hiPSCs) has been achieved in embryoid bodies (EBs) by adding selected growth factors to the medium. Also chondrocyte-secreted factors have been considered to promote the chondrogenic differentiation. Hence, we studied whether co-culture with primary chondrocytes can induce hESCs or hiPSCs to differentiate into chondrocyte lineage. Co-culture of hESCs or hiPSCs was established in a transwell insert system in feeder-free culture conditions, while hESCs or hiPSCs grown alone in the wells were used as controls. After 3-week co-culture with weekly replenished chondrocytes, the chondrogenically committed cells (hCCCs) were evaluated by morphology, immunocytochemistry, quantitative real-time RT-PCR, and analysis of chondrogenic, osteogenic and adipogenic differentiation markers. The expressions of chondrocyte- and pluripotency-associated genes were frequently measured during the monolayer expansion of hCCCs from passage 1 to 10. Human CCCs displayed morphology similar to chondrocytes, and expressed chondrocyte-associated genes, which were declined following passaging, similarly to passaged chondrocytes. They also formed a chondrogenic cell pellet, and differentiated into chondrocytic cells, which secreted abundant extracellular matrix. Human CCCs also proliferated rapidly. However, they did not show osteogenic or adipogenic differentiation capacity. Our results show that co-culture of hESCs or hiPSCs with primary chondrocytes could induce specific chondrogenic differentiation.

  • 238.
    Qu, Cheng-Juan
    et al.
    Department of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland; Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Pöytäkangas, Teemu
    Department of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland.
    Jauhiainen, Marjo
    Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.
    Auriola, Seppo
    Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension.2009In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 337, no 1, p. 103-111, article id 19440735Article in journal (Refereed)
    Abstract [en]

    Low oxygen tension may change the dependence of chondrocytes on exogenous carbohydrate sources. In this study, we have investigated whether glucosamine sulphate (GS) stimulates proteoglycan synthesis, the mRNA expression of aggrecan and of type II collagen, and UDP-sugar levels in bovine primary chondrocytes under a low oxygen (O(2)) atmosphere. Chondrocytes from bovine femoral condyles were cultivated with or without GS or sulphate at various concentrations in low- (5.5 mM) or high-glucose (25 mM) DMEM under either a 5% or 20% O(2) atmosphere for 2 or 8 days after isolation. The mRNA expression of aggrecan and type II collagen and the synthesis of glycosaminoglycan (GAG) were determined by quantitative real-time reverse transcription with polymerase chain reaction and a [(35)S]-sulphate incorporation assay, respectively. Aggrecan promoter activity was analysed by a dual-luciferase reporter gene assay. Intracellular UDP-N-acetylhexosamines (UDP-HexN), UDP-glucuronic acid and UDP-hexoses were analysed by reversed-phase high-performance liquid chromatography electrospray ionization mass spectrometry. A low (5%) O(2) atmosphere significantly increased GAG synthesis, mRNA expression of aggrecan and of type II collagen and aggrecan promoter activity in bovine primary chondrocytes. A high (1 mM) concentration of GS was required to increase the level of UDP-HexN. However, GS did not increase GAG synthesis, aggrecan promoter activity or mRNA expression of aggrecan and of type II collagen. Interestingly, a 5% O(2) atmosphere increased the level of UDP-HexN in 8-day cultures without GS treatment. Thus, exogenous GS does not change chondrocyte metabolism, whereas a 5% O(2) atmosphere stimulates extracellular matrix production in bovine primary chondrocytes. The balance of UDP-sugars is changed under a 5% O(2) atmosphere for longer culture periods.

  • 239.
    Qu, Cheng-Juan
    et al.
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Rieppo, Jarno
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Hyttinen, Mika
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Kurkijärvi, Jatta
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
    Töyräs, Juha
    Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Human articular cartilage proteoglycans are not undersulfated in osteoarthritis.2007In: Connective Tissue Research, ISSN 0300-8207, E-ISSN 1607-8438, Vol. 48, no 1, p. 27-33Article in journal (Refereed)
    Abstract [en]

    Chondroitin sulfate is the major constituent of cartilage. Inadequate sulfate availability results in the production of undersulfated proteoglycans. In osteoarthritis, there is a net loss of articular cartilage proteoglycans. Theoretically, it is possible that during the progress of disease undersulfated glycosaminoglycans are synthesized producing proteoglycans with poorer biological properties. In this study, we tested whether in early human osteoarthritic articular cartilage (Mankin's score of 2 and 3) or more advanced disease (Mankin's score over 3), there are proteoglycans that contain a higher relative amount of nonsulfated chondroitin disaccharide isomer in their chondroitin sulfate chains by analyzing the molar ratios of chondroitin sulfate disaccharide isoforms with fluorophore-assisted carbohydrate electrophoresis. Our results indicated that the nonsulfated disaccharide of chondroitin sulfate formed in average only 1-2% of the total chondroitin sulfate. More important, the molar ratio of nonsulfated disaccharide did not appear to be increased in the osteoarthritic articular cartilage. We conclude that undersulfation of articular cartilage proteoglycans is not present in the human osteoarthritic joint.

  • 240.
    Riekkinen, Ossi
    et al.
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Hakulinen, Mikko
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Physics, University of Kuopio, Kuopio, Finland.
    Kallioniemi, Anssi
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Clinical Neurophysiology, Kuopio University Hospital and University of Kuopio, Kuopio, Finland.
    Acoustic properties of trabecular bone–relationships to tissue composition.2007In: Ultrasound in Medicine and Biology, ISSN 0301-5629, E-ISSN 1879-291X, Vol. 33, no 9, p. 1438-1444, article id 17561333Article in journal (Refereed)
    Abstract [en]

    In osteoporosis, changes in tissue composition and structure reduce bone strength and expose it to fractures. The current primary diagnostic technique, i.e., dual energy X-ray absorptiometry, measures areal bone mineral density (BMD) but provides no direct information on trabecular structure or organic composition. Although still poorly characterized, ultrasound techniques may bring about information on bone composition and structure. In this study, relationships of 2.25-MHz ultrasound speed, attenuation, reflection and backscattering with composition of human trabecular bone (n=26) were characterized experimentally, as well as by using numerical analyses. We also determined composition of the trabecular sample (fat and water content, bone volume fraction) and that of the calcified matrix (mineral, proteoglycan and collagen content of trabeculae). In experimental analyses, bone volume fraction and mineral content of the calcified matrix were the only determinants of BMD. Further, bone volume fraction served as the strongest determinant of ultrasound parameters (r=0.51-0.87). In numerical simulations, density and mechanical properties of the calcified matrix systematically affected ultrasound speed, attenuation, reflection and backscattering. However, partial correlation coefficients revealed only low associations(|r|<or=0.4) between the composition of calcified matrix and ultrasound parameters in experimental measurements. To conclude, the content and structure of calcified matrix, rather than its composition, affect more significantly acoustic properties of healthy trabecular bone.

  • 241.
    Rieppo, Lassi
    et al.
    University of Oulu, Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, Oulu, Finland; University of Eastern Finland, Department of Applied Physics, Kuopio, Finland.
    Kokkonen, Harri T.
    South Karelia Central Hospital, Department of Radiology, Lappeenranta, Finland.
    Kulmala, Katariina A. M.
    University of Eastern Finland, Department of Applied Physics, Kuopio, Finland.
    Kovanen, Vuokko
    University of Jyväskylä, Department of Health Sciences, Jyväskylä, Finland.
    Lammi, Mikko J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Health Science Center of Xi’an Jiaotong University, School of Public Health, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Töyräs, Juha
    University of Eastern Finland, Department of Applied Physics, Kuopio, Finland; Kuopio University Hospital, Diagnostic Imaging Center, Kuopio, Finland.
    Saarakkala, Simo
    University of Oulu, Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, Oulu, Finland; Oulu University Hospital, Department of Diagnostic Radiology, Oulu, Finland; University of Oulu and Oulu University Hospital, Medical Research Center Oulu, Oulu, Finland.
    Infrared microspectroscopic determination of collagen cross-links in articular cartilage2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 3, article id 035007Article in journal (Refereed)
    Abstract [en]

    Collagen forms an organized network in articular cartilage to give tensile stiffness to the tissue. Due to its long half-life, collagen is susceptible to cross-links caused by advanced glycation end-products. The current standard method for determination of cross-link concentrations in tissues is the destructive high-performance liquid chromatography (HPLC). The aim of this study was to analyze the cross-link concentrations nondestructively from standard unstained histological articular cartilage sections by using Fourier transform infrared (FTIR) microspectroscopy. Half of the bovine articular cartilage samples (n=27) were treated with threose to increase the collagen cross-linking while the other half (n=27) served as a control group. Partial least squares (PLS) regression with variable selection algorithms was used to predict the cross-link concentrations from the measured average FTIR spectra of the samples, and HPLC was used as the reference method for cross-link concentrations. The correlation coefficients between the PLS regression models and the biochemical reference values were r=0.84 (p<0.001), r=0.87 (p<0.001) and r=0.92 (p<0.001) for hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP), and pentosidine (Pent) cross-links, respectively. The study demonstrated that FTIR microspectroscopy is a feasible method for investigating cross-link concentrations in articular cartilage.

  • 242.
    Rieppo, Lassi
    et al.
    Department of Physics, University of Kuopio, Kuopio, Finland; BioMater Centre, University of Kuopio, Kuopio, Finland.
    Saarakkala, Simo
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Närhi, Tommi
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Holopainen, Jaakko
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland; BioMater Centre, University of Kuopio, Kuopio, Finland.
    Rieppo, Jarno
    BioMater Centre, University of Kuopio, Kuopio, Finland; Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Quantitative analysis of spatial proteoglycan content in articular cartilage with Fourier transform infrared imaging spectroscopy: Critical evaluation of analysis methods and specificity of the parameters.2010In: Microscopy research and technique (Print), ISSN 1059-910X, E-ISSN 1097-0029, Vol. 73, no 5, p. 503-512, article id 19839035Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the specificity of the current Fourier transform infrared imaging spectroscopy (FT-IRIS) methods for the determination of depthwise proteoglycan (PG) content in articular cartilage (AC). In addition, curve fitting was applied to study whether the specificity of FT-IRIS parameters for PG determination could be improved.

    METHODS: Two sample groups from the steer AC were prepared for the study (n = 8 samples/group). In the first group, chondroitinase ABC enzyme was used to degrade the PGs from the superficial cartilage, while the samples in the second group served as the controls. Samples were examined with FT-IRIS and analyzed using previously reported direct absorption spectrum techniques and multivariate methods and, in comparison, by curve fitting. Safranin O-stained sections were measured with digital densitometry to obtain a reference for depthwise PG distribution.

    RESULTS: Carbohydrate region-based absorption spectrum methods showed a statistically weaker correlation with the PG reference distributions than the results of the curve fitting (subpeak located approximately at 1,060 cm(-1)). Furthermore, the shape of the depthwise profiles obtained using the curve fitting was more similar to the reference profiles than with the direct absorption spectrum analysis.

    CONCLUSIONS: Results suggest that the current FT-IRIS methods for PG analysis lack the specificity for quantitative measurement of PGs in AC. The curve fitting approach demonstrated that it is possible to improve the specificity of the PG analysis. However, the findings of the present study suggest that further development of the FT-IRIS analysis techniques is still needed.

  • 243. Roos, Ewa M.
    et al.
    Irrgang, James J.
    Lysholm, Jack
    North Sweden Univ Hosp, Dept Orthopaed, Umeå, Sweden.
    Comments on: Validation Study of an Electronic Method of Condensed Outcomes Tools Reporting in Orthopaedics2014In: Journal of knee surgery, ISSN 1538-8506, Vol. 27, no 2, p. 165-166Article in journal (Refereed)
  • 244. Rydholm, Anders
    et al.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Happy birthday, Acta!2010In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, no 1, p. 1-2Article in journal (Other (popular science, discussion, etc.))
  • 245.
    Röhrl, Stephan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Li, Ming G
    Perth Orthopaedic Institute, University of Western Australia.
    Pedersen, E
    Department of Orthopaedic Surgery, Sundsvall Hospital.
    Ullmark, G
    Department of Orthopaedic Surgery, Gävle Hospital.
    Nivbrant, B
    Perth Orthopaedic Institute, University of Western Australia.
    Migration pattern of a short femoral neck preserving stem2006In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 448, no July, p. 73-78Article in journal (Refereed)
    Abstract [en]

    AB The CFP stem represents a short collared neck-retaining stem with very proximal metaphyseal anchoring along the calcar combined with up-to-date metallurgy. Despite theoretical advantages, the stability and clinical outcome are unknown. We prospectively measured the migration pattern of this new stem and cup. Twenty-six patients (26 hips) with a mean age of 54 years (range, 40-66 years) underwent THA and were followed for 2 years with radiostereometry, radiographs, and clinical scores. The stem showed some early retroversion (mean, SEM 0.6[degrees], 0.3), but stabilized before 1 year. Subsidence (0.05 mm, 0.06) and varus-valgus tilting (0.03[degrees], 0.01) were low. We observed no bone loss in the calcar region. Factors related to patients, implant design, and implantation did not predict migration patterns. The two-dimensional wear of the ceramic/conventional articulation was 0.09 mm at 2-24 months. The low migration of this short neck preserving stem suggests a favorable long-term outcome but longer followup is needed to substantiate this prediction. This design might become an alternative to standard stems and hip resurfacing. Level of Evidence: Therapeutic Level IV. See The Guidelines for Authors for a complete description of levels of evidence.

  • 246.
    Röhrl, Stephan M
    et al.
    Department of Orthopaedics, Oslo University Hospital, Oslo.
    Nivbrant, Bo
    Perth Orthopaedic Institute, University of Western Australia, Perth, Australia.
    Nilsson, Kjell G
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    No adverse effects of submelt-annealed highly crosslinked polyethylene in cemented cups: an RSA study of 8 patients 10 years after surgery2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 2, p. 148-152Article in journal (Refereed)
    Abstract [en]

    Background and purpose Highly crosslinked polyethylene (PE) is in standard use worldwide. Differences in the crosslinking procedure may affect the clinical performance. Experimenatal data from retrieved cups have shown free radicals and excessive wear of annealed highly crosslinked PE. We have previously reported low wear and good clinical performance after 6 years with this implant, and now report on the 10-year results. Patients and methods In 8 patients, we measured wear of annealed highly crosslinked PE prospectively with radiostereometry after 10 years. Activity was assessed by UCLA activity score and a specifically designed activity score. Conventional radiographs were evaluated for osteolysis and clinical outcome by the Harris hip score (HHS). Results The mean (95% CI) proximal head penetration for highly crosslinked PE after 10 years was 0.07 (-0.015 to 0.153) mm, and the 3D wear was 0.2 (0.026 to 0.36) mm. Without creep, proximal head penetration was 0.02 (-0.026 to 0.066) mm and for 3D penetration was 0.016 (-0.47 to 0.08) mm. This represents an annual proximal wear of less than 2 mu m. All cups were clinically and radiographically stable but showed a tendency of increased rotation after 5 years. Interpretation Wear for annealed highly crosslinked PE is extremely low up to 10 years. Free radicals do not affect mechanical performance or lead to clinically adverse effects. Creep stops after the first 6 months after implantation. Highly crosslinked PE is a true competitor of hard-on-hard bearings.

  • 247.
    Saarakkala, Simo
    et al.
    Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Laasanen, Mikko
    Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Törrönen, Kari
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lappalainen, Reijo
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Ultrasound indentation of normal and spontaneously degenerated bovine articular cartilage.2003In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 11, no 9, p. 697-705, article id 12954241Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We have previously developed a handheld ultrasound indentation instrument for the diagnosis of cartilage degeneration. The instrument has been demonstrated to be capable of quantifying mechanical and acoustic properties of enzymatically degraded and normal bovine articular cartilage in vitro and in situ. The aim of this study was to investigate the sensitivity of the instrument to distinguish between normal and spontaneously degenerated (e.g., in osteoarthrosis) articular cartilage in vitro.

    DESIGN: Thirty articular cartilage samples were prepared from the bovine lateral patellae: 19 patellae with different degenerative stages and 11 patellae with visually normal appearance. Cartilage thickness, stiffness (dynamic modulus) and ultrasound reflection from the cartilage surface were measured with the handheld instrument. Subsequently, biomechanical, histological and biochemical reference measurements were conducted.

    RESULTS: Reproducibility of the measurements with the ultrasound indentation instrument was good. Standardized coefficient of variation was < or =6.1% for thickness, dynamic modulus and reflection coefficient. Linear correlation between the dynamic modulus, measured with the ultrasound indentation instrument, and the reference dynamic modulus was high (r=0.993, n=30, P<0.05). Ultrasound reflection coefficient, as determined from the cartilage surface, showed high linear correlations (typically r(2)>0.64, n=30, P<0.05) with the cartilage composition and histological or mechanical properties. The instrument was superior compared to visual evaluation in detecting tissue degeneration.

    CONCLUSION: This study indicates that the ultrasound indentation technique and instrument may significantly improve the early diagnosis of cartilage degeneration. The results revealed that visual evaluation is insensitive for estimating the structural and mechanical properties of articular cartilage at the initial stages of degeneration.

  • 248. Sagafors, Dagrun
    et al.
    Kleggetveit, Inge P.
    Helås, Tormod
    Schmidt, Roland
    Minde, Jan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Namer, Barbara
    Schmelz, Martin
    Jorum, Ellen
    Single-Fiber Recordings Of Nociceptive Fibers in Patients With HSAN Type V With Congenital Insensitivity To Pain2016In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 32, no 7, p. 636-642Article in journal (Refereed)
    Abstract [en]

    Objectives: Nerve growth factor (NGF) is a protein important for growth and survival, but also for modulation of sensitivity of nociceptors and sympathetic neurons. The purpose of the present study was to investigate the effects of reduced NGF signaling in patients with hereditary sensory and autonomic neuropathies type V, congenital insensitivity to pain, caused by a mutation of the NGF beta gene, including a characterization of single nociceptive fibers using microneurography (MNG).

    Materials and Methods: One homozygote and 2 heterozygote patients with this mutation were examined with electromyography/neurography, thermal testing, quantitative sudomotor axon reflex test, and electrically induced axon reflex erythema in addition to MNG.

    Results: Low quantitative sudomotor axon reflex test measurements of 0.02 (left foot) and 0.03 (right foot) mL/cm(2) and elevated thermal thresholds for warmth and cold detection testing showed clear impairment of small nerve fibers, both sudomotor efferent and somatic afferent fibers, in the patient homozygote for the mutation. MNG from one of the heterozygote patients revealed changes in the small nociceptive fibers in skin, including abnormally low conduction velocity, spontaneous activity in A-delta fibers and C-nociceptors and abnormal or lacking response to heat.

    Discussion: The findings of grossly intact pain thresholds compared with anamnestic insensitivity of pain in deep somatic tissue such as bone suggest a gradient of impairment dependent on different NGF availability in various tissues. Even though these patients in some aspects report insensitivity to pain, they also report chronic spontaneous pain as their main symptom, strikingly highlighting differential mechanisms of insensitivity to evoked pain versus spontaneous pain.

  • 249.
    Sahlman, Janne
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Inkinen, Ritva
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Hirvonen, Teemu
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Pirkko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Nieminen, Jyrki
    Department of Surgery, Tampere University Hospital, Tampere, Finland.
    Lapveteläinen, Tuomo
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Prockop, Darwin
    Center for Gene Therapy, School of Medicine, MCP Hahnemann University, Philadelphia, Pennsylvania, USA.
    Arita, Machiko
    Center for Gene Therapy, School of Medicine, MCP Hahnemann University, Philadelphia, Pennsylvania, USA.
    Li, Shi-Wu
    Center for Gene Therapy, School of Medicine, MCP Hahnemann University, Philadelphia, Pennsylvania, USA.
    Hyttinen, Mika
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Puustjärvi, Kaija
    Department of Physical Medicine and Rehabilitation, Kuopio University Hospital, Kuopio, Finland.
    Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen.2001In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 26, no 23, p. 2558-2565, article id 11725236Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN: Skeletal tissues of mice with an inactivated allele of the Col2a1 gene for Type II collagen ("heterozygous knockout") were studied.

    OBJECTIVE: To determine whether a heterozygous inactivation of the Col2a1 gene has a role in the etiology of spine disorders such as disc degeneration.

    SUMMARY OF BACKGROUND DATA: Mutations in the COL2A1, COL11A1, COL11A2, and COL9A2 genes have been linked to spine disorders. However, the mechanism by which genetic factors lead to disc degeneration still are largely unknown.

    METHODS: Spine tissues were studied using radiograph analyses; conventional, quantitative, and polarized light microscopy; immunohistochemistry for the major extracellular components, and in situ hybridization for procollagens alpha1(I) and alpha1(II). Voluntary running activity also was monitored in half of the mice.

    RESULTS: As the findings showed, 1-month-old heterozygous knockout mice had shorter limb bones, skulls, and spines, as well as thicker and more irregular vertebral endplates, which calcified earlier than in the control mice. They also had a lower concentration of glycosaminoglycans in the anulus fibrosus, in the endplates, and in the vertebral bone than the controls. These features in the heterozygous knockout mice were compensated by the age of 15 months. However, the long bones and skulls of the mature heterozygous mice remained shorter than those of the controls. Gene-deficient mice used the running wheel less. However, physical exercise did not induce any marked structural changes in the skeleton.

    CONCLUSION: Mice with heterozygous knockout of Col2a1 show subtle early skeletal manifestations that bear some resemblance to those of human spine disorders.

  • 250.
    Sahlman, Janne
    et al.
    Seinäjoki Central Hospital, Seinäjoki, Finland.
    Pitkänen, Marja
    University Hospital of Kuopio, Kuopio, Finland.
    Prockop, Darwin
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Arita, Machiko
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Li, Shi-Wu
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Långsjö, Teemu
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Puustjärvi, Kaija
    Helsinki University Hospital, Helsinki, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    A human COL2A1 gene with an Arg519Cys mutation causes osteochondrodysplasia in transgenic mice.2004In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 50, no 10, p. 3153-3160, article id 15476249Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: An arginine-to-cysteine substitution at position 519 of the COL2A1 gene causes early generalized osteoarthritis with mild chondrodysplasia in humans. In this study, a human COL2A1 gene with the same mutation was introduced into a murine genome having 1 or no alleles of the murine Col2a1 gene, and the skeletal phenotypes of the transgenic mice were compared with those of control mice.

    METHODS: Mice with 1 allele of the normal murine Col2a1 gene and 1 allele of the mutated human COL2A1 gene (n = 10), those with no murine Col2a1 gene and 2 alleles of the mutated human COL2A1 gene (n = 13), those with no murine Col2a1 gene and only 1 allele of the mutated COL2A1 gene (n = 9), and normal control mice (n = 11) were studied for skeletal abnormalities, using radiographic imaging and light microscopic analyses of histologic sections. The collagen network of cartilage was also investigated with transmission electron microscopy.

    RESULTS: At 2 months of age, all transgenic mice had dysplastic changes in their long bones, flattened vertebral bodies, and osteoarthritic changes in their joints. The intervertebral discs of the transgenic animals were degenerated, and their histologic structure was disturbed. The changes were more severe in mice with no murine Col2a1 allele.

    CONCLUSION: The human COL2A1 gene with the Arg519Cys mutation causes osteochondrodysplasia in mice, as it does in humans.

234567 201 - 250 of 316
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