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Andersson, Gustav
Publications (10 of 21) Show all publications
Andersson, G., Orädd, G., Sultan, F. & Novikov, L. N. (2018). In vivo Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Tractography of a Sciatic Nerve Injury Model in Rat at 9.4T. Scientific Reports, 8, Article ID 12911.
Open this publication in new window or tab >>In vivo Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Tractography of a Sciatic Nerve Injury Model in Rat at 9.4T
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12911Article in journal (Refereed) Published
Abstract [en]

Peripheral nerve injuries result in severe loss of sensory and motor functions in the afflicted limb. There is a lack of standardised models to non-invasively study degeneration, regeneration, and normalisation of neuronal microstructure in peripheral nerves. This study aimed to develop a non-invasive evaluation of peripheral nerve injuries, using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and tractography on a rat model of sciatic nerve injury. 10 female Sprague Dawley rats were exposed to sciatic nerve neurotmesis and studied using a 9.4 T magnet, by performing DTI and DKI of the sciatic nerve before and 4 weeks after injury. The distal nerve stump showed a decrease in fractional anisotropy (FA), mean kurtosis (MK), axonal water fraction (AWF), and radial and axonal kurtosis (RK, AK) after injury. The proximal stump showed a significant decrease in axial diffusivity (AD) and increase of MK and AK as compared with the uninjured nerve. Both mean diffusivity (MD) and radial diffusivity (RD) increased in the distal stump after injury. Tractography visualised the sciatic nerve and the site of injury, as well as local variations of the diffusion parameters following injury. In summary, the described method detects changes both proximal and distal to the nerve injury.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-151785 (URN)10.1038/s41598-018-30961-1 (DOI)000442870300089 ()30150697 (PubMedID)
Funder
Swedish Research Council, 2014-2306
Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2018-09-14Bibliographically approved
Andersson, G., Backman, L. J., Christensen, J. & Alfredson, H. (2017). Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon. Histology and Histopathology, 32(3), 263-270
Open this publication in new window or tab >>Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon
2017 (English)In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 32, no 3, p. 263-270Article in journal (Refereed) Published
Abstract [en]

Background/Aim. In a condition of pain in the Achilles tendon insertion there are multiple structures involved, such as the Achilles tendon itself, the retrocalcaneal bursa and a bony protrusion at the calcaneal tuberosity called Haglund's deformity. The innervation patterns of these structures are scarcely described, and the subcutaneous calcaneal bursa is traditionally not considered to be involved in the pathology. This study aimed at describing the innervation patterns of the four structures described above to provide a better understanding of possible origins of pain at the Achilles tendon insertion.

Methods. Biopsies were taken from 10 patients with insertional Achilles tendinopathy, which had pathological changes in the subcutaneous and retrocalcaneal bursae, a Haglund deformity and Achilles tendon tendinopathy as verified by ultrasound. The biopsies were stained using immunohistochemistry in order to delineate the innervation patterns in the structures involved in insertional Achilles tendinopathy.

Results. Immunohistochemical examinations found that the subcutaneous bursa scored the highest using a semi-quantitative evaluation of the degree of innervation when compared to the retrocalcaneal bursa, the Achilles tendon, and the calcaneal bone.

Conclusions. These findings suggest that the subcutaneous bursa, which is traditionally not included in surgical treatment, may be a clinically important factor in insertional Achilles tendinopathy.

Keywords
Insertional Achilles tendinopathy, Innervation, Subcutaneous bursa, Retrocalcaneal bursa
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-130214 (URN)10.14670/HH-11-790 (DOI)000390220000006 ()
Available from: 2017-02-02 Created: 2017-01-14 Last updated: 2019-02-22Bibliographically approved
Ward, E. R., Andersson, G., Backman, L. J. & Gaida, J. E. (2016). Fat pads adjacent to tendinopathy: more than a coincidence?. British Journal of Sports Medicine, 50(24), 1491-1492
Open this publication in new window or tab >>Fat pads adjacent to tendinopathy: more than a coincidence?
2016 (English)In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 50, no 24, p. 1491-1492Article in journal, Editorial material (Refereed) Published
National Category
Surgery Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-131097 (URN)10.1136/bjsports-2016-096174 (DOI)000391302100004 ()27553835 (PubMedID)
Available from: 2017-02-14 Created: 2017-02-14 Last updated: 2019-02-22Bibliographically approved
Spang, C., Alfredson, H., Docking, S. I., Masci, L. & Andersson, G. (2016). The plantaris tendon: a narrative review focusing on anatomical features and clinical importance. The Bone & Joint Journal, 98B(10), 1312-1319
Open this publication in new window or tab >>The plantaris tendon: a narrative review focusing on anatomical features and clinical importance
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2016 (English)In: The Bone & Joint Journal, ISSN 2049-4394, E-ISSN 2049-4408, Vol. 98B, no 10, p. 1312-1319Article, review/survey (Refereed) Published
Abstract [en]

In recent years, the plantaris tendon has been implicated in the development of chronic painful mid-portion Achilles tendinopathy. In some cases, a thickened plantaris tendon is closely associated with the Achilles tendon, and surgical excision of the plantaris tendon has been reported to be curative in patients who have not derived benefit following conservative treatment and surgical interventions. The aim of this review is to outline the basic aspects of, and the recent research findings, related to the plantaris tendon, covering anatomical and clinical studies including those dealing with histology, imaging and treatment.

National Category
Orthopaedics Surgery
Identifiers
urn:nbn:se:umu:diva-127607 (URN)10.1302/0301-620X.98B10.37939 (DOI)000385337900003 ()27694583 (PubMedID)
Available from: 2016-12-07 Created: 2016-11-16 Last updated: 2018-06-09Bibliographically approved
Forsgren, S., Alfredson, H. & Andersson, G. (2015). Further proof of the existence of a non-neuronal cholinergic system in the human Achilles tendon: Presence of the AChR alpha 7 receptor in tendon cells and cells in the peritendinous tissue. International Immunopharmacology, 29(1), 195-200
Open this publication in new window or tab >>Further proof of the existence of a non-neuronal cholinergic system in the human Achilles tendon: Presence of the AChR alpha 7 receptor in tendon cells and cells in the peritendinous tissue
2015 (English)In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 29, no 1, p. 195-200Article in journal (Refereed) Published
Abstract [en]

Human tendon cells have the capacity for acetylcholine (ACh) production. It is not known if the tendon cells also have the potential for ACh breakdown, nor if they show expression of the nicotinic acetylcholine receptor AChR alpha 7 (alpha 7nAChR). Therefore, tendon tissue specimens from patients with midportion Achilles tendinopathy/tendinosis and from normal midportion Achilles tendons were examined. Reaction for the degradative enzyme acetylcholinesterase (AChE) was found in some tenocytes in only a few tendinopathy tendons, and was never found in those of control tendons. Tenocytes displayed more regularly alpha 7nAChR immunoreactivity. However, there was a marked heterogeneity in the degree of this reaction within and between the specimens. alpha 7nAChR immunoreactivity was especially pronounced for tenocytes showing an oval/widened appearance. There was a tendency that the magnitude of alpha 7nAChR immunoreactivity was higher in tendinopathy tendons as compared to control tendons. A stronger alpha 7nAChR immunoreactivity than seen for tenocytes was observed for the cells in the peritendinous tissue. It is likely that the alpha 7nAChR may be an important part of an auto-and paracrine loop of non-neuronal ACh that is released from the tendon cells. The effects may be related to proliferative and blood vessel regulatory functions as well as features related to collagen deposition. ACh can furthermore be of importance in leading to anti-inflammatory effects in the peritendinous tissue, a tissue nowadays considered to be of great relevance for the tendinopathy process. Overall, the findings show that tendon tissue, a tissue known to be devoid of cholinergic innervation, is a tissue in which there is a marked non-neuronal cholinergic system.

Keywords
Cholinergic, Nicotinic, Achilles, Tendons, Tenocytes
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-113448 (URN)10.1016/j.intimp.2015.04.055 (DOI)000365365500033 ()25981114 (PubMedID)
Available from: 2015-12-18 Created: 2015-12-18 Last updated: 2018-06-07Bibliographically approved
Christensen, J., Alfredson, H. & Andersson, G. (2015). Protease-activated receptors in the Achilles tendon-a potential explanation for the excessive pain signalling in tendinopathy. Molecular Pain, 11, Article ID 13.
Open this publication in new window or tab >>Protease-activated receptors in the Achilles tendon-a potential explanation for the excessive pain signalling in tendinopathy
2015 (English)In: Molecular Pain, ISSN 1744-8069, E-ISSN 1744-8069, Vol. 11, article id 13Article in journal (Refereed) Published
Abstract [en]

Background/Aim: Tendinopathies are pathological conditions of tissue remodelling occurring in the major tendons of the body, accompanied by excessive nociceptive signalling. Tendinopathies have been shown to exhibit an increase in the number of mast cells, which are capable of releasing histamine, tryptase and other substances upon activation, which may play a role in the development of tendinopathies. This study set out to describe the distribution patterns of a family of receptors called protease-activated receptors (PARs) within the Achilles tendon. These four receptors (PAR1, PAR2, PAR3, PAR4) are activated by proteases, including tryptase released from mast cells, and are involved in fibrosis, hyperalgesia and neovascularisation, which are changes seen in tendinopathies. Method: In order to study which structures involved in tendinopathy that these proteases can affect, biopsies from patients suffering of mid-portion Achilles tendinosis and healthy controls were collected and examined using immunohistochemistry. Tendon cells were cultured to study in vitro expression patterns. Results: The findings showed a distribution of PARs inside the tendon tissue proper, and in the paratendinous tissue, with all four being expressed on nerves and vascular structures. Double staining showed co-localisation of PARs with nociceptive fibres expressing substance P. Concerning tenocytes, PAR2, PAR3, and PAR4, were found in both biopsies of tendon tissue and cultured tendon cells. Conclusions: This study describes the expression patterns of PARs in the mid-portion of the Achilles tendon, which can help explain the tissue changes and increased pain signalling seen in tendinopathies. These findings also show that in-vitro studies of the effects of these receptors are plausible and that PARs are a possible therapeutic target in the future treatment strategies of tendinopathy.

Keywords
Achilles tendon, Protease-activated receptor, Mast cell, Tendinopathy
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:umu:diva-102218 (URN)10.1186/s12990-015-0007-4 (DOI)000351261900001 ()
Available from: 2015-05-05 Created: 2015-04-22 Last updated: 2018-06-07Bibliographically approved
Huisman, E. S., Andersson, G., Scott, A., Reno, C. R., Hart, D. A. & Thornton, G. M. (2014). Regional molecular and cellular differences in the female rabbit Achilles tendon complex: potential implications for understanding responses to loading. Journal of Anatomy, 224(5), 538-547
Open this publication in new window or tab >>Regional molecular and cellular differences in the female rabbit Achilles tendon complex: potential implications for understanding responses to loading
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2014 (English)In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 224, no 5, p. 538-547Article in journal (Refereed) Published
Abstract [en]

The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real-time reverse transcription-quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase-2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon.

Keywords
mRNA expression, rabbit Achilles tendon complex, regional differences
National Category
Medical and Health Sciences
Research subject
Human Anatomy; morfologisk zoologi med utvecklingsbiologisk inriktning
Identifiers
urn:nbn:se:umu:diva-88381 (URN)10.1111/joa.12169 (DOI)000333578700002 ()
Available from: 2014-05-20 Created: 2014-05-05 Last updated: 2018-06-07Bibliographically approved
Backman, L. J., Andersson, G., Fong, G., Alfredson, H., Scott, A. & Danielson, P. (2013). Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: comparison between two model systems. Scandinavian Journal of Medicine and Science in Sports, 23(6), 687-696
Open this publication in new window or tab >>Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: comparison between two model systems
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2013 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 23, no 6, p. 687-696Article in journal (Refereed) Published
Abstract [en]

The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α(2A) AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α(2A) AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α(2A) AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
Keywords
tendinopathy, exercise, cytokines, neurotrophins, alpha(2A) adrenoreceptor, Tendinosis, Achilles tendon
National Category
Sport and Fitness Sciences Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-53462 (URN)10.1111/j.1600-0838.2011.01442.x (DOI)000330192000007 ()22292987 (PubMedID)
Funder
Swedish Research Council, 521-2009-2921Swedish National Centre for Research in Sports, 54/10, P2011-0170
Available from: 2012-03-27 Created: 2012-03-27 Last updated: 2019-02-22Bibliographically approved
Fong, G., Backman, L., Andersson, G., Scott, A. & Danielson, P. (2013). Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway. Cell and Tissue Research, 351(3), 465-475
Open this publication in new window or tab >>Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway
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2013 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 351, no 3, p. 465-475Article in journal (Refereed) Published
Abstract [en]

Studies of human patellar and Achilles tendons have shown that primary tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic tendon pain) with tendinosis, the tendon tissue is characterised by hypercellularity and angiogenesis, both of which might be influenced by ACh. In this study, we have tested the hypothesis that ACh increases the proliferation rate of tenocytes through mAChR stimulation and have examined whether this mechanism operates via the extracellular activation of the epidermal growth factor receptor (EGFR), as shown in other fibroblastic cells. By use of primary human tendon cell cultures, we identified cells expressing vimentin, tenomodulin and scleraxis and found that these cells also contained enzymes related to ACh synthesis and release (choline acetyltransferase and vesicular acetylcholine transporter). The cells furthermore expressed mAChRs of several subtypes. Exogenously administered ACh stimulated proliferation and increased the viability of tenocytes in vitro. When the cells were exposed to atropine (an mAChR antagonist) or the EGFR inhibitor AG1478, the proliferative effect of ACh decreased. Western blot revealed increased phosphorylation, after ACh stimulation, for both EGFR and the extracellular-signal-regulated kinases 1 and 2. Given that tenocytes have been shown to produce ACh and express mAChRs, this study provides evidence of a possible autocrine loop that might contribute to the hypercellularity seen in tendinosis tendon tissue.

Place, publisher, year, edition, pages
Springer-Verlag New York, 2013
Keywords
Muscarinic acetylcholine receptors, Tendinopathy, Tendinosis, Choline acetyltransferase, Vesicular acetylcholine transporter, Atropine, Non-neuronal acetylcholine, Human
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-67794 (URN)10.1007/s00441-012-1530-5 (DOI)000315490400011 ()
Available from: 2013-04-05 Created: 2013-04-03 Last updated: 2019-02-22Bibliographically approved
Backman, L., Andersson, G., Wennstig, G., Forsgren, S. & Danielson, P. (2011). Endogenous substance P production in the Achilles tendon increases with loading in an in vivo model of tendinopathy: peptidergic elevation preceding tendinosis-like tissue changes. Journal of Musculoskeletal and Neuronal Interactions - JMNI, 11(2), 133-140
Open this publication in new window or tab >>Endogenous substance P production in the Achilles tendon increases with loading in an in vivo model of tendinopathy: peptidergic elevation preceding tendinosis-like tissue changes
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2011 (English)In: Journal of Musculoskeletal and Neuronal Interactions - JMNI, ISSN 1108-7161, Vol. 11, no 2, p. 133-140Article in journal (Refereed) Published
Abstract [en]

Objectives: To quantify the intratendinous levels of substance P (SP) at different stages of overload in an established modelfor Achilles tendinopathy (rabbit). Also, to study the distribution of the SP-receptor, the NK-1R, and the source of SP, in thetendon. 

Methods: Animals were subjected to the overuse protocol for 1, 3 or 6 weeks. One additional group served as unexercisedcontrols. Immunoassay (EIA), immunohistochemistry (IHC), and in situ hybridisation (ISH) were performed.

Results: EIA revealedincreased SP-levels in the Achilles tendon of the exercised limb in all the experimental groups as compared to in thecontrols (statistically significant; p=0.01). A similar trend in the unexercised Achilles tendon was observed but was not statisticallysignificant (p=0.14). IHC and in ISH illustrated reactions of both SP and NK-1R mainly in blood vessel walls, but the receptorwas also found on tenocytes.

Conclusions: Achilles tendon SP-levels are elevated already after 1 week of loading. This showsthat increased SP-production precedes tendinosis, as tendinosis-like changes occur only after a minimum of 3 weeks of exercise,as shown in a recent study using this model. We propose that central neuronal mechanism may be involved as similar trends wereobserved in the contralateral Achilles tendon.

Place, publisher, year, edition, pages
International Society of Musculoskeletal and Neuronal Interactions, 2011
Keywords
Neuropeptides, Neurokinin-1 Receptor, Animal Model, Overuse Injuries, Rabbit
National Category
Sport and Fitness Sciences Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-42299 (URN)000291698500007 ()21625050 (PubMedID)
Available from: 2011-04-07 Created: 2011-04-07 Last updated: 2019-02-22Bibliographically approved
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