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Unexpected presence of the neurotrophins NGF and BDNF and the neurotrophin receptor p75 in the tendon cells of the human Achilles tendon
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
2009 (English)In: Histology and Histopathology, ISSN 0213-3911, Vol. 24, no 7, 839-848 p.Article in journal (Refereed) Published
Abstract [en]

Neurotrophins are substances that have been shown to be important in growth and remodelling phases in different types of tissue. There is no information concerning the possible occurrences of neurotrophins and their receptors in tendons. In this study, sections of both chronic painful (tendinosis) and pain-free (non-tendinosis) human Achilles tendons were immunohistochemically stained with antibodies against the neurotrophins NGF and BDNF, and their receptors TrkA, TrkB and p75. There were marked immunoreactions for NGF and BDNF in the tendon cells (tenocytes) of both tendinosis and non-tendinosis specimens. The tenocytes were also reactive for the receptor p75, but not for the receptors TrkA and TrkB. In addition, p75 immunoreactions were seen in nerve fascicles and in the walls of arterioles. This is the first study to identify neurotrophins in the tenocytes of human tendon. It is clear from this study that the local cells of tendons are sources of neurotrophins. The neurotrophins may play an important role in the tendon through their interaction with the receptor p75 in the tenocytes. These interactions may regulate tropic modulatory, and apoptotic effects. In conclusion, the observations show a new concept concerning production and function of neurotrophins, namely in the tenocytes of tendons.

Place, publisher, year, edition, pages
2009. Vol. 24, no 7, 839-848 p.
Keyword [en]
Achilles tendon, Neurotrophins, Tendinopathy, p75, NGF
National Category
Sport and Fitness Sciences Physiology
URN: urn:nbn:se:umu:diva-24109PubMedID: 19475530OAI: diva2:226089
Available from: 2009-06-30 Created: 2009-06-30 Last updated: 2013-01-04Bibliographically approved
In thesis
1. TNF-α and neurotrophins in Achilles tendinosis
Open this publication in new window or tab >>TNF-α and neurotrophins in Achilles tendinosis
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Tenocytes are the principal cells of the human Achilles tendon. In tendinosis, changes in the metabolism and morphology of these cells occur. Neurotrophins are growth factors essential for the development of the nervous system. Tumour necrosis factor alpha (TNF-α) has been found to kill sarcomas but has destructive effects in several major diseases. The two systems have interaction effects and are associated with apoptosis, proliferation, and pain signalling in various diseases. Whether these systems are present in the Achilles tendon and in Achilles tendinosis is unknown. The hypothesis is that the tenocytes produce substances belonging to these systems. In Studies I–III, we show that the potent effects of these substances are also likely to occur in the Achilles tendon. We found tenocyte immunoreactions for the neurotrophins brain-derived neurotrophic factor (BDNF), the nerve growth factor (NGF), the neurotrophin receptor p75, and for TNF-α and both of its receptors, TNFR1 and TNFR2. This occurred in both subjects with painful mid-portion Achilles tendinosis, and in controls. Furthermore, we found mRNA expression for BDNF and TNF-α in tenocytes, which proves that these cells produce these substances. TNFR1 mRNA was also detected for the tenocytes, and TNFR1 immunoreactions were upregulated in tendinosis tendons. This might explain why tenocytes in tendinosis undergo apoptosis more often than in normal tendons. Total physical activity (TPA) level and blood concentration of both soluble TNFR1 and BDNF were measured in Study IV. The results showed that the blood concentration of both factors were similar in subjects with tendinosis and in controls. Nevertheless, the TPA level was related to the blood concentration of sTNFR1 in tendinosis, but not in controls. This relationship should be studied further. The findings of this doctoral thesis show that neurotrophin and TNF-α systems are expressed in the Achilles tendon. We believe that the functions include tissue remodelling, proliferation and apoptosis.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2013. 121 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1538
Achilles tendon, tendinosis, tendinopathy, neurotrophins, TNF-alpha, physical acitivity, apoptosis, proliferation, pain, remodelling
National Category
Basic Medicine
Research subject
Human Anatomy
urn:nbn:se:umu:diva-63660 (URN)978-91-7459-525-3 (ISBN)
Public defence
2013-01-25, Biologihuset, sal BiA201, Umeå universitet, Umeå, 09:00 (Swedish)
Available from: 2013-01-04 Created: 2013-01-03 Last updated: 2014-12-18Bibliographically approved

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