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Myostatin in tendon maintenance and repair
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
Max Planck Institute.
Max Planck Institute.
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2009 (English)In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 27, no 4, 247-254 p.Article in journal (Refereed) Published
Abstract [en]

Myostatin, a negative regulator of muscle growth, has recently been found to be expressed in tendons. Myostatin-deficient mice have weak and brittle tendons, which suggest that myostatin could be important for tendon maintenance. Follistatin expression in the callus tissue after tendon transection is influenced by loading. We found that follistatin antagonises myostatin, but not GDF-5 or OP-1 in vitro. To study if myostatin might play a physiological role in soft tissue, we transected 64 rat Achilles tendons and studied the gene expression for myostatin and its receptors at four different time-points during healing. Intact tendons were also studied. All samples were studied with or without mechanical loading. Unloading was achieved with botulinum toxin injections in the calf muscles. The expression of the myostatin gene was more than 40 times higher in intact tendons than in the callus tissue during tendon healing. The expression of myostatin was also influenced by loading status in both intact and healing tendons. Thereafter, we measured the mechanical properties of healing tendons after local myostatin administration. This treatment increased the volume and the contraction of the callus after 8 days, but did not improve its strength. Our results indicate that myostatin plays a positive role in tendon maintenance and that exogenous protein administration stimulates proliferation and growth of early repair tissue. However, no effect on further development towards connective tissue formation was found.

Place, publisher, year, edition, pages
2009. Vol. 27, no 4, 247-254 p.
Keyword [en]
GDF-8; myostatin; follistatin; gene expression; mechanical loading; Achilles tendon
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-20180DOI: 10.1080/08977190903052539OAI: oai:DiVA.org:liu-20180DiVA: diva2:233777
Available from: 2009-09-02 Created: 2009-08-31 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Response to mechanical loading in healing tendons
Open this publication in new window or tab >>Response to mechanical loading in healing tendons
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ruptured tendons heal faster if they are exposed to mechanical loading. Loading creates deformation of the extracellular matrix and cells, which give rise to intracellular signalling, increased gene expression and protein synthesis. The effects of loading have been extensively studied in vitro, and in intact tendons in vivo. However, the response to loading in healing tendons is less known.

The general aim of this thesis was to understand more about the response to mechanical loading during tendon healing. The specific aims were to find out how short daily loading episodes could influence tendon healing, and to understand more about genes involved in tendon healing.

The studies were performed using rat models. Unloading of healing tendons resulted in a weaker callus tissue. This could be reversed to some extent by short daily loading episodes. Loading induced more matrix production, making the tendons thicker and stronger, but there was no improvement in the material properties of the matrix. Lengthening is one potential adversity with early loading, during tendon healing in patients. This was also seen with continuous loading in the rat models. However, short loading episodes did not result in any lengthening, not even when loading was applied during the inflammatory phase of healing. It also appeared as loading once daily was enough to make healing tendons stronger, while loading twice daily with 8 hours interval did not give any additional effect. The strongest gene expression response to one loading episode was seen after 3 hours. The gene expression changes persisted 12 hours after the loading episode but had disappeared by 24 hours. Loading appeared to regulate genes involved in inflammation, wound healing and coagulation, angiogenesis, and production of reactive oxygen species. Inflammation-associated genes were regulated both by continuous loading and by one short loading episode. Inflammation is an important part of the healing response, but too much can be harmful. Loading might therefore have a role in fine-tuning the inflammatory response during healing.

In conclusion, these studies show that short daily loading episodes during early tendon healing could potentially be beneficial for rehabilitation. Loading might have a role in regulating the inflammatory response during healing.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 86 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1247
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70774 (URN)978-91-7393-166-3 (ISBN)
Public defence
2011-09-09, Nils-Holger salen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
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Available from: 2011-09-16 Created: 2011-09-16 Last updated: 2012-03-27Bibliographically approved

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Eliasson, PernillaAndersson, ThereseAspenberg, Per

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Orthopaedics and Sports MedicineFaculty of Health SciencesDepartment of Orthopaedics Linköping
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