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Mechanical load and BMP signaling during tendon repair: A role for follistatin?
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.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
2008 (English)In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 466, no 7, p. 1592-1597Article in journal (Refereed) Published
Abstract [en]

Healing of the rat Achilles tendon is sensitive to mechanical loading, and the callus strength is reduced by 3/4 after 14 days, if loading is prevented. Exogenous GDFs stimulate tendon healing. This response is influenced by loading: without loading, cartilage and bone formation is initiated. This implies BMP signaling is crucial during tendon healing and influenced by mechanical loading. We therefore asked if mechanical loading influences the gene expression of the BMP signaling system in intact and healing tendons, and how the BMP signaling system changes during healing. The genes were four BMPs (OP-1/BMP-7, GDF-5/CDMP-1/BMP-14, GDF-6/CDMP2/BMP-13, and GDF-7/CDMP-3/BMP-12), two receptors (BMPR1b and BMPR2), and the antagonists follistatin and noggin. The Achilles tendon was transected in rats and left to heal. Half of the rats had one Achilles tendon unloaded by injection of Botox in the calf muscles. Ten tendons were analyzed before transection and for each of four time points. All genes except noggin were expressed at all points, but followed different patterns during healing. Loading strongly decreased the expression of follistatin, which could lead to increased signaling. The BMP system appears involved in tendon maintenance and healing, and may respond to mechanical loading.

Place, publisher, year, edition, pages
2008. Vol. 466, no 7, p. 1592-1597
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-45883DOI: 10.1007/s11999-008-0253-0OAI: oai:DiVA.org:liu-45883DiVA, id: diva2:266779
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
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. p. 86
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
Supervisors
Available from: 2011-09-16 Created: 2011-09-16 Last updated: 2020-02-03Bibliographically approved

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Eliasson, PernillaFahlgren, AnnaAspenberg, Per

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