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Tenomodulin is Required for Tendon Endurance Running and Collagen I Fibril Adaptation to Mechanical Load

Dex, Sarah and Alberton, Paolo and Willkomm, Lena and Soellradl, Thomas and Bago, Sandra and Milz, Stefan and Shakibaei, Mehdi and Ignatius, Anita and Bloch, Wilhelm and Clausen-Schaumann, Hauke and Shukunami, China and Schieker, Matthias and Docheva, Denitsa (2017) Tenomodulin is Required for Tendon Endurance Running and Collagen I Fibril Adaptation to Mechanical Load. EBioMedicine, 20. pp. 240-254. ISSN 2352-3964

Abstract

Tendons are dense connective tissues that attach muscles to bone with an indispensable role in locomotion because of their intrinsic properties of storing and releasing muscle- generated elastic energy. Tenomodulin (Tnmd) is a well-accepted gene marker for the mature tendon/ligament lineage and its loss-of -function in mice leads to a phenotype with distinct signs of premature aging on tissue and stem/progenitor cell levels. Based on these findings, we hypothesized that Tnmd might be an important factor in the functional performance of tendons. Firstly, we revealed that Tnmd is a mechanosensitive gene and that the C-terminus of the protein co-localize with collagen I-type fibers in the extracellular matrix. Secondly, using an endurance training protocol, we compared Tnmd knockout mice with wild types and showed that Tnmd deficiency leads to significantly inferior running performance that further worsens with training. In these mice, endurance running was hindered due to abnormal response of collagen I cross-linking and proteoglycan genes leading to an inadequate collagen I fiber thickness and elasticity. In sum, our study demonstrates that Tnmd is required for proper tendon tissue adaptation to endurance running and aids in better understanding of the structural-functional relationships of tendon tissues.

Item Type: Article
Keywords: Atomic force microscopy Collagen I crosslinking Knockout mouse model Running tests Tendons Tenomodulin
Date Deposited: 25 Nov 2017 00:45
Last Modified: 25 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/32663

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