Search

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., Highlights • Tnmd is a mechanosensitive gene and its protein is co-localized with collagen I fibers in the ECM of tendons. • Tnmd knockout mice fail in endurance running tests, a phenotype that worsens with training. • Tnmd knockout tendons had significantly thicker and stiffer collagen I fibers and altered crosslinking gene expression. We performed a multidisciplinary approach to decipher the role of tenomodulin, a gene marker for the mature tendon lineage, in tendon functional performance. Loss-of-function in mice led to significantly inferior endurance running and detailed analyses revealed that tenomodulin is involved in the regulation of collagen I fiber structural and biomechanical properties in response to exercise. Our study expands the current view on the complex structural-functional relationships of tendon tissues, and tenomodulin expression levels may indicate whether an individual is suitable for a certain sport.