Abstract
The collagenous matrix of tendon provides mechanical integrity, allowing the tissue to withstand large tensile forces. While collagen I-containing fibrils provide the major backbone of the tendon matrix, interactions with other collagen types are critical for matrix formation and maintenance. Of these less abundant collagens, collagen V regulates fibril nucleation and lateral growth. In previous work, mouse models with reduced collagen V production recapitulated the musculoskeletal complications of Classic Ehlers-Danlos Syndrome in tendon development and healing, demonstrating altered structure and inferior mechanical properties. However, the roles of collagen V in homeostasis of mature, healthy tendon remain unknown. Therefore, this study evaluated the role of collagen V in maintaining tendon homeostasis using inducible knockdown of Col5a1in mature mice. After 30 days of reduced collagen V expression, patellar tendons demonstrated changes consistent with impaired matrix remodeling. Extracellular matrix and matrix remodeling genes were differentially expressed, and the distribution of fibril diameters was significantly altered with reduced expression of collagen V. The functional consequence of collagen V knockdown was demonstrated using mechanical testing, which revealed a reduction in failure properties, although sub-failure properties such as stiffness and modulus were not affected. Interestingly, differences between these results and prior studies on the impact of collagen V on development or healing suggest a distinct role for collagen V in maintaining the properties of mature, healthy tendon. In summary, this study demonstrated that collagen V is essential for homeostasis of adult tendons through maintenance of the collagenous matrix.