Regional FDL tendon properties are regulated by biglycan in a collagen VI-independent manner

Healthy tendon is associated with organized and aligned extracellular matrix (ECM) that becomes disorganized with disease, yet the mechanisms and pathogenesis of tendon disease remain poorly understood. Tendons that "wrap-around" joints, such as the flexor digitorum longus (FDL) tendon, contain a unique ECM that shares similarities with diseased tendons, which can be leveraged to study tendon cell biology across distinct loading environments. The pericellular matrix (PCM) is a critical matrix structure that is understudied in tendon and is likely involved in tendon mechanosensation and homeostasis. Two components of the tendon PCM, biglycan and collagen VI, are known regulators of tendon function and are implicated in tendon disease. Given the implication of PCM molecules in regulating tendon properties, this work sought to define the regional development of a murine wrap-around tendon, how biglycan influences these regional properties, and the extent to which these mechanisms involve collagen VI. Gene expression and histological analyses demonstrated regional divergence in FDL tendon properties by P14. While biglycan knockout did not result in broad disruptions to gene expression or the behavior of <i>Scx</i>+ or <i>Col6a1</i>+ cells, several genes were dysregulated with biglycan deficiency. These changes corresponded with inferior mechanical properties in biglycan-deficient tendons. This work defines the development of regional FDL tendon properties and demonstrates that biglycan knockout impacts these regional properties through a collagen VI-independent mechanism. Results from this work provide understanding of biglycan regulation in tendon and lay the foundation for future work researching tendon mechanosensitive mechanisms.