Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis

Despite the requirement for Scleraxis-lineage (Scx(Lin)) cells during tendon development, the function of Scx(Lin) cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted Scx(Lin) cells (ScxLin(DTR)) prior to tendon injury and repair surgery and hypothesized that ScxLin(DTR) mice would exhibit functionally deficient healing compared to wild-type littermates. Surprisingly, depletion of Scx(Lin) cells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLin(DTR) mice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult Scx(Lin) cell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.