Collagenesis orchestrates mechanoadaptive development and homeostasis of intervertebral discs.

Abstract

Intervertebral discs underpin spinal flexibility and stability during locomotion, yet the mechanism guiding their mechanoadaptive development remains inadequately elucidated. Here, we discovered a murine disc type programming spontaneous collagen deposition (collagenesis) within coccygeal regions under heightened mechanical loading, commencing around the 14th day after birth. In contrast to typical discs, these collagen-II-enriched discs (designated as type C) impart resistance to compressive and flexural stresses and lower susceptibility to degeneration. Their development involves a shift featuring emergent chondrogenic cell clusters independent of notochordal lineage and diminished notochord cells. Mechanistically, mechanical unloading inhibited type C disc formation, confirming collagenesis as a mechanoadaptive response. TRPV4 was highly expressed, and its deletion impaired collagenesis, underscoring the critical role of mechanotransduction. Critically, analogous mechanoadaptation programs in developing human lumbar spines demonstrate evolutionary conservation. Our findings reveal a fundamental collagenesis orchestrating mechanoadaptive disc development and lifelong homeostasis, offering insights into spinal function and relevant therapeutic strategies.