Discovery of fibrotic intervertebral disc in mice

Intervertebral discs are crucial to spine flexibility and stability during locomotion, but the mechanism of their mechanoadaptation to stress remains inadequately elucidated. We discovered spontaneous collagenesis in discs at the tail base in mice occurring from 14 days post-natal development. These discs termed as type C, differ from typical discs by exhibiting intensive collagen II and reduced aggrecan deposition contributing to the stiffening of the extracellular matrix (ECM), without typical degenerative markers. The reinforced mechanical properties enable type C discs to withstand high mechanical stress during flexion. Further analysis revealed that type C discs experience a turnover in cell composition, with the emergence of Procr+ progenitor cells and depletion of notochord cells. We demonstrated the essential role of mechanical stress in type C disc formation, suggesting a mechanoadaptive process rather than a pathological condition. Mechanistically, we identified TRPV4, as pivotal factors in collagen II synthesis in type C discs, highlighting the role of mechanotransduction in this adaptation. Our findings introduce a novel mechanoadaptive process of intervertebral disc by orchestrating collagenesis, advancing understanding of diverse disc functions in spine development and homeostasis, thereby providing insights for leveraging this mechanism to address spinal disorders.