Type VI Collagen Regulates Mineralization in TMJ Health and Disease.

This study investigates the role of pericellular Type VI Collagen (ColVI) in maintaining the integrity and function of temporomandibular joint (TMJ) cartilage and its involvement in TMJ osteoarthritis (TMJ OA). Type VI Collagen is a triple helix made of a1, a2, and a3 chains. Knocking out one chain ensures that the collagen is not released in the extracellular matrix (ECM). Hence we utilized Col6a1 chain knocked-out mice and explored the effects of Type VI collagen deficiency through various techniques such as RT-qPCR, Western blot, immunohistochemistry, and microcomputed tomography (μCT). This is done to assess gene expression, protein processing, and bone structure in Col6a1ko mice. Additionally, as Type VI Collagen is both a signaling and structural molecule, we aimed to determine whether ColVI affects the ECM through signaling or mechanotransduction. The results revealed that the absence of the Col6α1 chain leads to suppressed biomineralization, dysfunctional endochondral ossification, and abnormal ERK signaling. μCT analysis validated structural changes, highlighting the critical role of ColVI in maintaining bone density and architecture. Col6a1 knockout mice exhibited significant alterations in bone structure, such as reduced bone volume, decreased trabecular numbering, and increased trabecular spacing causing compromised bone integrity, particularly under osteoarthritic conditions. The findings underscore the importance of ColVI in preserving cartilage integrity and suggest its potential as a therapeutic target for mitigating cartilage degradation and improving joint health in TMJ OA.