Print

Temporomandibular joint (TMJ) movement results in shearing and frictional loads that are endured by an articular disc separating the upper and lower joint cavities filled with synovial fluid. As in other synovial joints, the fluid contains boundary lubricants including hyaluronic acid (HA) and lubricin, which are produced by superficial cell layers of articulating surfaces. Therefore, pathological adhesions between the disc and the flanking articulating surfaces, deterioration of boundary lubricants with age, and other insults likely play major roles in TMJ diseases both in childhood and adulthood. Despite these clinically important pathologies, the molecular mechanisms by which the TMJ establishes and maintains structural and functional integrity remain largely unknown. We found that Indian hedgehog (Ihh) is a secreted signaling factor essential for TMJ formation. Conditional ablation of Ihh at postnatal stage in experimental disease models caused a significant reduction in lubricin gene expression and disc adhesions. Thus, our central hypothesis is that Ihh signaling is required for both TMJ formation and postnatal maintenance of joint integrity. This project will provide novel, important and far-reaching information on TMJ formation and long term function and, in particular, the roles of hedgehog signaling and its effectors in establishing the structural organization of the joint and sustaining disc and lubricant function. Our rescue experiments should provide a proof-of-principle that TMJ defects, including disc adhesions, are amenable to therapeutic intervention.