Poster 4: RAGE, inflamation, and the temporomandibular joint

Abstract

Background: Temporomandibular joint disorders (TMDs) represent a common cause of facial pain. Although the etiology of TMD is not fully elucidated, histologic and arthroscopic studies suggest that inflammation is evident and similar to osteoarthritis of other synovial joints. Evidence suggests that chronic mechanical trauma to the temporomandibular joint (TMJ) triggers generation of reactive oxidant species, resulting in the formation of advanced glycation end products (AGEs). Engagement of AGEs by their signal transduction receptor, RAGE (receptor for AGE), initiates specific signaling pathways. AGE-RAGE interaction activates a range of inflammatory cells and generates cytokines at immune/inflammatory foci. Transgenic mice overexpressing human TNF-alpha (tghTNF-alpha) display sustained inflammation in synovial joints, including the TMJ, leading to synovitis and degeneration of the joint, consequent to upregulation of multiple cytokines and key MMPs. In this model, multiple pathologic and molecular properties are shared with those observed in human TMDs. We hypothesize the tghTNF-alpha mouse is appropriate to study the biochemical cascade in TMDs. We examined the presence of RAGE in human synovial biopsy samples and in a transgenic mouse overexpressing human TNF-alpha, where progressive inflammation and destruction of the TMJ occurs.