Long term objectives for studying cartilage repair and regeneration are to elucidate the cellular and molecular events that lead to repair of fibrocartilage in the TMJ during adaptation to normal and pathological loading. Specifically, aims for this proposal include, first, study the optimal and destructive magnitudes and frequencies of cyclic tensile strain (CTS) for repair and break down of TMJs. Second, examine effects of CTS on the wnt-pathway in inflamed fibrochondrocytes. Third, examine the results of CTS on N-cadherin regulation in inflamed fibrochondrocytes. Since the wnt signaling pathway is central to chondrogenesis, once understood, this pathway can be exploited for the development of appropriate therapeutic interventions/regimens to augment repair in TMJDs. As a first step in this direction, proposed Aim # 1 will examine the magnitudes (3%, 6%, 9%, 12%, 15%, 20%) and frequencies (0.005 Hz to 0.5 Hz) of CTS.
Aim # 2 will examine the effects of CTS on the expression of mRNA, proteins and phosphorylation for various Wnt proteins and signaling molecules.
Aim #3 will investigate the CTS regulation on N-cadherin, N-cadherin- associated beta-catenin, and beta-catenin nuclear translocation.
