Role of Smad3 and S1P Signaling in Mandibular Condylar Cartilage Homeostasis

Osteoarthritis (OA), the most common degenerative joint disease, results from an imbalance between chondrocyte-controlled anabolic and catabolic processes. OA is characterized by progressive degradation of components of the Extracellular Matrix (ECM) within the articular cartilage, correlated with secondary inflammation. Several studies had investigated the morphological and biochemical changes during OA progression. However, a comprehensive study of the OA pathogenesis still remains to be elucidated to find the best therapy for OA. In this review, recent advances in our understanding of the mechanisms of action of Sphingosine 1-phosphate (S1P) and Smad3 independently and in relation to Temporomandibular Joint Osteoarthritis (TMJ-OA) will be discussed. S1P receptors are expressed on the cell surface and are internalized upon binding of the bioactive lipid, S1P, as part of the migratory response. Meanwhile, Smad3 is an intracellular signaling molecule that mediates signaling from transforming growth factor-β (TGF-β) and activin receptors. Crosstalk between the TGF-β/Smad3 and S1P/S1P3 signaling pathways regulates cell motility and apoptosis in chondrocyte cells. Thus, Smad3/S1P3 signaling in chondrocytes may be responsible for the development of TMJ-OA, and the potential for these proteins to represent targets for the treatment of TMJ-OA warrants further study.