Wnt signaling: a promising target for osteoarthritis therapy

Osteoarthritis (OA) is the most common joint disease worldwide and a leading cause of disability. Characterized by degradation of articular cartilage, synovial inflammation, and changes in periarticular and subchondral bone, OA can negatively impact an individual’s physical and mental well-being. Recent studies have reported several critical signaling pathways as key regulators and activators of cellular and molecular processes during OA development. Wnt signaling is one such pathway whose signaling molecules and regulators were shown to be abnormally activated or suppressed. As such, agonists and antagonists of those molecules are potential candidates for OA treatment. Notably, a recent phase I clinical trial (NCT02095548) demonstrated the potential of SM04690, a small-molecule inhibitor of the Wnt signaling pathway, as a disease-modifying oseoarthritis drug (DMOAD). This review summarizes the role and mechanism of Wnt signaling and related molecules in regulating OA progression, with a view to accelerating the translation of such evidence into the development of strategies for OA treatment, particularly with respect to potential applications of molecules targeting the Wnt signaling pathway.