Signalling interaction between -catenin and other signalling molecules during osteoarthritis development

Osteoarthritis (OA) is the most prevalent disorder of synovial joint affecting multiple joints. In the past decade, we have witnessed conceptual switch of OA pathogenesis from a 'wear and tear' disease to a disease affecting entire joint. Extensive studies have been conducted to understand the underlying mechanisms of OA using genetic mouse models and ex vivo joint tissues derived from individuals with OA. These studies revealed that multiple signalling pathways are involved in OA development, including the canonical Wnt/beta-catenin signalling and its interaction with other signalling pathways, such as transforming growth factor beta (TGF-beta), bone morphogenic protein (BMP), Indian Hedgehog (Ihh), nuclear factor kappa B (NF-kappa B), fibroblast growth factor (FGF), and Notch. The identification of signalling interaction and underlying mechanisms are currently underway and the specific molecule(s) and key signalling pathway(s) playing a decisive role in OA development need to be evaluated. This review will focus on recent progresses in understanding of the critical role of Wnt/beta-catenin signalling in OA pathogenesis and interaction of beta-catenin with other pathways, such as TGF-beta, BMP, Notch, Ihh, NF-kappa B, and FGF. Understanding of these novel insights into the interaction of beta-catenin with other pathways and its integration into a complex gene regulatory network during OA development will help us identify the key signalling pathway of OA pathogenesis leading to the discovery of novel therapeutic strategies for OA intervention. The Wnt/beta-catenin signalling pathway plays critical roles in OA pathogenesis. Abnormal beta-catenin signalling in chondrocytes, synovial fibroblast and osteocytes leads to OA-like structural changes, such as progressive cartilage lesion, synovitis and sclerosis of subchondral bone and osteophyte formation.image