Wnt Signaling in Cartilage Development and Degeneration

In adult articular cartilage, the extracellular matrix is maintained by a balance between the degradation and synthesis of matrix components. Chondrocytes that sparsely reside in the matrix and rarely proliferate are the key cellular mediators for cartilage homeostasis. Indications have been found for the involvement of the Wnt signaling pathway in maintaining articular cartilage and deregulation of Wnt signaling was observed in cartilage degeneration. Furthermore, several Wnts have been found to be involved in the subsequent stages of chondrocyte differentiation during development. Even though gene expression and protein synthesis can be activated upon injury, articular cartilage has a limited ability of self-repair and efforts to regenerate articular cartilage are so far not sufficient. Since Wnt signaling was found to be involved in the development and maintenance of cartilage as well as in the degeneration of cartilage, interfering with this pathway might contribute to improving cartilage regeneration. However, most of the studies on elucidating the role of Wnt signaling in these processes were conducted using in vitro or in vivo animal models. Since discrepancies have been found in the role of Wnt signaling in chondrocytes between mouse and human, extrapolation of results from mouse models to the human situation remains a challenge. Elucidation of detailed Wnt signaling functions will provide knowledge to improve cartilage regeneration.