A fine balance between cartilage matrix synthesis and degradation is critical both for the maintenance of articular cartilage function and skeletal development and growth. Disruption of this balance causes abnormalities in skeletal formation and growth and leads to degenerative cartilage diseases, including osteoarthritis and rheumatoid arthritis. Previous studies from this and other laboratories have indicated that Wnt proteins regulate chondrocyte function and behavior and also play important roles in cartilage development and skeletogenesis, from the initial steps of chondrogenesis to the final steps during which calcified cartilage is replaced by bone. Inhibition of Wnt/β -catenin signaling suppresses chondrocyte maturation and endochondral ossification, while activation both inhibits cartilage matrix synthesis and accumulation and impairs growth plate organization and tissue integrity. We found that activation of Wnt/β - catenin signaling strongly stimulated proteoglycan loss from chondrocyte cultures and cartilage explants while upregulated the expression of genes responsible for cartilage matrix degradation. Furthermore, β-catenin accumulates in chondrocytes located in osteoarthritic articular cartilage in a manner similar to that normally occurring in growth plate hypertrophic chondrocytes, suggesting that Wnt/β -catenin signaling is activated in regions where active matrix degradation occurs; thus, Wnt/β -catenin signaling may be a common pathway regulating matrix disruption during endochondral ossification and pathological degeneration of cartilage.
Keywords: Chondrocyte, Wnt, β -catenin, MMPs, osteoarthritis
Rights & PermissionsPrintExport