In conclusion, we demonstrated, for the first time to our knowledge, that the BMP-2-induced Wnt/β-catenin signaling pathway activation through LRP-5 induces chondrocyte catabolic action and hypertrophy, providing thus novel and direct evidence on the role of BMP-2 mediated by Wnt/β-catenin signaling in osteoarthritis progression. This evidence concerns the gene LRP5 and osteoarthritis.