Constitutive activation of β-catenin led to accelerated cell-transformation from chondrocytes into bone cells, giving rise to osteogenesis in the cartilage. (A) Co-IHC staining with Col 2 in the CA-β-cat MCC displayed a more widespread, denser, but patchy area of chondrocytes, with many more red prechondroblastic cells (arrow) near the MCC surface. (B) Col 1 expression was much higher (arrows) in CA-β-cat MCC (high magnification in lower panel). (C) Many chondrocytes also expressed high level of DMP1, reflecting the accelerated trans-differentiation from chondrocytes into bone cells in CA-β-cat MCC (arrows). (D) Using both conditional deletion and constitutive activation of β-catenin, our study demonstrates the critical role of β-catenin in the direct trans-differentiation of chondrocytes to bone cells during MCC growth. The lack of β-catenin led to a decrease of chondrogenesis and chondrocyte-derived bone cells, accompanied by reduction of subchondral bone volume; the stabilization of β-catenin gave rise to more chondrogenesis and cell trans-differentiation, along with cartilage calcification in MCC.