Endochondral ossification is an essential process for skeletal development, in which chondrocyte undergoes apoptosis and induces mineralization after terminal differentiation. The apoptosis of chondrocyte is accompanied by marked accumulation of extracellular phosphate ions, which up-regulates the concentration of intra-cellular phosphate ions and leads to the activation of pro-apoptotic factors. The mineralization of chondrocyte is regulated by the orchestrated process mediated by intra-vesicular phosphate ion production by PHOSPHO1, phosphate ion influx into matrix vesicles through Pit-1, and the functions of TNAP and NPP1 that controls pyrophosphate to phosphate ratio in the extra-vesicular progression of mineralization. The apoptosis and mineralization of chondrocyte are related to not only skeletal development but also pathological conditions such as rickets/osteomalacia and osteoarthritis.