Active role of chondrocyte apoptosis in endochondral ossification.

Endochondral ossification involves an ordered progression from cell division through hypertrophic differentiation to cell death. The apoptotic nature of chondrocyte death was first suggested by characteristic changes in morphology; and more recently by the pattern of DNA fragmentation and other characteristic features of apoptosis. In situ detection, although controversial, suggests that DNA fragmentation probably does not occur until late in hypertrophic differentiation. From observations of key features of apoptosis, including activation of the caspase cascade, changes in mitochondrial function, and expression of apoptosis inhibitors, the commitment of chondrocytes to apoptosis, appears to occur very early in hypertrophic differentiation. It is proposed that these changes produce effects that go far beyond the process of cell death and exert a focal influence on the endochondral ossification processes occurring in the microenvironment of the growth cartilage vascular interface. Endochondral ossification processes mediated by chondrocyte apoptosis may include intracellular calcium accumulation and release; matrix calcification; matrix resorption; maintenance of growth plate homeostasis; attraction of blood vessels and osteoblast precursors; and stimulation of bone formation.