The release and activation of transforming growth factor β2 associated with apoptosis of chick hypertrophic chondrocytes

The apoptosis of hypertrophic chondrocytes at the interface between growth cartilage and invading vessels is at the center of a series of critical events in endochondral formation. We have shown that the hypertrophy and apoptosis of chick chondrocytes in culture is associated with the release and activation of transforming growth factor beta2 (TGF-beta2). Supplementation of the culture medium with agents that influenced the maintenance of hypertrophic differentiation also influenced the release of TGF-beta2. A large proportion of the TGF-beta2 released from the cells was shown to be in an active form-particularly TGF-beta2 associated with the support matrix. Inhibition of apoptosis with a broad-spectrum caspase inhibitor inhibited activation of the matrix-associated TGF-beta2. However, inhibition of apoptosis did not diminish the release of TGF-beta2. Release of TGF-beta2 by chondrocytes at a late stage of their terminal differentiation and its activation in association with apoptosis may provide a mechanism controlling the processes of vascular invasion of growth cartilage and the deposition of bone matrix on nearby cartilage remnants.