The release and activation of transforming growth factor beta 2 associatedwith 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 eve nts in endochondral formation. We have shown that the hypertrophy and apopt osis of chick chondrocytes in culture is associated with the release and ac tivation of transforming growth factor beta2 (TGF-beta2). Supplementation o f the culture medium with agents that influenced the maintenance of hypertr ophic differentiation also influenced the release of TGF-beta2. A large pro portion of the TGF-beta2 released from the cells was shown to be in an acti ve form-particularly TGF-beta2 associated with the support matrix. Inhibiti on of apoptosis with a broad-spectrum caspase inhibitor inhibited activatio n 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 as sociation 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.