Production of endothelial cell stimulating angiogenesis factor (ESAF) by chondrocytes during in vitro cartilage calcification

The aim of this study was to identify the stimulus for production of the latent collagenase and angiogenic activator ESAF by growth plate chondrocytes. Stimulation correlated most closely with matrix calcification. Alkaline phosphatase was necessary for calcification (and so stimulation of ESAF production) but we could find no evidence for a direct link with ESAF production. ESAF production was also stimulated by addition of preformed mineral to non-calcified cultures but was inhibited by dexamethasone. Protein synthesis was necessary for the stimulation of ESAF production by calcification, though ESAF is not itself a protein. Based on these findings we suggest that chondrocytes, at a suitable stage of maturation in the growth plate, are stimulated to produce ESAF by the proximity of crystals in the matrix. Stimulation, which may consist of the induction of an enzyme or transport protein, leads to the release of this potent activator of collagenolysis as part of the angiogenic cascade.