REGULATION OF GROWTH PLATE CARTILAGE DEGRADATION INVITRO - EFFECTS OF CALCIFICATION AND A LOW-MOLECULAR-WEIGHT ANGIOGENIC FACTOR (ESAF)

Endothelial cell stimulating angiogenic factor (ESAF) is an activator of matrix metalloproteinases, including latent collagenase, and is released by chondrocytes during calcification. ESAF, added to cultured growth plate chondrocytes, elicited a time-dependent, 2.4-fold increase in matrix lysis (compared with 30% for IL-1). Matrix breakdown was suppressed by addition of tissue inhibitor of metalloproteinase (TIMP). Although calcification has been previously reported to stimulate ESAF production, no corresponding increase in cartilage lysis was seen in the present study. However, the level of ESAF that cultures produce during calcification is many times less than that added to the cultures in this series of experiments. We conclude that ESAF can produce dramatic increases in cartilage breakdown (apparently by activation of latent enzymes), but only at levels in excess of those stimulated by calcification. This indicates that ESAF may operate in concert with other initiators, perhaps from the invading endothelial cells.