Epiphyseal growth plate cartilage and chondrocytes in mineralising cultures produce a low molecular mass angiogenic procollagenase activator.

Abstract

We have investigated one aspect of the biochemical control of angiogenesis in the mammalian growth plate. This is the first report of an angiogenic compound from normal growing skeletal tissue. The active agent was indistinguishable from ESAF (endothelial cell-stimulating angiogenic factor), previously identified from tumour, retina and synovial fluid. 1. Using a procollagenase activation assay, ESAF was detected in low molecular weight extracts of growth plate cartilage from two species (foetal calf and young rabbit). ESAF content declined with increasing age of the foetal calf growth plate cartilage. 2. Rabbit growth plate chondrocytes in high density culture also produced ESAF 24-48 h after calcification of the culture. Inhibition of alkaline phosphatase in these cultures reduced the stimulation of ESAF production. These findings suggest that ESAF production occurs as a stage in chondrocyte differentiation which is linked with the onset of matrix calcification. A model is proposed for the control of angiogenesis in the growth plate.