SERUM FRACTIONS AND RELATED AGONISTS WITH CALCIUM-MOBILIZING ACTIVITYIN THE BOVINE GROWTH-PLATE CHONDROCYTE

Longitudinal growth of bone involves a complex sequence of cellular ev ents in the cartilaginous epiphysis. Whole blood serum has been shown previously to be a potent stimulus to the cells of the growth plate, a s demonstrated by its ability to activate the inositol phosphate-calci um second messenger system, resulting in a rise in intracellular Ca2+. By manipulating the preparation of serum to functionally separate it into its constituent parts, we have shown that the processes of platel et lysis and activation of the clotting cascade are responsible for th e generation of factors that stimulate this signaling mechanism in iso lated bovine growth plate chondrocytes. Through a subsequent trial of bioactive agents generated in these processes, we identified and parti ally characterized several novel agonists of growth plate chondrocytes : adenosine triphosphate and adenosine diphosphate, the purine energy substrates, and bradykinin, the bioactive peptide generated in a side reaction of the clotting cascade, each induces a rise in intracellular Ca2+ via release from intracellular ion stores. Additionally, the thr ee distinct isoforms of platelet-derived growth factor (AA, AB, and BE ), also released on platelet lysis, were compared with respect to thei r ability to stimulate the inositol phosphate-calcium second messenger system in growth plate chondrocytes.