Human alpha(2)-macroglobulin is an osteogenic growth peptide-binding protein

The osteogenic growth peptide (OGP) is a 14mer mitogen of osteoblastic and fibroblastic cells. Physiologically, OGP is present in high abundance in human and other mammalian sera. Most of the serum OGP is complexed noncovalently to heat sensitive, high molecular weight OGP-binding proteins (OGPBPs). Changes in serum OGP levels that follow bone marrow ablation and the low doses of exogenous OGP required for the stimulation of bone formation suggest a regulatory role for the OGPBPs. In the present work, the OGP binding activity was monitored by competitive binding to [3-I-125(Tyr(10)]sOGP and the corresponding complexes were demonstrated on nondenaturing cathodic polyacrylamide gel electrophoresis. We show that OGP binds to both native and activated human plasma alpha(2)-macroglobulin (alpha(2)M). alpha(2)M was also immunoidentified in reduced and nonreduced SDS-polyacrylamide gel electrophoresis of OGP-affinity purified plasma-derived proteins; immunoreactive OGP was detected in commercial preparations of both forms of alpha(2)M; OGP was purified to homogeneity from the commercia! preparation of activated alpha(2)M. In MC3T3 El cells, native alpha(2)M, at concentrations <50 ng/mL, had a substantially increased mitogenic effect in the presence of synthetic, native-like, OGP (sOGP). Similar amounts of activated alpha(2)M inhibited the sOGP proliferative effect, These results suggest that the native alpha(2)M enhances the immediate availability of OGP to its target cells, Activated alpha(2)M may participate in the removal of OGP from the system.