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 abund ance in human and other mammalian sera. Most of the serum OGP is compl exed noncovalently to heat sensitive, high molecular weight OGP-bindin g proteins (OGPBPs). Changes in serum OGP levels that follow bone marr ow ablation and the low doses of exogenous OGP required for the stimul ation of bone formation suggest a regulatory role for the OGPBPs. In t he 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 electrophor esis. We show that OGP binds to both native and activated human plasma alpha(2)-macroglobulin (alpha(2)M). alpha(2)M was also immunoidentifi ed 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 w as purified to homogeneity from the commercia! preparation of activate d alpha(2)M. In MC3T3 El cells, native alpha(2)M, at concentrations <5 0 ng/mL, had a substantially increased mitogenic effect in the presenc e of synthetic, native-like, OGP (sOGP). Similar amounts of activated alpha(2)M inhibited the sOGP proliferative effect, These results sugge st that the native alpha(2)M enhances the immediate availability of OG P to its target cells, Activated alpha(2)M may participate in the remo val of OGP from the system.