INSULIN-LIKE-GROWTH-FACTOR (IGF)-BINDING PROTEIN-5-(201-218) REGION REGULATES HYDROXYAPATITE AND IGF-I BINDING

Insulin-like growth factor-binding protein-5 (IGFBP-5), the major bone IGFBP, modifies the biological activity of IGFs within the osteoblast ic pericellular environment. Because glycosaminoglycans modulate IGFBP -5 binding to osteoblast organic extracellular matrix (ECM), we assess ed whether the heparin binding domain of IGFBP-5, IGFBP-5-(102-218), m odifies the interaction of IGFBP-5 with the inorganic bone ECM hydroxy apatite (HA). Synthetic IGFBP-5-(201-218) peptide increased the bindin g of IGFBP-5 to HA as well as the binding of IGF-I to HA-bound IGFBP-5 . This action was specific for the heparin-binding domain, because IGF BP-5-(130-138), IGFBP-5-(138-152), and IGFBP-5-(1-169) were without ef fect. IGFBP-5-(201-218) was found to bind directly to IGFBP-5 and caus e a threefold enhancement of the IGF-I binding affinity for IGFBP-5, w hether IGFBP-5 was bound to HA or was in a matrix-free fluid phase. He parin inhibited the binding of IGFBP-5 to HA and blocked the interacti on of IGFBP-5 with IGFBP-5-(201-218) in the fluid phase, suggesting th at the primary heparin-binding domain of IGFBP-5 specifically enhances the binding of IGFBP-5 to HA and increases IGF-I binding to IGFBP-5.