RECEPTORS FOR INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II IN OSTEOBLAST-ENRICHED CULTURES FROM FETAL-RAT BONE

Insulin-like growth factors-I and -II (IGF-I and IGF-II) are produced by bone cells and stored in bone matrix, and stimulate bone cell DNA synthesis and type I collagen production. Earlier studies in cells from an assortment of tissues indicate that IGF-I binds to membrane receptors of various relative molecular mass (Mr), whereas IGF-II binds predomi-nantly to the mannose-6-phosphate transferase. In the present studies we have examined the IGF receptor profile in osteoblast- enriched cultures prepared from fetal rat parietal bone. Scat- chard binding kinetics with either125I-IGF-I or125I-IGF-II were curvilinear, indicating high and low affinity receptor classes for each ligand. Chemical cross-linking and polyacrylamide gel analysis revealed that125I-IGF-I bound at Mr 130, 000, 240, 000, and 260, 000, whereas126I-IGF-II bound predominantly at Mr 240.0. Unlabeled IGF-I displaced125I-IGF-I with high affinity at Mr 260, 000 and 130, 000 and with lower affinity at Mr 240, 000. Unlabeled IGF-II preferentially displaced either radioactive ligand at Mr 240, 000, but at high concentrations displaced125I- IGF-I at all binding sites. Furthermore, mannose-6-phosphate enhanced binding by both125I-IGF-I and125I-IGF-II at Mr 240.0, and antibody to the rat IGF-II receptor prevented binding only at this location. The relative affinities of IGF-I and IGF-II for the primary IGF-I receptor correlate with their ana-bolic activities in bone cultures and suggest that the IGF-I receptor mediates the growth-promoting effects of both agents in bone. © 1990 by The Endocrine Society.