Endocrinology, Vol 126, 39-44, Copyright © 1990 by Endocrine Society

ARTICLES

Receptors for insulin-like growth factors-I and -II in osteoblast- enriched cultures from fetal rat bone

M Centrella, TL McCarthy and E Canalis
Research Laboratory, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105.

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 predominantly 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. Scatchard binding kinetics with either 125I-IGF-I or 125I-IGF-II were curvilinear, indicating high and low affinity receptor classes for each ligand. Chemical cross-linking and polyacrylamide gel analysis revealed that 125I-IGF-I bound at Mr 130,000, 240,000, and 260,000, whereas 125I- IGF-II bound predominantly at Mr 240,000. Unlabeled IGF-I displaced 125I-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 displaced 125I-IGF-I at all binding sites. Furthermore, mannose-6- phosphate enhanced binding by both 125I-IGF-I and 125I-IGF-II at Mr 240,000, 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 anabolic activities in bone cultures and suggest that the IGF-I receptor mediates the growth- promoting effects of both agents in bone.

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