CHARACTERIZATION, REGULATION, AND FUNCTION OF SPECIFIC CELL-MEMBRANE RECEPTORS FOR INSULIN-LIKE GROWTH-FACTOR-I ON BONE ENDOTHELIAL-CELLS

It is now widely accepted that insulin-like growth factor-I (IGF-I) ha s a local regulatory role in bone remodeling. IGF-I has also been demo nstrated to regulate proliferation of bone-derived endothelial cells. Such studies suggest a role of IGF-I in skeletal angiogenesis. Using B BE cells, a bovine bone endothelial cell line, we characterized the ki netics and chemical properties of IGF-I receptors and examined the eff ect of IGF-I on bone endothelium migration. Two classes of binding sit es with high affinity for IGF-I were detected by binding experiments o n bone endothelial cells. Both competition analyses and cross-linking studies revealed the presence of type I IGF receptor in bone endotheli al cells. Moreover, these cells produced and released authentic IGF-I into the medium, as evidenced by radioimmunoassay analyses of gel-filt ered conditioned media. Both IGF-I binding capacity and release decrea sed either with increases in cell number or after treatment with 17 be ta-estradiol (17 beta E(2)) and parathyroid hormone (PTH). Both hormon es also inhibited chemotactic responses of bone endothelial cells to I GF-I. Taken together, these results strongly suggest that IGF-I, a gro wth factor that promotes the proliferation of various bone cell types, also induces growth and chemotactic responses in bone endothelium act ing through the type I IGF receptor. This may be part of a generalized response of bone cells to IGF-I that facilitates cell migration.