INTACT BUT NOT TRUNCATED INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 (IGFBP-3) BLOCKS IGF-I-INDUCED STIMULATION OF OSTEOBLASTS - CONTROL OF IGF SIGNALING TO BONE-CELLS BY IGFBP-3-SPECIFIC PROTEOLYSIS

IGFBP-3 is the predominant IGFBP in serum and the major IGFBP secreted by osteoblasts. Native and recombinant IGFBP-3 and a truncated form lacking the carboxyterminal third were tested for their effects on 2 osteoblastic cell lines. Intact but not truncated IGFBP-3 blocked IGF I-stimulated DNA and glycogen synthesis. Inhibition was dose-dependent and found whenever the concentration of intact IGFBP-3 exceeded the concentration of IGF I. Truncated IGFBP-3 appears to result from proteolytic cleavage and does occur in vivo. The loss of inhibition by IGFBP-3 may be regulated at the site of IGF target cells and thus be essential for IGF I-induced osteoblast growth. © 1991.