EVIDENCE THAT HUMAN BONE-CELLS IN CULTURE SECRETE INSULIN-LIKE GROWTH-FACTOR (IGF)-II AND IGF BINDING PROTEIN-3 BUT NOT ACID-LABILE SUBUNITBOTH UNDER BASAL AND REGULATED CONDITIONS

Insulin-like growth factors (IGFs) are found in human circulation pred ominantly as part of a growth hormone (GH)-dependent complex of 125-15 0 KD, which is composed of three subunits: IGF-I or IGF-II, an acid st able IGF binding protein (IGFBP)-3, and an acid labile subunit (ALS). Although recent studies demonstrate that a number of cell types in cul ture secrete IGFs and IGFBP-3, very little is known with regard to the origin of circulating ALS, To test the hypothesis that human bone cel ls (HBCs), which produce abundant amounts of IGF-II and IGFBP-3, also produce ALS, we measured the IGF-I, lGF-II IGFBP-3, and ALS levels usi ng specific radioimmunoassays (RIAs) in the conditioned medium (CM) of untransformed normal HBCs and SaOS-2 osteosarcoma cells treated with various effecters (IGF-II, osteogenic protein-1 [OP-1, bone morphogene tic protein-7] and human GH) for 48 h. No detectable levels (<3 ng/ml) of ALS were found in the CM of various HBC types under basal conditio ns. In contrast, CM collected hem liver explants in culture contained significant amount of AILS prepared and assayed under identical condit ions. The IGF-I level was also undetectable in the (SM of various HBC types. In the IGF-II (3, 30 ng/ml)-treated HBC CM, the IGFBP-3 level w as increased in a dose-dependent manner but neither IGF-I nor ALS coul d be detected. In the SaOS-2 cell culture, OP-1 (1, 100 ng/ml) increas ed both IGF-II and IGFBP-3 secretion but neither ALS nor IGF-I secreti on. Treatment of HBCs with GH (1, 10, 100 ng/ml) had no significant ef fect on the secretion of either IGF-I, IGF-II, IGFBP-3, or ALS. The le vel of 3[GF-II in the CM of various HBC types correlated positively wi th that of IGFBP-3 (r = 0.84). From these results, we conclude that th e production of ALS and IGFBP-3 are not concomitantly regulated by the same effecters in HBCs. The finding of this study together with the p revious findings that GH regulates ALS secretion in liver cells sugges t that the primary functions of IGFs produced in the bone and liver ma y be different (i.e., local versus endocrine effects).