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
S. Kanzaki et al., 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, Journal of bone and mineral research, 10(6), 1995, pp. 854-858
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).