N. Franchimont et al., INTERLEUKIN-6 WITH ITS SOLUBLE RECEPTOR ENHANCES THE EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I IN OSTEOBLASTS, Endocrinology, 138(12), 1997, pp. 5248-5255
Interleukin (IL)-6, a cytokine produced by skeletal cells and known to
increase bone resorption, has mitogenic effects for bone cells, pos s
ibly by regulating the synthesis of other local factors. We tested the
effects of IL-6 and its soluble receptor (IL-6sR) on the expression o
f insulin-like growth factor (IGF)-I and IGF-II in cultured osteoblast
-enriched cells from fetal rat calvariae (Ob cells). IL-6 did not modi
fy IGF-I messenger RNA (mRNA) levels, but when tested in the presence
of IL-6sR, IL-6 at 1 to 100 ng/ml increased IGF-I transcripts by up to
3.2-fold after 24 h. IL-6sR caused a small increase in IGF-I mRNA lev
els when tested alone. IL-6 and IL-6sR increased immunoreactive IGF-I
levels by 2.4-fold after 24 h and 6.4-fold after 48 h. Cycloheximide p
revented, and indomethacin markedly decreased, the effect of IL-6 and
IL-6sR on IGF-I mRNA levels, but hydroxyurea did not. IL-6 and IL-6sR
did not alter the decay of IGF-I mRNA in transcriptionally arrested Ob
cells, and the half-life of the predominant 6.5-kb IGF-I transcript w
as about 11 h in control and treated cells. In addition, IL-6 and IL-6
sR increased the levels of IGF-I heterogeneous nuclear RNA. IL-11 also
increased IGF-I mRNA levels, whereas oncostatin M and leukemia-inhibi
tory factor did not. In contrast to their effects on IGF-I, IL-6 and I
L-6sR caused only a modest increase in IGF-II mRNA and polypeptide lev
els. In conclusion, IL-6, in the presence of IL-6sR, increases IGF-I s
ynthesis in Ob cells; this effect may lead to a secondary increase in
bone formation.