V. Gangji et al., INSULIN-LIKE-GROWTH-FACTOR-II PROMOTER EXPRESSION IN CULTURED RODENT OSTEOBLASTS AND ADULT-RAT BONE, Endocrinology, 139(5), 1998, pp. 2287-2292
Insulin-like growth factor (IGF)-II stimulates bone formation by incre
asing the replication of cells of the osteoblastic lineage and by enha
ncing the differentiated function of the osteoblast. Although IGF-II i
s synthesized by skeletal cells, little is known about the mechanisms
involved and its regulation by growth factors. IGF-II expression is ti
ssue specific and is developmentally regulated, in the present study,
we examined the expression of IGF-II in fetal rat, newborn mouse and M
C3T3-E1 osteoblastic (Ob) cells, and in adult rat calvariae. We also d
etermined mechanisms involved in the regulation of IGF-II by platelet-
derived growth factor (PDGF) BB, fibroblast growth factor-2 (FGF-2), a
nd transforming growth factor (TGF)beta 1. Northern analysis revealed
IGF-II transcripts of 3.6 and 1.2 kb in osteoblastic cells and adult r
at calvariae. Ribonuclease (RNase) protection assay using probes speci
fic to the three known IGF-II promoters, P1, P2, and P3, demonstrated
messenger RNA (mRNA) expression driven by P3 in osteoblasts and adult
rat calvariae, but no expression of P1 or P2 transcripts. PDGF BB, FGF
-2, and TGF beta 1 inhibited the expression of IGF-II P3 mRNA by 50%.
PDGF BE, FGF-2, and TGF beta 1 also decreased the rates of IGF-II tran
scription in rat Ob cells as determined by nuclear run-on assays and d
id not modify the decay of IGF-II in transcriptionally arrested rat Ob
cells. In conclusion, the synthesis of IGF-II in osteoblastic cells a
nd in adult rat calvariae is driven by IGF-II P3 and is regulated by s
keletal growth factors acting at the transcriptional level using the I
GF-II P3.