Nitric oxide mediates 17beta-estradiol-stimulated human and rodent osteoblast proliferation and differentiation.
Oestradiol can stimulate osteoblast activity. Osteoblast function is thought to be regulated by nitric oxide (NO). We hypothesised that the effect of 17beta-oestradiol (17beta-E(2)) on osteoblast activity is mediated by NO. This hypothesis was tested using osteoblasts isolated from human trabecular bone, calvariae of rats, endothelial NO synthase (eNOS) gene-deficient mice, and their wild-type counterparts. Our results show that 17beta-E(2) dose-dependently stimulated proliferation and differentiation of primary human, rat and wild-typeosteoblasts. The presence of N(G)-monomethyl-l-arginine (10(-3) M), an inhibitor of NOS activity, blocked the 17beta-E(2)-(10(-7) M)-induced increases in thymidine incorporation (P < 0.01), alkaline phosphatase activity (P < 0.01) and bone nodule formation (P < 0.01) of wild-type, human and rat osteoblasts, respectively. Moreover, 17beta-E(2) did not induce a response in eNOS gene-deficient osteoblasts. 17beta-E(2) also increased total eNOS enzyme expression in rat osteoblasts. These findings indicate 17beta-E(2) modulates osteoblast function by NO-dependent mechanisms mediated via the eNOS isoform.
O'Shaughnessy
M C
MC
Department of Histochemistry, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, United Kingdom.
Polak
J M
JM
Afzal
F
F
Hukkanen
M V
MV
Huang
P
P
MacIntyre
I
I
Buttery
L D
LD
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D051381:Rats
D009569:Nitric Oxide; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C496316:Nos3 protein, rat