title: Nitric oxide mediates 17beta-estradiol-stimulated human and rodent osteoblast proliferation and differentiation.
abstract: 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.
authors.affiliation: Department of Histochemistry, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, United Kingdom.
authors.forename: M C
authors.initials: MC
authors.lastname: O'Shaughnessy
authors.forename: J M
authors.initials: JM
authors.lastname: Polak
authors.forename: F
authors.initials: F
authors.lastname: Afzal
authors.forename: M V
authors.initials: MV
authors.lastname: Hukkanen
authors.forename: P
authors.initials: P
authors.lastname: Huang
authors.forename: I
authors.initials: I
authors.lastname: MacIntyre
authors.forename: L D
authors.initials: LD
authors.lastname: Buttery
mesh_terms: 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
chemical_list: 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