Nitric oxide mediates 17 beta-estradiol-stimulated human and rodent osteoblast proliferation and differentiation

Oestradiol can stimulate osteoblast activity. Osteoblast function is though t to be regulated by nitric oxide (NO), We hypothesised that the effect of 17 beta -oestradiol (17 beta -E-2) on osteoblast activity is mediated by NO . This hypothesis was tested using osteoblasts isolated from human trabecul ar bone, calvariae of rats, endothelial NO synthase (eNOS) gene-deficient m ice, and their wild-type counterparts. Our results show that 17 beta -E-2 d ose-dependently stimulated proliferation and differentiation of primary hum an, rat and wild-type osteoblasts. The presence of N-G-monomethyl-L-arginin e (10(-3) M), an inhibitor of NOS activity, blocked the 17 beta -E-2-(10(-7 ) M)-induced increases in thymidine incorporation (P < 0.01), alkaline phos phatase activity (P < 0.01) and bone nodule formation (P < 0.01) of wild-ty pe, human and rat osteoblasts, respectively. Moreover, 17<beta>-E-2 did not induce a response in eNOS gene-deficient osteoblasts. 17 beta -E-2 also in creased total eNOS enzyme expression in rat osteoblasts. These findings ind icate 17 beta -E-2 modulates osteoblast function by NO-dependent mechanisms mediated via the eNOS isoform, (C) 2000 Academic Press.