O'Shaughnessy M C, Polak J M, Afzal F, Hukkanen M V, Huang P, MacIntyre I, Buttery L D
Department of Histochemistry, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, United Kingdom.
Biochem Biophys Res Commun. 2000 Nov 2;277(3):604-10. doi: 10.1006/bbrc.2000.3714.
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.
雌二醇可刺激成骨细胞活性。成骨细胞功能被认为受一氧化氮（NO）调节。我们推测17β-雌二醇（17β-E₂）对成骨细胞活性的影响是由NO介导的。使用从人松质骨、大鼠颅骨、内皮型一氧化氮合酶（eNOS）基因缺陷小鼠及其野生型对照分离出的成骨细胞对这一假设进行了验证。我们的结果表明，17β-E₂ 剂量依赖性地刺激原代人、大鼠和野生型成骨细胞的增殖和分化。NOS活性抑制剂N(G)-单甲基-L-精氨酸（10⁻³ M）的存在，分别阻断了17β-E₂（10⁻⁷ M）诱导的野生型、人和大鼠成骨细胞的胸苷掺入增加（P < 0.01）、碱性磷酸酶活性增加（P < 0.01）和骨结节形成增加（P < 0.01）。此外，17β-E₂ 对eNOS基因缺陷的成骨细胞未诱导出反应。17β-E₂ 还增加了大鼠成骨细胞中总eNOS酶的表达。这些发现表明，17β-E₂ 通过由eNOS亚型介导的NO依赖性机制调节成骨细胞功能。
