Isopropanolic extract of black cohosh stimulates osteoprotegerin production by human osteoblasts
Isopropanolic extract of black cohosh stimulates osteoprotegerin production by human osteoblasts
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DOI：
10.1359/jbmr.050716
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发表时间：
2005-11-01
影响因子：
6.2
通讯作者：
Hofbauer, LC
中科院分区：
文献类型：
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作者：
Viereck, V;Gründker, C;Hofbauer, LC
引言：尽管雌激素替代疗法对骨骼有积极作用，但由于其增加心血管、血栓栓塞和乳腺癌的风险，已不再推荐作为预防和治疗绝经后骨质疏松症的一线疗法。最近，草药疗法，如从黑升麻根茎中提取的异丙醇提取物（iCR），作为治疗更年期症状的一种替代方法，正引起人们的兴趣。尽管在大鼠身上进行的动物研究表明其对骨骼有积极的影响，但其对骨细胞的作用机制尚不清楚。RANKL对破骨细胞的形成和激活至关重要，而骨保护素（OPG）可以中和RANKL。材料和方法：在本研究中，我们通过半定量RT-PCR评估了iCR对人成骨细胞（hOBs） OPG和RANKL mRNA稳态水平的影响，并通过ELISA系统评估了iCR对蛋白质产生的影响。结果:无血清条件下,用iCR治疗功能增加mRNA水平和蛋白质的分泌滚铣刀通过2 -三倍剂量依赖性的方式,用最大的效果在一个10(6)倍稀释的iCR (p < 0.001)后24 - 48 h。时间进程实验表明刺激效应的iCR成骨细胞的功能蛋白质分泌3 - 5倍(p < 0.001),早在12 h,而RANKL表达很低,不存在被iCR调制。值得注意的是，iCR对OPG产生的刺激作用被纯雌激素受体拮抗剂ICI 182780所消除。此外，iCR增强了两种成骨细胞分化标志物，骨特异性碱性磷酸酶活性和骨钙素表达，分别高达4倍和3倍（p < 0.001）。结论：我们的数据表明，iCR促进了正常人成骨细胞的分化，并增加了opg与rankl的比值。这些影响可能有助于黑升麻对骨骼的积极影响。
Introduction: Despite its positive effects on the skeleton, estrogen replacement therapy is no longer recommended as first-line therapy for the prevention and treatment of postmenopausal osteoporosis because it increases cardiovascular, thromboembolic, and breast cancer risk. Recently, herbal therapeutics such as an isopropanolic extract (iCR) from the rhizomes of Cimicifuga (=Actaea) racemosa (black cohosh) are gaining interest as an alternative in the treatment of menopausal symptoms. Whereas animal studies in rats suggest positive skeletal effects, the mechanism of its actions on bone cells remain unclear. RANKL is essential for osteoclast formation and activation, while osteoprotegerin (OPG) neutralizes RANKL.Materials and Methods: In this study, we assessed the effects of iCR on OPG and RANKL mRNA steady-state levels by semiquantitative RT-PCR and on protein production by an ELISA system in human osteoblasts (hOBs).Results: Under serum-free conditions, treatment with iCR increased OPG mRNA levels and protein secretion of hOBs by 2- to 3-fold in a dose-dependent manner, with a maximum effect at a 10(6)-fold dilution of iCR (p < 0.001) after 24-48 h. Time-course experiments indicated a stimulatory effect of iCR on osteoblastic OPG protein secretion by 3- to 5-fold (p < 0.001) as early as 12 h, whereas RANKL expression was very low and was not found to be modulated by iCR. Of note, the stimulatory effect of iCR on OPG production was abrogated by the pure estrogen receptor antagonist ICI 182,780. Moreover, iCR enhanced two osteoblastic differentiation markers, bone-specific alkaline phosphatase activity and osteocalcin expression, by up to 4- and 3-fold, respectively (p < 0.001).Conclusions: Our data suggest that iCR enhances differentiation and increases the OPG-to-RANKL ratio of normal human osteoblasts. These effects may contribute to the positive skeletal effects of black cohosh.