Icariin protects against bone loss induced by oestrogen deficiency and activates oestrogen receptor-dependent osteoblastic functions in UMR 106 cells
Icariin protects against bone loss induced by oestrogen deficiency and activates oestrogen receptor-dependent osteoblastic functions in UMR 106 cells
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DOI：
10.1111/j.1476-5381.2009.00593.x
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发表时间：
2010-02-01
影响因子：
7.3
通讯作者：
Wong, Man-Sau
中科院分区：
文献类型：
--
作者：
Mok, Sao-Keng;Chen, Wen-Fang;Wong, Man-Sau
背景与目的：淫羊藿苷可能是治疗骨质疏松症常用中药淫羊藿的有效成分。本研究旨在阐明淫羊藿苷在体内预防卵巢切除术（OVX）后骨丢失和在vitro刺激成骨细胞功能的机制。实验方法：用载体、17 β-雌二醇或淫羊藿苷治疗卵巢切除或假手术的C57 BL/6小鼠6周。采用外周CT测量股骨远端的总骨密度、骨小梁骨密度（BMD）和极应力应变指数。RT-PCR检测胫骨组织中OPG和RANKL的mRNA表达。在UMR 106细胞中研究了雌激素受体（ER）拮抗剂ICI 182，780与淫羊藿苷的相互作用。结果：淫羊藿苷能抑制OVX后大鼠股骨远端骨量和骨强度的丢失，并能增加OPG/RANKL的mRNA表达。淫羊藿苷可增加ER依赖的UMR 106细胞增殖、碱性磷酸酶（ALP）活性、OPG基因表达和OPG/RANKL比值。淫羊藿苷不通过ER α或ER β介导的途径激活UMR 106细胞中的ER荧光素酶活性，但它确实增加了ER α在Ser 118的磷酸化。结论和意义：我们的研究结果表明，淫羊藿苷可能通过激活ER以配体非依赖性的方式发挥骨合成代谢作用。它能够防止卵巢切除引起的骨丢失，而不诱导子宫肥大效应，支持其作为管理绝经后骨质疏松症的替代方案。
Background and purpose:Icariin may be the active ingredient in Herba Epimedii, a Chinese herb commonly used for treatment of osteoporosis. The present study aims to delineate the mechanism(s) by which icariin prevents bone loss after ovariectomy (OVX) in vivo and stimulates osteoblastic functions in vitro.Experimental approach:Ovariectomized or sham-operated C57BL/6 mice were treated with vehicle, 17 beta-oestradiol or icariin for 6 weeks. Total and trabecular bome mineral density (BMD) as well as polar stress-strain index of distal femur were measured by peripheral computed tomography. The mRNA expressions of OPG and RANKL in tibia were studied by RT-PCR. Interactions between the oestrogen receptor (ER) antagonist ICI182,780 and icariin were studied in UMR 106 cells. The functional transactivation of ER alpha and ER beta as well as ER alpha phosphorylation by icariin were also assessed.Key results:Icariin suppressed the loss of bone mass and strength in distal femur and increased the mRNA expression ratio of OPG/RANKL in tibia, following OVX. Icariin increased ER-dependent cell proliferation, alkaline phosphatase (ALP) activity, gene expression of OPG and the OPG/RANKL ratio in UMR 106 cells. Icariin did not activate ERE-luciferase activity in UMR 106 cells, via the ER alpha or the ER beta-mediated pathway, but it did increase ER alpha phosphorylation at Ser118.Conclusions and implications:Our results indicate that icariin exerts anabolic effects in bone possibly by activating ER in a ligand-independent manner. Its ability to prevent OVX-induced bone loss without inducing uterotrophic effects supports its use as an alternative regimen for management of postmenopausal osteoporosis.