Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.
Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.
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卵泡刺激激素通过刺激破骨细胞分化增加绝经后骨质疏松症的风险
DOI：
10.1371/journal.pone.0134986
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Wang J;Zhang W;Yu C;Zhang X;Zhang H;Guan Q;Zhao J;Xu J
目的观察绝经后妇女血清卵泡刺激素(FSH)和骨密度(BMD)的变化，探讨FSH与绝经后骨质疏松症的关系，以及FSH对RAW264.7细胞破骨细胞分化的影响。方法对248例骨代谢正常的绝经后妇女进行分析。用放射免疫分析法(RIA)检测血清FSH、黄体生成素(LH)和雌二醇(E_2)。采用双能X线骨密度仪测量前臂骨密度。分析血清FSH、LH、E_2的增龄性变化。此外，对一组患有骨质疏松症的绝经后妇女和一组对照组的血清FSH浓度进行了比较。用核因子kappa B受体激活剂(RANKL)体外诱导RAW264.7细胞破骨细胞，用0、5、10、20 ng/mlFSH处理破骨细胞。破骨细胞成熟后，用抗酒石酸酸性磷酸酶(TRAP)染色鉴定破骨细胞，用实时定量聚合酶链式反应(Real-time PCR)检测与破骨细胞表型和功能相关的基因如核因子受体激活剂RANK(Rank)、TRAP、基质金属蛋白酶9(MMP9)、组织蛋白酶K(Cathepsin K)在不同组别中的表达水平。结果1.绝经后骨质疏松症患者血清FSH水平较对照组显著升高。2.RANKL体外诱导RAW264.7细胞向成熟破骨细胞分化。3.FSH以剂量依赖的方式增加破骨细胞表型和功能相关基因Rank、Trap、MMP一9、Cathepsin K的mRNA表达。结论FSH的循环浓度可能在绝经后妇女加速骨丢失中起重要作用。FSH在体外可促进破骨细胞的形成。
Objective The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells. Methods We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction). Results 1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner. Conclusions The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.