FSH directly regulates bone mass
FSH directly regulates bone mass
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DOI：
10.1016/j.cell.2006.01.051
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发表时间：
2006-04-21
期刊：
影响因子：
64.5
通讯作者：
Zaidi, M
中科院分区：
文献类型：
--
作者：
Sun, L;Peng, Y;Zaidi, M
绝经后骨质疏松症是一个全球性的公共卫生问题，几十年来一直被认为是雌激素水平下降的唯一原因。尽管FSH水平同时急剧上升，但FSH对骨骼的直接影响从未被探索过。我们发现促卵泡刺激素是性腺功能低下的骨质流失所必需的。FSH β和FSH受体（FSHR）缺失的小鼠尽管有严重的性腺功能减退，但都没有骨质流失。卵巢功能正常、单倍素充足的FSHD+/-小鼠骨量增加，破骨细胞吸收减少，提示FSH对骨骼的作用不依赖于雌激素。破骨细胞及其前体具有G（i2 α）偶联FSHRs，可激活MEK/Erk、nf - κ B和Akt，从而增强破骨细胞的形成和功能。我们认为高循环FSH会导致性腺功能低下的骨质流失。
Postmenopausal osteoporosis, a global public health problem, has for decades been attributed solely to declining estrogen levels. Although FSH levels rise sharply in parallel, a direct effect of FSH on the skeleton has never been explored. We show that FSH is required for hypogonadal bone loss. Neither FSH beta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass is increased and osteoclastic resorption is decreased in haploin-sufficient FSHD+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent. Osteoclasts and their precursors possess G(i2 alpha)-COupled FSHRs that activate MEK/Erk, NF-kappa B, and Akt to result in enhanced osteoclast formation and function. We suggest that high circulating FSH causes hypogonadal bone loss.