Sun Li, Peng Yuanzhen, Sharrow Allison C, Iqbal Jameel, Zhang Zhiyuan, Papachristou Dionysios J, Zaidi Samir, Zhu Ling-Ling, Yaroslavskiy Beatrice B, Zhou Hang, Zallone Alberta, Sairam M Ram, Kumar T Rajendra, Bo Wei, Braun Jonathan, Cardoso-Landa Luis, Schaffler Mitchell B, Moonga Baljit S, Blair Harry C, Zaidi Mone
Mount Sinai Bone Program, Department of Medicine and Department of Orthopedics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Cell. 2006 Apr 21;125(2):247-60. doi: 10.1016/j.cell.2006.01.051.
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 FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass is increased and osteoclastic resorption is decreased in haploinsufficient FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent. Osteoclasts and their precursors possess G(i2alpha)-coupled FSHRs that activate MEK/Erk, NF-kappaB, and Akt to result in enhanced osteoclast formation and function. We suggest that high circulating FSH causes hypogonadal bone loss.
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完全是由雌激素水平下降所致。尽管促卵泡激素（FSH）水平同时急剧上升，但FSH对骨骼的直接作用从未被探究过。我们发现，性腺功能减退导致的骨质流失需要FSH。尽管存在严重的性腺功能减退，但促卵泡激素β（FSHβ）基因敲除小鼠和促卵泡激素受体（FSHR）基因敲除小鼠均未出现骨质流失。在卵巢功能正常的FSHβ基因单倍不足（FSHβ+/-）小鼠中，骨量增加，破骨细胞吸收减少，这表明FSH对骨骼的作用不依赖于雌激素。破骨细胞及其前体细胞拥有与G(i2α)偶联的FSHR，可激活丝裂原活化蛋白激酶/细胞外信号调节激酶（MEK/Erk）、核因子κB（NF-κB）和蛋白激酶B（Akt），从而增强破骨细胞的形成和功能。我们认为，循环中FSH水平升高会导致性腺功能减退性骨质流失。
