FSH directly regulates bone mass |
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Authors: | 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 |
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Affiliation: | Mount Sinai Bone Program, Department of Medicine and Department of Orthopedics, Mount Sinai School of Medicine, New York, NY 10029, USA. |
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Abstract: | 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. |
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