Li Sun,
Yuanzhen Peng,
Allison C Sharrow,
Jameel Iqbal,
Zhiyuan Zhang,
Dionysios J Papachristou,
Samir Zaidi,
Ling-Ling Zhu,
Beatrice B Yaroslavskiy,
Hang Zhou,
Alberta Zallone,
M Ram Sairam,
T Rajendra Kumar,
Wei Bo, Jonathan Braun,
Luis Cardoso-Landa,
Mitchell B Schaffler,
Baljit S Moonga,
Harry C Blair,
Mone Zaidi
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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.
Cell 05/2006; 125(2):247-60. · 32.40 Impact Factor
