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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis
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Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

机译：FSHβ亚基的封闭抗体可通过抑制骨吸收和刺激骨合成来防止骨质流失

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摘要

Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins 3 y before the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during late perimenopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13-amino-acid-long peptide sequence within the receptor-binding domain of the FSH β-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSH receptor (FSHR)~(―/―) mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans.
机译：雌激素水平低无疑是更年期骨骼变薄的基础。但是，当血清雌激素相对正常时，迅速大量的骨质流失会在最后一次月经期前3年开始。我们已经显示垂体激素FSH的水平在围绝经后期比较高，它直接刺激破骨细胞吸收骨。在这里，我们生成并鉴定了针对FSHβ亚基受体结合域内13个氨基酸长的肽序列的多克隆抗体。我们显示FSH抗体特异性结合FSH，并在体外阻断其对破骨细胞形成的作用。当将FSH抗体注射入卵巢切除小鼠后，不仅通过抑制骨吸收，而且通过刺激骨形成来显着减轻骨质流失，这是我们在本文中报道的FSH尚未表现出来的作用。与FSH受体（FSHR）〜（-/-）小鼠分离的间充质细胞相似，用FSH抗体处理的小鼠分离的间质细胞显示出更高的成骨细胞前体集落数。这表明FSH负调节成骨细胞数量。我们证实该作用是由间充质干细胞上存在的信号有效的FSHRs介导的。总的来说，这些数据提示了FSH阻断剂的未来发展，它是一种将骨形成和骨吸收脱钩的手段，可在人体中发挥治疗作用。

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    Ling-Ling Zhu; Harry Blair; Jay Cao; Tony Yuen; Rauf Latif; Lida Guo; Irina L. Tourkova; Jianhua Li; Terry F. Davies; Li Sun; Zhuan Bian; Clifford Rosen; Alberta Zallone; Maria I. New; Mone Zaidi;

  • 作者单位

    Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029,Wuhan University School of Stomatology,Wuhan, China;

    Departments of Pathology and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261,Pittsburgh VA Medical Center, Pittsburgh,PA 15240;

    Department of Agriculture Human Nutrition Research Center, Fargo, ND 58203;

    Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029;

    Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029;

    Departments of Pathology and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261;

    Departments of Pathology and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261;

    Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029;

    Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029;

    Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029;

    Wuhan University School of Stomatology,Wuhan, China;

    Center for Clinical & Translational Research, Maine Medical Center Research Institute, Scarborough, ME 04074;

    Department of Human Anatomy and Histology, University of Bari Medical School, Bari 70124, Italy;

    Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029;

    Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    osteoporosis; sex steroids; skeletal anabolic; gonadotropin;

    机译：骨质疏松症性类固醇;骨骼合成代谢促性腺激素;

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