4.8 Article

Autoregulation of Osteocyte Sema3A Orchestrates Estrogen Action and Counteracts Bone Aging

期刊

CELL METABOLISM
卷 29, 期 3, 页码 627-+

出版社

CELL PRESS
DOI: 10.1016/j.cmet.2018.12.021

关键词

-

资金

  1. Japan Science and Technology Agency [JPMJPR13MC]
  2. AMED-CREST, AMED [JP17gm0810003]
  3. Japan Society for the Promotion of Science (JSPS)
  4. Mochida Memorial Foundation
  5. Terumo Foundation
  6. Life Science Foundation of Japan
  7. Takeda Science Foundation
  8. Uehara Memorial Foundation
  9. Ichiro Kanehara Foundation
  10. Kanazawa Medical Research Foundation
  11. Naito Foundation
  12. Nakatomi Foundation
  13. Astellas Foundation for Research on Metabolic Disorders
  14. Sumitomo Foundation
  15. Asahi Glass Foundation
  16. Mitsui Life Social Welfare Foundation
  17. Daiichi Sankyo Foundation
  18. ONO Medical Research Foundation
  19. Secom Science and Technology Foundation

向作者/读者索取更多资源

Osteocyte survival is key to bone homeostasis and is perturbed in menopause and aging. However, it remains unknown how osteocyte-mediated maintenance of the skeleton is regulated by the osteoprotective factor semaphorin 3A (Sema3A), a secreted protein that is known to reduce bone resorption and enhance bone formation. Here, we show that estrogen induces osteocyte expression of Sema3A, which acts on its receptor on osteocytes to promote their survival and maintain bone homeostasis. Postnatal global and conditional deletion of Sema3a in osteoblastic cells resulted in a severe osteoporotic phenotype marked by fewer osteocytes. This phenotype was recapitulated by osteocyte-specific deficiency of either Sema3A or its receptor component neuropilin-1 (Nrp1). A stimulator of soluble guanylate cyclase-cGMP signaling mimicked Sema3A action and ameliorated bone loss after ovariectomy. We further show that serum levels of SEMA3A decreased with age or after menopause in humans. Thus, we provide a mechanistic insight into the estrogen action and a promising therapeutic approach to protect against bone-related aging.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据