Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Hyeonwoo Kim, Christiane D. Wrann, Mark Jedrychowski, Sara Vidoni, Yukiko Kitase, Kenichi Nagano, Chenhe Zhou, Joshua Chou, Virginia Jeni A. Parkman, Scott J. Novick, Timothy S. Strutzenberg, Bruce D. Pascal, Phuong T. Le, Daniel J. Brooks, Alexander M. Roche, Kaitlyn K. Gerber, Laura Mattheis, Wenjing Chen, Hua Tu, Mary L. BouxseinPatrick R. Griffin, Roland Baron, Clifford J. Rosen, Lynda F. Bonewald, Bruce M. Spiegelman

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Irisin is secreted by muscle, increases with exercise, and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear, and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins, and biophysical studies identify interacting surfaces between irisin and αV/β5 integrin. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5 (or irisin) completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling. Identification of the irisin receptor should greatly facilitate our understanding of irisin's function in exercise and human health. Irisin, through its integrin receptor, promotes skeletal remodeling with implications for stemming bone loss.

Original languageEnglish (US)
Pages (from-to)1756-1768.e17
JournalCell
Volume175
Issue number7
DOIs
StatePublished - Dec 13 2018

Keywords

  • Irisin receptor
  • bone resorption
  • integrin αV
  • irisin
  • osteocyte
  • sclerostin
  • subcutaneous (inguinal) adipose tissues
  • ucp1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kim, H., Wrann, C. D., Jedrychowski, M., Vidoni, S., Kitase, Y., Nagano, K., Zhou, C., Chou, J., Parkman, V. J. A., Novick, S. J., Strutzenberg, T. S., Pascal, B. D., Le, P. T., Brooks, D. J., Roche, A. M., Gerber, K. K., Mattheis, L., Chen, W., Tu, H., ... Spiegelman, B. M. (2018). Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors. Cell, 175(7), 1756-1768.e17. https://doi.org/10.1016/j.cell.2018.10.025