Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors.

Document Type

Article

Publication Date

12-13-2018

Institution/Department

Maine Medical Center Research Institute

Journal Title

Cell

MeSH Headings

Adipocytes, Adipose Tissue, Animals, Bone Remodeling, Cell Line, Tumor, Female, Fibronectins, HEK293 Cells, Humans, Integrin alphaV, Mice, Osteocytes, Osteolysis

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.

ISSN

1097-4172

First Page

1756

Last Page

1768

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