Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Kim, H; Wrann, CD; Jedrychowski, M; Vidoni, S; Kitase, Y; Nagano, K; Zhou, C; Chou, J; Parkman, VJA; Novick, SJ; Strutzenberg, TS; Pascal, BD; Le, PT; Brooks, DJ; Roche, AM; Gerber, KK; Mattheis, L; Chen, W; Tu, H; Bouxsein, ML; Griffin, PR; Baron, R; Rosen, CJ; Bonewald, LF; Spiegelman, BM

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Kim, H Wrann, CD Jedrychowski, M Vidoni, S Kitase, Y Nagano, K Zhou, C Chou, J

Parkman, VJA Novick, SJ Strutzenberg, TS Pascal, BD Le, PT Brooks, DJ Roche, AM Gerber, KK Mattheis, L Chen, W Tu, H Bouxsein, ML Griffin, PR Baron, R Rosen, CJ Bonewald, LF Spiegelman, BM

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Publication Type:: Journal Article
Citation:: Cell, 2018, 175 (7), pp. 1756 - 1768.e17
Issue Date:: 2018-12-13

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Field	Value	Language
dc.contributor.author	Kim, H	en_US
dc.contributor.author	Wrann, CD	en_US
dc.contributor.author	Jedrychowski, M	en_US
dc.contributor.author	Vidoni, S	en_US
dc.contributor.author	Kitase, Y	en_US
dc.contributor.author	Nagano, K	en_US
dc.contributor.author	Zhou, C	en_US
dc.contributor.author	Chou, J https://orcid.org/0000-0002-7472-8016	en_US
dc.contributor.author	Parkman, VJA	en_US
dc.contributor.author	Novick, SJ	en_US
dc.contributor.author	Strutzenberg, TS	en_US
dc.contributor.author	Pascal, BD	en_US
dc.contributor.author	Le, PT	en_US
dc.contributor.author	Brooks, DJ	en_US
dc.contributor.author	Roche, AM	en_US
dc.contributor.author	Gerber, KK	en_US
dc.contributor.author	Mattheis, L	en_US
dc.contributor.author	Chen, W	en_US
dc.contributor.author	Tu, H	en_US
dc.contributor.author	Bouxsein, ML	en_US
dc.contributor.author	Griffin, PR	en_US
dc.contributor.author	Baron, R	en_US
dc.contributor.author	Rosen, CJ	en_US
dc.contributor.author	Bonewald, LF	en_US
dc.contributor.author	Spiegelman, BM	en_US
dc.date.available	2018-10-07	en_US
dc.date.issued	2018-12-13	en_US
dc.identifier.citation	Cell, 2018, 175 (7), pp. 1756 - 1768.e17	en_US
dc.identifier.issn	0092-8674	en_US
dc.identifier.uri	http://hdl.handle.net/10453/130631
dc.description.abstract	© 2018 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.	en_US
dc.relation.ispartof	Cell	en_US
dc.relation.isbasedon	10.1016/j.cell.2018.10.025	en_US
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Developmental Biology	en_US
dc.subject.mesh	Adipose Tissue	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Adipocytes	en_US
dc.subject.mesh	Osteocytes	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Osteolysis	en_US
dc.subject.mesh	Fibronectins	en_US
dc.subject.mesh	Integrin alphaV	en_US
dc.subject.mesh	Bone Remodeling	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	HEK293 Cells	en_US
dc.title	Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	175	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1106 Human Movement and Sports Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access	*
pubs.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	175	en_US

Abstract:

© 2018 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/130631