Cited by 638Bone Metabolism and DiseasesBone health and osteoporosis researchAdipokines, Inflammation, and Metabolic Diseases

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Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

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Kim, Hyeonwoo, Wrann, Christiane D., Jedrychowski, Mark, Vidoni, Sara, Kitase, Yukiko, Nagano, Kenichi, Zhou, Chenhe, Chou, Joshua, Parkman, Virginia-Jeni A., Novick, Scott J., Strutzenberg, Timothy S., Pascal, Bruce D., Le, Phuong T., Brooks, Daniel J., Roche, Alexander M., Gerber, Kaitlyn K., Mattheis, Laura, Chen, Wenjing, Tu, Hua, Bouxsein, Mary L., Griffin, Patrick R., Baron, Roland, Rosen, Clifford J., Bonewald, Lynda F., Spiegelman, Bruce M.·2018·Cell

DOI 10.1016/j.cell.2018.10.025PMC PMC6707723

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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.

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Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction
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New and Old Osteocytic Cell Lines and 3D Models
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Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
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Recombinant irisin enhances the extracellular matrix formation, remodeling potential, and differentiation of human periodontal ligament cells cultured in 3D
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Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells
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“Lean FNDC5-deficient mice did not show obvious metabolic defects in our previous studies 14 .”
Self-citation
Iditarod , a Drosophila homolog of the Irisin precursor FNDC5 , is critical for exercise performance and cardiac autophagy
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Novel insights into osteocyte and inter-organ/tissue crosstalk
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Applying exercise-mimetic engineered skeletal muscle model to interrogate the adaptive response of irisin to mechanical force
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Irisin improves delayed bone repair in diabetic female mice
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Dietary Intervention, When Not Associated With Exercise, Upregulates Irisin/FNDC5 While Reducing Visceral Adiposity Markers in Obese Rats
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Irisin effects on bone: systematic review with meta-analysis of preclinical studies and prospects for oral health
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Myokine secretion following moderate-intensity endurance exercise under different environmental temperatures
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Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx
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Carcass composition, meat quality, leg muscle status, and its mRNA expression profile in broilers affected by valgus-varus deformity
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Cognitive Dysfunction and Exercise: From Epigenetic to Genetic Molecular Mechanisms
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Authors: 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., Bouxsein, M. L., Griffin, P. R., Baron, R., Rosen, C. J., Bonewald, L. F., & Spiegelman, B. M.
Affiliations: Harvard University (US)
Indiana University Indianapolis (US)
Scripps Research Institute (US)
Maine Medical Center Research Institute (US)
Beth Israel Deaconess Medical Center (US)
LakePharma (United States) (US)
Corresponding author: Spiegelman, Bruce M.
ORCID: Kim, Hyeonwoo
Wrann, Christiane D.
Vidoni, Sara
Kitase, Yukiko
Nagano, Kenichi
Zhou, Chenhe
Chou, Joshua
Novick, Scott J.
Strutzenberg, Timothy S.
Pascal, Bruce D.
Brooks, Daniel J.
Roche, Alexander M.
Chen, Wenjing
Tu, Hua
Bouxsein, Mary L.
Griffin, Patrick R.
Baron, Roland
Rosen, Clifford J.
Bonewald, Lynda F.
Spiegelman, Bruce M.
Venue: Cell
Publisher: Elsevier BV
Published: 2018-12
Volume: 175
Issue: 7
Pages: 1756-1768.e17
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2018.10.025
PMC: PMC6707723
OpenAlex: W2905310978
Cited by: 638
References: 91
Citations by year: 2026: 66 · 2025: 96 · 2024: 93 · 2023: 83 · 2022: 100 · 2021: 94 · 2020: 59 · 2019: 44 · 2018: 1
FWCI: 17.61
Type: journal article
Language: en
Update notices: erratum (2019-07-11)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
IUScholarWorks (Indiana University) (submittedVersion)
Purdue University Indianapolis (Indiana University) (submittedVersion)
Funders: NIH (4 R01DK54477-19, DK61502, 5T32HL007374-38, K99NS087096, PO1AG039335, NIDDK RC2 092759)
JPB Foundation (6293803)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: irisin, FNDC5, ITGAV, osteocytes, osteolysis, sclerostin, bone remodeling, adipose tissue, physical activity, ovariectomy, bone loss, integrin signaling
MeSH terms: Adipose Tissue, Animals, Female, Fibronectins, Humans, Osteocytes, Osteolysis, Bone Remodeling, Adipocytes, Integrin alphaV, Cell Line, Tumor, Mice, HEK293 Cells

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Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

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