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Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors
Open accessAbstract
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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Comparative Protein Modelling by Satisfaction of Spatial Restraints
Šali, A., & Blundell, T. L. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1626 · Cited by 12,977 · cited 1×
“The models for integrin β5 and irisin were generated using Modeller (Sali and Blundell, 1993) based on a model of Fibronectin-αV/β3 (PDB 4MMX).”
Mass Spectrometric Sequencing of Proteins from Silver-Stained Polyacrylamide Gels
Shevchenko, A., Wilm, M. S., Vorm, O., & Mann, M. (1996) · Analytical Chemistry · doi:10.1021/ac950914h · Cited by 8,996
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., et al. (2012) · Nature · doi:10.1038/nature10777 · Cited by 4,810
Self-citationSkyline: an open source document editor for creating and analyzing targeted proteomics experiments
MacLean, B., Tomazela, D. M., Shulman, N., Chambers, M., Finney, G. L., Frewen, B., Kern, R., Tabb, D. L., Liebler, D. C., & MacCoss, M. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq054 · Cited by 4,697
Rappsilber, J., Mann, M., & Ishihama, Y. (2007) · Nature Protocols · doi:10.1038/nprot.2007.261 · Cited by 4,641
Guidelines for assessment of bone microstructure in rodents using micro–computed tomography
Bouxsein, M., Boyd, S. K., Christiansen, B., Guldberg, R. E., Jepsen, K. J., & Müller, R. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.141 · Cited by 4,461 · cited 1×
“Image acquisition and analysis protocols adhered to the JBMR guidelines for the assessment of rodent bones by μCT (Bouxsein et al., 2010).”
Self-citationElias, J. E., & Gygi, S. P. (2007) · Nature Methods · doi:10.1038/nmeth1019 · Cited by 3,925 · cited 3×
“A MS2 spectra assignment false discovery rate (FDR) of less than 1% was achieved by applying the target- decoy database search strategy (Elias and Gygi, 2007).”
InfluentialGiancotti, F. G., & Ruoslahti, E. (1999) · Science · doi:10.1126/science.285.5430.1028 · Cited by 3,869 · cited 8×
“We observed that anti-integrin αV/ β5 completely blocked the irisin-mediated phosphorylation of FAK, Zyxin and CREB, while control Igg or the anti-integrin αV/β3 did not block signaling (Figure 5C).”
InfluentialMuscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · cited 1×
“Physical activity doesn’t only target osteocytes but also stimulates the production of several hormone-like molecules from skeletal muscle termed “myokines” (Pedersen and Febbraio, 2012).”
Dempster, D. W., Compston, J. E., Drezner, M. K., Glorieux, F. H., Kanis, J. A., Malluche, H., Meunier, P. J., Ott, S. M., Recker, R. R., & Parfitt, A. M. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1805 · Cited by 2,543
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Islam, M. R., Valaris, S., Young, M. F., Haley, E. B., Luo, R., Bond, S. F., Mazuera, S., Kitchen, R. R., Caldarone, B. J., Bettio, L. E. B., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00438-z · Cited by 403
Self-citationThe Regulation of Bone Metabolism and Disorders by Wnt Signaling
Maeda, K., Kobayashi, Y., Koide, M., Uehara, S., Okamoto, M., Ishihara, A., Kayama, T., Saito, M., & Marumo, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225525 · Cited by 360
Metadata
- 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)
- 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
- 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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