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

The DOI matches its Crossref record; 90 of the 91 references it cites were found in a registry or an index.

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Open access

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

Open this paper in CoChat — free account Open PDF

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.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2018.10.025

Cites

90 of 90 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

The text we found for this paper looks like another document, so its claims and self-check weren’t run. The registry and citation checks still apply.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The text we found for this paper looks like another document, so the self-check wasn’t run.

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-citation
Skyline: 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
Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips
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-citation
Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry
Elias, 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).”
Influential
Integrin signaling
Giancotti, 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).”
Influential
Muscles, 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).”
Standardized nomenclature, symbols, and units for bone histomorphometry: A 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee
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

Flagged first, then by citations

Show all 91 references

1 of the 91 references couldn’t be matched to a known paper.

Sorted by citations

Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927
Challenges and advances in clinical applications of mesenchymal stromal cells
Zhou, T., Yuan, Z., Weng, J., Pei, D., Du, X., He, C., & Lai, P. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01037-x · Cited by 712
The Osteocyte: New Insights
Robling, A. G., & Bonewald, L. F. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021119-034332 · Cited by 539
Exercise hormone irisin is a critical regulator of cognitive function
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-citation
The 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
Irisin: A Hope in Understanding and Managing Obesity and Metabolic Syndrome
Arhire, L. I., Mihalache, L., & Covașă, M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00524 · Cited by 317
CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling
Oguri, Y., Shinoda, K., Kim, H., Alba, D., Bolus, W. R., Wang, Q., Brown, Z. D., Pradhan, R., Tajima, K., Yoneshiro, T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.021 · Cited by 285
Self-citation
Myokines: The endocrine coupling of skeletal muscle and bone
Gomarasca, M., Banfi, G., & Lombardi, G. (2019) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.010 · Cited by 283
Sarcopenia, osteoporosis and frailty
Gielen, E., Dupont, J., Dejaeger, M., & Laurent, M. R. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155638 · Cited by 282
Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation
Ren, Y., Zhao, H., Yin, C., Lan, X., Wu, L., Du, X., Griffiths, H. R., & Gao, D. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.873699 · Cited by 276
Progress and Challenges in the Biology of FNDC5 and Irisin
Maak, S., Norheim, F., Drevon, C. A., & Erickson, H. P. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab003 · Cited by 247
Use it or lose it to age: A review of bone and muscle communication
Bonewald, L. F. (2018) · Bone · doi:10.1016/j.bone.2018.11.002 · Cited by 236
Self-citation
Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin αVβ5/AMPK signaling pathway after intracerebral hemorrhage in mice
Wang, Y., Tian, M., Tan, J., Pei, X., Lu, C., Xin, Y., Deng, S., Zhao, F., Gao, Y., & Gong, Y. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02438-6 · Cited by 232
Muscle-derived miR-34a increases with age in circulating extracellular vesicles and induces senescence of bone marrow stem cells
Fulzele, S., Mendhe, B., Khayrullin, A., Johnson, M. H., Kaiser, H., Liu, Y., Isales, C. M., & Hamrick, M. W. (2019) · Aging · doi:10.18632/aging.101874 · Cited by 220
FNDC5/Irisin: Physiology and Pathophysiology
Waseem, R., Shamsi, A., Mohammad, T., Hassan, M. I., Kazim, S. N., Chaudhary, A. A., Rudayni, H. A., Al-Zharani, M., Ahmad, F., & Islam, A. (2022) · Molecules · doi:10.3390/molecules27031118 · Cited by 180
New insights into the cellular activities of Fndc5/Irisin and its signaling pathways
Rabiee, F., Lachinani, L., Ghaedi, S., Nasr‐Esfahani, M. H., Megraw, T. L., & Ghaedi, K. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00413-3 · Cited by 188
Role of irisin in physiology and pathology
Liu, S., Cui, F., Ning, K., Wang, Z., Fu, P., Wang, D., & Xu, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.962968 · Cited by 186
Irisin Mitigates Oxidative Stress, Chondrocyte Dysfunction and Osteoarthritis Development through Regulating Mitochondrial Integrity and Autophagy
Wang, F., Kuo, C.-W., Ko, J., Chen, Y., Wang, S., Ke, H.-J., Kuo, P.-C., Lee, C.-H., Wu, J., Lu, W., et al. (2020) · Antioxidants · doi:10.3390/antiox9090810 · Cited by 173
Molecular mechanisms of exercise contributing to tissue regeneration
Chen, J., Zhou, R. J., Ye, F., & Cheng, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01233-2 · Cited by 185
Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis
Li, G., Zhang, L., Wang, D., AIQudsy, L., Jiang, J. X., Xu, H., & Shang, P. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28946 · Cited by 166
Irisin as a Multifunctional Protein: Implications for Health and Certain Diseases
Korta, P., Pocheć, E., & Mazur-Biały, A. I. (2019) · Medicina · doi:10.3390/medicina55080485 · Cited by 169
Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction
Guo, M., Yao, J., Li, J., Zhang, J., Wang, D., Zuo, H., Zhang, Y., Xu, B., Zhong, Y., Shen, F., et al. (2022) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13141 · Cited by 172
Targeting strategies for bone diseases: signaling pathways and clinical studies
Xu, H., Wang, W., Liu, X., Huang, W. H., Chen, Z., Xu, Y., Yang, H., Bai, J., & Geng, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01467-8 · Cited by 177
Metabolic communication during exercise
Murphy, R. M., Watt, M. J., & Febbraio, M. A. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0258-x · Cited by 162
Postmenopausal osteoporosis coexisting with sarcopenia: the role and mechanisms of estrogen
Lu, L., & Tian, L. (2023) · Journal of Endocrinology · doi:10.1530/joe-23-0116 · Cited by 175
Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases
Ru, J., & Wang, Y.-F. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03059-8 · Cited by 159
Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice
Wei, S., Bi, J., Yang, L., Zhang, J., Wan, Y., Chen, X., Wang, Y., Wu, Z., Lv, Y., & Wu, R. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.173 · Cited by 146
Myokines and Resistance Training: A Narrative Review
Zunner, B. E. M., Wachsmuth, N. B., Eckstein, M. L., Scherl, L., Schierbauer, J., Haupt, S., Stumpf, C., Reusch, L., & Moser, O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073501 · Cited by 146
A role for FNDC5/Irisin in the beneficial effects of exercise on the brain and in neurodegenerative diseases
Young, M. F., Valaris, S., & Wrann, C. D. (2019) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2019.02.007 · Cited by 143
Self-citation
Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin
Farshbaf, M. J., & Alviña, K. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.649929 · Cited by 150
FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective
Pignataro, P., Dicarlo, M., Zerlotin, R., Zecca, C., Dell’Abate, M. T., Buccoliero, C., Logroscino, G., Colucci, S. C., & Grano, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041605 · Cited by 137
Irisin reduces amyloid-β by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling
Kim, E., Kim, H., Jedrychowski, M. P., Bakiasi, G., Park, J., Kruskop, J. M., Choi, Y., Kwak, S. S., Quinti, L., Kim, D. Y., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.08.012 · Cited by 141
Self-citation
Amelioration of pathologic α-synuclein-induced Parkinson’s disease by irisin
Kam, T.-I., Park, H., Chou, S.-C., Van Vranken, J. G., Mittenbühler, M. J., Kim, H., A, M., Choi, Y. R., Biswas, D., Wang, J., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2204835119 · Cited by 125
Self-citation
Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance
Balakrishnan, R., & Thurmond, D. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094636 · Cited by 143
Irisin Prevents Disuse-Induced Osteocyte Apoptosis
Storlino, G., Colaianni, G., Sanesi, L., Lippo, L., Brunetti, G., Errede, M., Colucci, S. C., Passeri, G., & Grano, M. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3944 · Cited by 125
Bone and Muscle Crosstalk in Aging
He, C., He, W., Hou, J., Chen, K., Huang, M., Yang, M., Luo, X., & Li, C. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.585644 · Cited by 129
Protective actions of exercise-related FNDC5/irisin in memory and Alzheimer's disease
de Freitas, G. B., Lourenco, M. V., & De Felice, F. G. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15039 · Cited by 120
“These effects were more recently shown to partly depend on the integrin αVβ5 in fat and bone (Kim et al., 2018).”
Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
Estell, E. G., Le, P. T., Vegting, Y., Kim, H., Wrann, C. D., Bouxsein, M., Nagano, K., Baron, R., Spiegelman, B. M., & Rosen, C. J. (2020) · eLife · doi:10.7554/elife.58172 · Cited by 120
Self-citation
Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2
Zhu, W., Sahar, N.-E., Javaid, H. M. A., Pak, E. S., Liang, G., Wang, Y., Ha, H., & Huh, J. Y. (2021) · Cells · doi:10.3390/cells10123306 · Cited by 119
Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
Bi, J., Zhang, J., Ren, Y., Du, Z., Li, T., Wang, T., Zhang, L., Wang, M., Wu, Z., Lv, Y., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14811 · Cited by 113
The crosstalk between bone remodeling and energy metabolism: A translational perspective
Karsenty, G., & Khosla, S. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.04.010 · Cited by 113
Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging
Mancinelli, R., Checcaglini, F., Coscia, F., Gigliotti, P. V., Fulle, S., & Fanò, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168520 · Cited by 113
Exercise-Linked Skeletal Irisin Ameliorates Diabetes-Associated Osteoporosis by Inhibiting the Oxidative Damage–Dependent miR-150-FNDC5/Pyroptosis Axis
Behera, J., Ison, J., Voor, M. J., & Tyagi, N. (2022) · Diabetes · doi:10.2337/db21-0573 · Cited by 115
Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders
Nay, K., Smiles, W. J., Kaiser, J., McAloon, L. M., Loh, K., Galić, S., Oakhill, J. S., Gundlach, A. L., & Scott, J. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084052 · Cited by 112
Irisin, a fascinating field in our times
Bao, J., She, Q.-Y., Hu, P., Jia, N., & Li, A. (2022) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2022.06.003 · Cited by 111
AMPK and the Endocrine Control of Metabolism
Townsend, L. K., & Steinberg, G. R. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad012 · Cited by 114
FNDC5/Irisin attenuates diabetic cardiomyopathy in a type 2 diabetes mouse model by activation of integrin αV/β5-AKT signaling and reduction of oxidative/nitrosative stress
Lin, C., Guo, Y., Xia, Y., Li, C., Xu, X., Qi, T., Zhang, F., Fan, M., Hu, G., Zhao, H., et al. (2021) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.06.013 · Cited by 103
Exerkine fibronectin type-III domain-containing protein 5/irisin-enriched extracellular vesicles delay vascular ageing by increasing SIRT6 stability
Chi, C., Fu, H., Li, Y., Zhang, G., Zeng, F., Ji, Q., Shen, Q., Wang, X.-J., Li, Z., Zhou, C., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac431 · Cited by 103
Self-citation
Irisin reduces inflammatory signaling pathways in inflammation-mediated metabolic syndrome
Slate‐Romano, J., Yano, N., & Zhao, T. C. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111676 · Cited by 105
How does the skeletal muscle communicate with the brain in health and disease?
Isaac, A. R., Lima‐Filho, R. A. S., & Lourenco, M. V. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108744 · Cited by 99
Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis
Liao, Q., Qu, S., Tang, L., Li, L.-P., He, D., Zeng, C., & Wang, W. E. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0230-z · Cited by 94
Myokines and Heart Failure: Challenging Role in Adverse Cardiac Remodeling, Myopathy, and Clinical Outcomes
Berezin, A. Е., Berezin, A. A., & Lichtenauer, M. (2021) · Disease Markers · doi:10.1155/2021/6644631 · Cited by 97
Effects of irisin on the dysfunction of blood–brain barrier in rats after focal cerebral ischemia/reperfusion
Guo, P., Jin, Z. Y., Wu, H., Li, X., Ke, J., Zhang, Z., & Zhao, Q. (2019) · Brain and Behavior · doi:10.1002/brb3.1425 · Cited by 92
“It is not only a compound muscle factor medium, but also a fat factor (Kim et al., 2018).”
A FAK/HDAC5 signaling axis controls osteocyte mechanotransduction
Sato, T., Verma, S., Andrade, C. D. C., Omeara, M., Campbell, N., Wang, J. S., Cetinbas, M., Lang, A., Ausk, B. J., Brooks, D. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17099-3 · Cited by 86
Self-citation
Searching for the link between inflammaging and sarcopenia
Wang, T. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101611 · Cited by 90
Exercise hormone irisin mitigates endothelial barrier dysfunction and microvascular leakage–related diseases
Bi, J., Zhang, J., Ren, Y., Du, Z., Zhang, Y., Liu, C., Wang, Y., Zhang, L., Shi, Z., Wu, Z., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.136277 · Cited by 89
Irisin: Still chasing shadows
Albrecht, E., Schering, L., Buck, F., Vlach, K., Schober, H., Drevon, C. A., & Maak, S. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.016 · Cited by 93
Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease
Zhang, X., Xu, S., Hu, Y. H., Liu, Q., Liu, C., Chai, H., Luo, Y., Jin, L., & Li, S. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00453-9 · Cited by 97
Irisin as an agent for protecting against osteoporosis: A review of the current mechanisms and pathways
Hu, X., Wang, Z., Wang, W., Cui, P., Kong, C., Chen, X., & Lu, S. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.09.001 · Cited by 94
Irisin drives macrophage anti-inflammatory differentiation via JAK2-STAT6-dependent activation of PPARγ and Nrf2 signaling
Tu, Y., Liu, J., Kong, D., Guo, X., Li, J., Long, Z., Peng, J., Wang, Z., Wu, H., Liu, P., et al. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.03.014 · Cited by 89
Molecular insights of exercise therapy in disease prevention and treatment
Walzik, D., Chirino, T. Y. W., Zimmer, P., & Joisten, N. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01841-0 · Cited by 95
The Central Role of Osteocytes in the Four Adaptive Pathways of Bone’s Mechanostat
Hughes, J. M., Castellani, C. M., Popp, K. L., Guerriere, K. I., Matheny, R. W., Nindl, B. C., & Bouxsein, M. (2020) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000225 · Cited by 86
Self-citation
Integrin-Ligand Interactions in Inflammation, Cancer, and Metabolic Disease: Insights Into the Multifaceted Roles of an Emerging Ligand Irisin
Park, E. J., Myint, P. K., Ito, A., Appiah, M. G., Darkwah, S. O., Kawamoto, E., & Shimaoka, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.588066 · Cited by 84
Physical Exercise-Induced Myokines in Neurodegenerative Diseases
Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79
Fibronectin type III domain‐containing 5 improves aging‐related cardiac dysfunction in mice
Hu, C., Zhang, X., Hu, M., Teng, T., Yuan, Y., Song, P. K., Kong, C., Xu, S., Ma, Z., & Tang, Q. (2022) · Aging Cell · doi:10.1111/acel.13556 · Cited by 80
Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice
He, Z., Li, H., Han, X., Zhou, F., Du, J., Yang, Y., Xu, Q., Zhang, S., Zhang, S., Zhao, N., et al. (2020) · Bone · doi:10.1016/j.bone.2020.115573 · Cited by 76
The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients
Chang, C. L., Huang, S. Y., Hsu, Y. C., Chin, T. H., & Soong, Y. K. (2019) · Scientific Reports · doi:10.1038/s41598-019-42061-9 · Cited by 80
The “irisin system”: From biological roles to pharmacological and nutraceutical perspectives
Flori, L., Testai, L., & Calderone, V. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118954 · Cited by 81
Irisin: A New Code Uncover the Relationship of Skeletal Muscle and Cardiovascular Health During Exercise
Ma, C., Ding, H., Deng, Y., Liu, H., Xiong, X., & Yang, Y. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.620608 · Cited by 76
Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models
Feraco, A., Gorini, S., Armani, A., Camajani, E., Rizzo, M., & Caprio, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179327 · Cited by 78
Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice
Xue, Y., Hu, S., Chen, C., He, J., Sun, J., Jin, Y., Zhang, Y., Zhu, G., Shi, Q., & Rui, Y. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.63505 · Cited by 81
The effects of both age and sex on irisin levels in paired plasma and cerebrospinal fluid in healthy humans
Ruan, Q., Huang, Y., Yang, L., Ruan, J., Gu, W., Zhang, X., Zhang, Y., Zhang, W., & Yu, Z. (2019) · Peptides · doi:10.1016/j.peptides.2019.01.004 · Cited by 79
Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90α
Mu, A., Wales, T. E., Zhou, H., Draga-Coletă, S.-V., Gorgulla, C., Blackmore, K. A., Mittenbühler, M. J., Kim, C. R., Laznik-Bogoslavski, D., Zhang, Q., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.05.008 · Cited by 82
Self-citation
Irisin reverses insulin resistance in C2C12 cells via the p38-MAPK-PGC-1α pathway
Ye, X., Shen, Y., Ni, C., Ye, J., Xin, Y., Zhang, W., & Ren, Y. (2019) · Peptides · doi:10.1016/j.peptides.2019.170120 · Cited by 73
Hormesis in Health and Chronic Diseases
Li, X., Yang, T., & Sun, Z. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.08.007 · Cited by 79
The Emerging Role of Irisin in Cardiovascular Diseases
Fu, J., Li, F., Tang, Y., Cai, L., Zeng, C., Yang, Y., & Yang, J. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.121.022453 · Cited by 78
Role of Physical Activity in Bone–Muscle Crosstalk: Biological Aspects and Clinical Implications
Cariati, I., Bonanni, R., Onorato, F., Mastrogregori, A., Rossi, D., Iundusi, R., Gasbarra, E., Tancredi, V., & Tarantino, U. (2021) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk6020055 · Cited by 78
Irisin deficiency disturbs bone metabolism
Zhu, X., Li, X., Wang, X., Chen, T., Tao, F., Liu, C.-J., Tu, Q., Shen, G., & Chen, J. J. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29894 · Cited by 72
Functional effects of muscle PGC-1alpha in aged animals
Yang, S., Loro, E., Wada, S., Kim, B., Tseng, W.-J., Li, K., Khurana, T. S., & Arany, Z. (2020) · Skeletal Muscle · doi:10.1186/s13395-020-00231-8 · Cited by 68
Bone-Muscle Mutual Interactions
Lara-Castillo, N., & Johnson, M. L. (2020) · Current Osteoporosis Reports · doi:10.1007/s11914-020-00602-6 · Cited by 70
Factors mediating exercise‐induced organ crosstalk
Sabaratnam, R., Wojtaszewski, J. F. P., & Højlund, K. (2022) · Acta Physiologica · doi:10.1111/apha.13766 · Cited by 70
Irisin Exerts Inhibitory Effect on Adipogenesis Through Regulation of Wnt Signaling
Ma, E. B., Sahar, N.-E., Jeong, M., & Huh, J. Y. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01085 · Cited by 69
Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression
Chen, Z., Zhang, Y., Zhao, F., Yin, C., Yang, C., Wang, X., Wu, Z., Liang, S., Li, D., Lin, X., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041259 · Cited by 64
Irisin: A Multifaceted Hormone Bridging Exercise and Disease Pathophysiology
Paoletti, I., & Coccurello, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413480 · Cited by 81
Irisin and Bone: From Preclinical Studies to the Evaluation of Its Circulating Levels in Different Populations of Human Subjects
Colaianni, G., Sanesi, L., Storlino, G., Brunetti, G., Colucci, S. C., & Grano, M. (2019) · Cells · doi:10.3390/cells8050451 · Cited by 63
Adipose–Muscle Crosstalk in Age-Related Metabolic Disorders: The Emerging Roles of Adipo-Myokines
Fang, P., She, Y., Yu, M., Min, W., Shang, W., & Zhang, Z. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101829 · Cited by 62
Circular RNA AFF4 modulates osteogenic differentiation in BM-MSCs by activating SMAD1/5 pathway through miR-135a-5p/FNDC5/Irisin axis
Liu, C., Liu, A., Zhong, D., Wang, C.-G., Yu, M. R., Zhang, H.-W., Xiao, H., Liu, J.-H., Zhang, J., & Yin, K. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03877-4 · Cited by 60
The Role of Irisin in Cancer Disease
Pinkowska, A., Podhorska‐Okołów, M., Dzięgiel, P., & Nowińska, K. (2021) · Cells · doi:10.3390/cells10061479 · Cited by 62
Muscle–brain crosstalk mediated by exercise-induced myokines - insights from experimental studies
Kostka, M., Morys, J., Małecki, A., & Nowacka-Chmielewska, M. M. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1488375 · Cited by 75
Irisin promotes fracture healing by improving osteogenesis and angiogenesis
Kan, T., He, Z., Du, J., Xu, M., Cui, J., Han, X., Tong, D., Li, H., Yan, M., & Yu, Z. (2022) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2022.07.006 · Cited by 60
Exercise Ameliorates Emphysema Of Cigarette Smoke-Induced COPD In Mice Through The Exercise-Irisin-Nrf2 Axis
Kubo, H., Asai, K., Kojima, K., Sugitani, A., Kyomoto, Y., Okamoto, A., Yamada, K., Ijiri, N., Watanabe, T., Hirata, K., et al. (2019) · International Journal of COPD · doi:10.2147/copd.s226623 · Cited by 60
Disordered metabolism in mice lacking irisin
Luo, Y., Qiao, X., Ma, Y., Deng, H., Xu, C. C., & Xu, L. (2020) · Scientific Reports · doi:10.1038/s41598-020-74588-7 · Cited by 60
Integrin adhesion in brain assembly: From molecular structure to neuropsychiatric disorders
Jaudon, F., Thalhammer, A., & Cingolani, L. A. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14859 · Cited by 59
The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity
Li, H., Wang, F., Mu, Y., Sun, J., Zhao, Y. C., & Tang, D. (2021) · International Journal of Endocrinology · doi:10.1155/2021/6572342 · Cited by 67
Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue
Georgiadi, A., Lopez‐Salazar, V., El‐Merahbi, R., Karikari, R. A., Ma, X., Mourão, A., Klepac, K., Bühler, L., Alfaro, A. J., Kaczmarek, I., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22579-1 · Cited by 59
Irisin and Autophagy: First Update
Pesce, M., Ballerini, P., Paolucci, T., Puca, I., Farzaei, M. H., & Patruno, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207587 · Cited by 59
Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics
Wang, F., Wu, R., Chen, Y., Ko, J., Jahr, H., & Lian, W. (2021) · Antioxidants · doi:10.3390/antiox10091394 · Cited by 57
Effect of Chronic Resistance Training on Circulating Irisin: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Cosio, P. L., Crespo-Posadas, M., Velarde-Sotres, Á., & Pelaez, M. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18052476 · Cited by 56
Irisin and Incretin Hormones: Similarities, Differences, and Implications in Type 2 Diabetes and Obesity
Marrano, N., Biondi, G., Borrelli, A., Cignarelli, A., Perrini, S., Laviola, L., Giorgino, F., & Natalicchio, A. (2021) · Biomolecules · doi:10.3390/biom11020286 · Cited by 56
Irisin: An anti-inflammatory exerkine in aging and redox-mediated comorbidities
Trettel, C. D. S., Pelozin, B. R. D. A., Barros, M. P., Bachi, A. L. L., Braga, P. G. S., Momesso, C. M., Furtado, G. E., Valente, P. A., de Oliveira, E. M., Hogervorst, E., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1106529 · Cited by 56

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks