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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“Interactions of the αV family of integrins with extracellular matrix proteins such as osteopontin and vitronectin lead to adhesion of osteoclasts to the bone surface followed by bone resorption (Duong et al., 2000; Duong and Rodan, 1998; Flores et al., 1992; Horton et al., 1991).”
Zhang, J., Valverde, P., Zhu, X., Murray, D., Wu, Y., Yu, L., Jiang, H., Dard, M. M., Huang, J., Zhi-wei, X., et al. (2017) · Bone Research · doi:10.1038/boneres.2016.56 · Cited by 175 · cited 1× · see citing works
“These effects are related mainly to known benefits of exercise, such as strengthening bones, increasing energy expenditure and improving cognition (Bostrom et al., 2012; Colaianni et al., 2015; Colaianni et al., 2017; Lee et al., 2014; Wrann et al., 2013; Zhang et al., 2017).”
Arginyl-glycyl-aspartic acid sequences and fibrinogen binding to platelets
Plow, E., Pierschbacher, M. D., Ruoslahti, E. I., Marguerie, G. A., & Ginsberg, M. H. (1987) · Blood · doi:10.1182/blood.v70.1.110.110 · Cited by 169 · see citing works
Bone Health in Endurance Athletes
Scofield, K. L., & Hecht, S. S. (2012) · Current Sports Medicine Reports · doi:10.1249/jsr.0b013e3182779193 · Cited by 164 · cited 1× · see citing works
“Importantly, results from endurance exercise trials, particularly in the elderly, are even less convincing, with some studies showing preservation of bone mass and others showing no effect or even bone loss (Braam et al., 2003; Duckham et al., 2013; Scofield and Hecht, 2012).”
Osteocyte Remodeling of the Perilacunar and Pericanalicular Matrix
Qing, H., & Bonewald, L. F. (2009) · International Journal of Oral Science · doi:10.4248/ijos.09019 · Cited by 152 · cited 1× · see citing works
“Emerging evidence suggests that osteocytes can also directly resorb bone during periods of excessive calcium demand (Qing and Bonewald, 2009) or after ovariectomy (Almeida et al.”
Self-citationSclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading
Spatz, J., Ellman, R., Cloutier, A., Louis, L. D., Vliet, M. V., Suva, L. J., Dwyer, D., Stolina, M., Ke, H. Z., & Bouxsein, M. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1807 · Cited by 143 · cited 1× · see citing works
“Analysis of femur using μCT—We used high-resolution desktop microcomputed tomography imaging (μCT40, Scanco Medical, Brüttisellen, Switzerland) for analysis as previously reported (Spatz et al., 2013).”
Self-citationThi, M. M., Suadicani, S. O., Schaffler, M. B., Weinbaum, S., & Spray, D. C. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321210110 · Cited by 141 · see citing works
Structural basis for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin
Agthoven, J. F. V., Xiong, J.-P., Alonso, J. L., Rui, X., Adair, B. D., Goodman, S. L., & Arnaout, M. A. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2797 · Cited by 135 · see citing works
Molecular basis for the targeted binding of RGD-containing peptide to integrin αVβ3
Yu, Y.-P., Wang, Q., Liu, Y., & Xie, Y. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.10.072 · Cited by 131 · see citing works
Miller, W. H., Alberts, D., Bhatnagar, P. K., Bondinell, W. E., Callahan, J. F., Calvo, R. R., Cousins, R. D., Erhard, K. F., Heerding, D. A., Keenan, R. M., et al. (1999) · Journal of Medicinal Chemistry · doi:10.1021/jm990446u · Cited by 119 · see citing works
Biochemical characterization of the binding of echistatin to integrin alphavbeta3 receptor.
Kumar, C. C., Huiming-Nie, C. P. R., Rogers, C. P., Malkowski, M., Maxwell, E., Catino, J. J., & Armstrong, L. (1997) · PubMed · Cited by 106 · see citing works
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“Consistent with the latter effect, brief bouts of endurance training have been shown to increase bone resorption and stimulate sclerostin, an endogenous inhibitor of bone formation (Baron and Kneissel, 2013; Kohrt et al., 2018; Pickering et al., 2017).”
Ovariectomy/Orchidectomy in Rodents
Idris, A. I. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-415-5_34 · Cited by 88 · cited 24× · see citing works
“Furthermore, deficiency of FNDC5 inhibited OVX-induced perilacunar enlargement. a manifestation of osteocytic osteolysis, indicating that the phenotype is at least mediated partly through an inactivation of osteocyte function(s), as well as through inhibition of osteoclast number and function.”
InfluentialKeppel, T. R., & Weis, D. D. (2014) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-014-1033-6 · Cited by 85 · see citing works
Factors Affecting Bone Loss in Female Endurance Athletes
Braam, L. A. J. L. M., Knapen, M. H. J., Geusens, P., Brouns, F. J. P. H., & Vermeer, C. (2003) · The American Journal of Sports Medicine · doi:10.1177/03635465030310062601 · Cited by 80 · see citing works
Integrin-mediated signaling in the regulation of osteoclast adhesion and activation
Duong, L. T. (1998) · Frontiers in bioscience · doi:10.2741/a319 · Cited by 70 · see citing works
Sclerostin antibodies in osteoporosis: latest evidence and therapeutic potential
McClung, M. R. (2017) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x17726744 · Cited by 70 · cited 1× · see citing works
“Anti-sclerostin antibodies increase bone mass dramatically in humans but also may have cardiovascular side-effects that could limit their use in practice (McClung, 2017).”
Human Integrin αvβ5: Homology Modeling and Ligand Binding
Marinelli, L., Gottschalk, K., Meyer, A., Novellino, E., & Kessler, H. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm030635j · Cited by 57 · cited 2× · see citing works
“Interestingly, these regions or motifs in integrin β5 have been previously reported to interact with ligands such as fibronectin, osteopontin and vitronectin (Hu et al., 1995; Humphries et al., 2006; Marinelli et al., 2004; Smith et al., 1990; Van Agthoven et al., 2014).”
Lark, M. W., Stroup, G. B., Dodds, R. A., Kapadia, R. D., Hoffman, S. J., Hwang, S. M., James, I. E., Lechowska, B., Liang, X. G., Rieman, D. J., et al. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.2.319 · Cited by 56 · cited 4× · see citing works
“In addition, we tested irisin-induced signaling with other specific inhibitors for integrin αV, such as cyclo RGDyK and SB273005 (Chen et al., 2004; Dechantsreiter et al., 1999; Lark et al., 2001; Miller et al., 2000; Yu et al., 2014).”
InfluentialNeogenin Interacts with Hemojuvelin through Its Two Membrane-Proximal Fibronectin Type III Domains
Yang, F., West, A. P., Allendorph, G. P., Choe, S., & Björkman, P. J. (2008) · Biochemistry · doi:10.1021/bi800036h · Cited by 56 · cited 1× · see citing works
“Importantly, they bind to a wide range of different receptors, including fibroblast growth factor receptor and hemojuvelin (Kiselyov et al., 2003; Yang et al., 2008).”
Serum Sclerostin Increases After Acute Physical Activity
Pickering, M., Simon, M., Sornay‐Rendu, E., Chikh, K., Carlier, M.-C., Raby, A.-L., Szulc, P., & Confavreux, C. B. (2017) · Calcified Tissue International · doi:10.1007/s00223-017-0272-5 · Cited by 53 · see citing works
Muscular strength and bone mineral density in haemodialysis patients
Spindler, A. J., Paz, S., Berman, A., Lucero, E., Contino, N., Peñalba, A., Tirado, S., Santana, M., & Zeballos, Á. C. (1997) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/12.1.128 · Cited by 40 · see citing works
Bone Geometry According to Menstrual Function in Female Endurance Athletes
Duckham, R. L., Peirce, N. S., Bailey, C. A., Summers, G. D., Cameron, N., & Brooke-Wavell, K. S. F. (2013) · Calcified Tissue International · doi:10.1007/s00223-013-9700-3 · Cited by 26 · cited 1× · see citing works
“Importantly, results from endurance exercise trials, particularly in the elderly, are even less convincing, with some studies showing preservation of bone mass and others showing no effect or even bone loss (Braam et al., 2003; Duckham et al., 2013; Scofield and Hecht, 2012).”
Resistance exercise training restores bone mineral density in renal transplant recipients
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Guo, L. E., Ding, W., & Zheng, L. (2014) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2014.8691 · Cited by 8 · see citing works
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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 · see citing works
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Exercise hormone irisin is a critical regulator of cognitive function
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Self-citationThe Regulation of Bone Metabolism and Disorders by Wnt Signaling
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Irisin: A Hope in Understanding and Managing Obesity and Metabolic Syndrome
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CD81 controls beige fat progenitor cell growth and energy balance via FAK signaling
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Self-citationMyokines: The endocrine coupling of skeletal muscle and bone
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Sarcopenia, osteoporosis and frailty
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Progress and Challenges in the Biology of FNDC5 and Irisin
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Use it or lose it to age: A review of bone and muscle communication
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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 · see citing works
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 178 · see citing works
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 171 · see citing works
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 170 · see citing works
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 173 · see citing works
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 · see citing works
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 163 · see citing works
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 166 · see citing works
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 173 · see citing works
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 158 · see citing works
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 154 · see citing works
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 149 · see citing works
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 145 · see citing works
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 139 · see citing works
Young, M. F., Valaris, S., & Wrann, C. D. (2019) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2019.02.007 · Cited by 136 · see citing works
Self-citationMultiple 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 143 · see citing works
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 131 · see citing works
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 127 · see citing works
Self-citationAmelioration 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 · see citing works
Self-citationMechanisms 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 131 · see citing works
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 · see citing works
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 128 · see citing works
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 · see citing works
“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 119 · see citing works
Self-citationExercise-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 116 · see citing works
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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 · see citing works
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 108 · see citing works
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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 108 · see citing works
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 102 · see citing works
AMPK and the Endocrine Control of Metabolism
Townsend, L. K., & Steinberg, G. R. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad012 · Cited by 101 · see citing works
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Self-citationIrisin 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 97 · see citing works
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 94 · see citing works
Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis
Liao, Q., Qu, S., Tang, L.-X., Li, L.-P., He, D.-F., Zeng, C.-Y., & Wang, W. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0230-z · Cited by 91 · see citing works
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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 · see citing works
“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 · see citing works
Self-citationSearching for the link between inflammaging and sarcopenia
Wang, T. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101611 · Cited by 88 · see citing works
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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 87 · see citing works
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 90 · see citing works
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 · see citing works
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 89 · see citing works
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 83 · see citing works
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Physical Exercise-Induced Myokines in Neurodegenerative Diseases
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Fibronectin type III domain‐containing 5 improves aging‐related cardiac dysfunction in mice
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The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients
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The “irisin system”: From biological roles to pharmacological and nutraceutical perspectives
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Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90α
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Self-citationIrisin reverses insulin resistance in C2C12 cells via the p38-MAPK-PGC-1α pathway
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Hormesis in Health and Chronic Diseases
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The Emerging Role of Irisin in Cardiovascular Diseases
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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 72 · see citing works
Irisin deficiency disturbs bone metabolism
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Functional effects of muscle PGC-1alpha in aged animals
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Bone-Muscle Mutual Interactions
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Factors mediating exercise‐induced organ crosstalk
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Irisin Exerts Inhibitory Effect on Adipogenesis Through Regulation of Wnt Signaling
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Irisin: A Multifaceted Hormone Bridging Exercise and Disease Pathophysiology
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Adipose–Muscle Crosstalk in Age-Related Metabolic Disorders: The Emerging Roles of Adipo-Myokines
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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 61 · see citing works
The Role of Irisin in Cancer Disease
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Muscle–brain crosstalk mediated by exercise-induced myokines - insights from experimental studies
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Irisin promotes fracture healing by improving osteogenesis and angiogenesis
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Disordered metabolism in mice lacking irisin
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Integrin adhesion in brain assembly: From molecular structure to neuropsychiatric disorders
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The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity
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Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue
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Irisin and Autophagy: First Update
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Irisin: An anti-inflammatory exerkine in aging and redox-mediated comorbidities
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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)
- 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 › Epidemiology › 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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