Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
- Maine Medical Center Research Institute, United States
- Dana Farber Cancer Institute, United States
- MGH/Harvard Medical School, United States
- Harvard Medical School, United States
- Harvard University, United States
Abstract
The myokine irisin facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In the current study we investigated whether irisin also directly regulates osteoclasts. In vitro, irisin (2-10 ng/mL) increased osteoclast differentiation in C57BL/6J mouse bone marrow progenitors; this increase was blocked by a neutralizing antibody to integrin αVβ5. Irisin also increased bone resorption on several substrates in situ. RNAseq revealed differential gene expression induced by irisin including upregulation of markers for osteoclast differentiation and resorption, as well as osteoblast-stimulating 'clastokines'. Forced expression of the irisin precursor Fndc5 in transgenic C57BL/6J mice resulted in low bone mass at three ages, and greater in vitro osteoclastogenesis from Fndc5-transgenic bone marrow progenitors. This work demonstrates that irisin acts directly on osteoclast progenitors to increase differentiation and promote bone resorption, supporting the tenet that irisin not only stimulates bone remodeling but may also be an important counter-regulatory hormone.
Data availability
All data generated or analysed during this study are included in the manuscript figures and supplementary tables.
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Author details
Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (F32AR077382)
- Eben G Estell
- Roland Baron
- Bruce M Spiegelman
- Clifford J Rosen
National Institute on Aging (U19AG060917)
- Eben G Estell
- Clifford J Rosen
National Institute of General Medical Sciences (U54GM115516-01A1)
- Clifford J Rosen
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK112374)
- Clifford J Rosen
National Institute of General Medical Sciences (1P20GM121301)
- Clifford J Rosen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All wild type primary cell progenitors for osteoclast cultures with exogenous irisin were obtained from tissue harvested from male and female C57BL6/J mice housed and treated under a protocol approved by the Maine Medical Center Research Institute IACUC (1914)
Copyright
© 2020, Estell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
eLife 9:e58172.
https://doi.org/10.7554/eLife.58172
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