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Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo

Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. In vitro, irisin (2–10 ng/mL) increased osteoclast differentiation...

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Autores principales: Estell, Eben G, Le, Phuong T, Vegting, Yosta, Kim, Hyeonwoo, Wrann, Christiane, Bouxsein, Mary L, Nagano, Kenichi, Baron, Roland, Spiegelman, Bruce M, Rosen, Clifford J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444909/
https://www.ncbi.nlm.nih.gov/pubmed/32780016
http://dx.doi.org/10.7554/eLife.58172
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author Estell, Eben G
Le, Phuong T
Vegting, Yosta
Kim, Hyeonwoo
Wrann, Christiane
Bouxsein, Mary L
Nagano, Kenichi
Baron, Roland
Spiegelman, Bruce M
Rosen, Clifford J
author_facet Estell, Eben G
Le, Phuong T
Vegting, Yosta
Kim, Hyeonwoo
Wrann, Christiane
Bouxsein, Mary L
Nagano, Kenichi
Baron, Roland
Spiegelman, Bruce M
Rosen, Clifford J
author_sort Estell, Eben G
collection PubMed
description Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. In vitro, irisin (2–10 ng/mL) increased osteoclast differentiation in C57BL/6J mouse bone marrow progenitors; however, this increase was blocked by a neutralizing antibody to integrin α(V)β(5). 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 lower bone mass at three ages and greater in vitro osteoclastogenesis from Fndc5-transgenic bone marrow progenitors. This study 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.
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spelling pubmed-74449092020-08-26 Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo Estell, Eben G Le, Phuong T Vegting, Yosta Kim, Hyeonwoo Wrann, Christiane Bouxsein, Mary L Nagano, Kenichi Baron, Roland Spiegelman, Bruce M Rosen, Clifford J eLife Cell Biology Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. In vitro, irisin (2–10 ng/mL) increased osteoclast differentiation in C57BL/6J mouse bone marrow progenitors; however, this increase was blocked by a neutralizing antibody to integrin α(V)β(5). 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 lower bone mass at three ages and greater in vitro osteoclastogenesis from Fndc5-transgenic bone marrow progenitors. This study 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. eLife Sciences Publications, Ltd 2020-08-11 /pmc/articles/PMC7444909/ /pubmed/32780016 http://dx.doi.org/10.7554/eLife.58172 Text en © 2020, Estell et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Estell, Eben G
Le, Phuong T
Vegting, Yosta
Kim, Hyeonwoo
Wrann, Christiane
Bouxsein, Mary L
Nagano, Kenichi
Baron, Roland
Spiegelman, Bruce M
Rosen, Clifford J
Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
title Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
title_full Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
title_fullStr Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
title_full_unstemmed Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
title_short Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
title_sort irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444909/
https://www.ncbi.nlm.nih.gov/pubmed/32780016
http://dx.doi.org/10.7554/eLife.58172
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