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Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes

PURPOSE: Bone remodeling is affected by mechanical stimulation. Osteocytes are the primary mechanical load-sensing cells in the bone, and can regulate osteoblast and osteoclast activity, thus playing a key role in bone remodeling. Further, bone mass during exercise is also regulated by Leukemia inhi...

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Autores principales: Du, Jingke, Yang, Jiancheng, He, Zihao, Cui, Junqi, Yang, Yiqi, Xu, Mingming, Qu, Xinhua, Zhao, Ning, Yan, Mengning, Li, Hanjun, Yu, Zhifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726425/
https://www.ncbi.nlm.nih.gov/pubmed/33324677
http://dx.doi.org/10.3389/fmolb.2020.585056
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author Du, Jingke
Yang, Jiancheng
He, Zihao
Cui, Junqi
Yang, Yiqi
Xu, Mingming
Qu, Xinhua
Zhao, Ning
Yan, Mengning
Li, Hanjun
Yu, Zhifeng
author_facet Du, Jingke
Yang, Jiancheng
He, Zihao
Cui, Junqi
Yang, Yiqi
Xu, Mingming
Qu, Xinhua
Zhao, Ning
Yan, Mengning
Li, Hanjun
Yu, Zhifeng
author_sort Du, Jingke
collection PubMed
description PURPOSE: Bone remodeling is affected by mechanical stimulation. Osteocytes are the primary mechanical load-sensing cells in the bone, and can regulate osteoblast and osteoclast activity, thus playing a key role in bone remodeling. Further, bone mass during exercise is also regulated by Leukemia inhibitory factor (LIF). This study aimed to investigate the role of LIF in the mechanical response of the bone, in vivo and in vitro, and to elucidate the mechanism by which osteocytes secrete LIF to regulate osteoblasts and osteoclasts. METHODS: A tail-suspension (TS) mouse model was used in this study to mimic muscular disuse. ELISA and immunohistochemistry were performed to detect bone and serum LIF levels. Micro-computed tomography (CT) of the mouse femurs was performed to measure three-dimensional bone structure parameters. Fluid shear stress (FSS) and microgravity simulation experiments were performed to study mechanical stress-induced LIF secretion and its resultant effects. Bone marrow macrophages (BMMs) and bone mesenchymal stem cells (BMSCs) were cultured to induce in vitro osteoclastogenesis and osteogenesis, respectively. RESULTS: Micro-CT results showed that TS mice exhibited deteriorated bone microstructure and lower serum LIF expression. LIF secretion by osteocytes was promoted by FSS and was repressed in a microgravity environment. Further experiments showed that LIF could elevate the tartrate-resistant acid phosphatase activity in BMM-derived osteoclasts through the STAT3 signaling pathway. LIF also enhanced alkaline phosphatase staining and osteogenesis-related gene expression during the osteogenic differentiation of BMSCs. CONCLUSION: Mechanical loading affected LIF expression levels in osteocytes, thereby altering the balance between osteoclastogenesis and osteogenesis.
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spelling pubmed-77264252020-12-14 Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes Du, Jingke Yang, Jiancheng He, Zihao Cui, Junqi Yang, Yiqi Xu, Mingming Qu, Xinhua Zhao, Ning Yan, Mengning Li, Hanjun Yu, Zhifeng Front Mol Biosci Molecular Biosciences PURPOSE: Bone remodeling is affected by mechanical stimulation. Osteocytes are the primary mechanical load-sensing cells in the bone, and can regulate osteoblast and osteoclast activity, thus playing a key role in bone remodeling. Further, bone mass during exercise is also regulated by Leukemia inhibitory factor (LIF). This study aimed to investigate the role of LIF in the mechanical response of the bone, in vivo and in vitro, and to elucidate the mechanism by which osteocytes secrete LIF to regulate osteoblasts and osteoclasts. METHODS: A tail-suspension (TS) mouse model was used in this study to mimic muscular disuse. ELISA and immunohistochemistry were performed to detect bone and serum LIF levels. Micro-computed tomography (CT) of the mouse femurs was performed to measure three-dimensional bone structure parameters. Fluid shear stress (FSS) and microgravity simulation experiments were performed to study mechanical stress-induced LIF secretion and its resultant effects. Bone marrow macrophages (BMMs) and bone mesenchymal stem cells (BMSCs) were cultured to induce in vitro osteoclastogenesis and osteogenesis, respectively. RESULTS: Micro-CT results showed that TS mice exhibited deteriorated bone microstructure and lower serum LIF expression. LIF secretion by osteocytes was promoted by FSS and was repressed in a microgravity environment. Further experiments showed that LIF could elevate the tartrate-resistant acid phosphatase activity in BMM-derived osteoclasts through the STAT3 signaling pathway. LIF also enhanced alkaline phosphatase staining and osteogenesis-related gene expression during the osteogenic differentiation of BMSCs. CONCLUSION: Mechanical loading affected LIF expression levels in osteocytes, thereby altering the balance between osteoclastogenesis and osteogenesis. Frontiers Media S.A. 2020-11-26 /pmc/articles/PMC7726425/ /pubmed/33324677 http://dx.doi.org/10.3389/fmolb.2020.585056 Text en Copyright © 2020 Du, Yang, He, Cui, Yang, Xu, Qu, Zhao, Yan, Li and Yu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Du, Jingke
Yang, Jiancheng
He, Zihao
Cui, Junqi
Yang, Yiqi
Xu, Mingming
Qu, Xinhua
Zhao, Ning
Yan, Mengning
Li, Hanjun
Yu, Zhifeng
Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes
title Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes
title_full Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes
title_fullStr Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes
title_full_unstemmed Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes
title_short Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes
title_sort osteoblast and osteoclast activity affect bone remodeling upon regulation by mechanical loading-induced leukemia inhibitory factor expression in osteocytes
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726425/
https://www.ncbi.nlm.nih.gov/pubmed/33324677
http://dx.doi.org/10.3389/fmolb.2020.585056
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