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Connective Tissue Growth Factor From Periosteal Tartrate Acid Phosphatase-Positive Monocytes Direct Skeletal Stem Cell Renewal and Fate During Bone Healing

The periosteum is critical for bone healing. Studies have shown that the periosteum contains periosteal stem cells (PSCs) with multidirectional differentiation potential and self-renewal ability. PSCs are activated in early fracture healing and are committed to the chondrocyte lineage, which is the...

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Autores principales: Bai, Yun, Yu, Tao, Deng, Jiezhong, Yang, Yusheng, Tan, Jiulin, Dai, Qijie, Zhang, Zehua, Dong, Shiwu, Xu, Jianzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476870/
https://www.ncbi.nlm.nih.gov/pubmed/34595178
http://dx.doi.org/10.3389/fcell.2021.730095
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author Bai, Yun
Yu, Tao
Deng, Jiezhong
Yang, Yusheng
Tan, Jiulin
Dai, Qijie
Zhang, Zehua
Dong, Shiwu
Xu, Jianzhong
author_facet Bai, Yun
Yu, Tao
Deng, Jiezhong
Yang, Yusheng
Tan, Jiulin
Dai, Qijie
Zhang, Zehua
Dong, Shiwu
Xu, Jianzhong
author_sort Bai, Yun
collection PubMed
description The periosteum is critical for bone healing. Studies have shown that the periosteum contains periosteal stem cells (PSCs) with multidirectional differentiation potential and self-renewal ability. PSCs are activated in early fracture healing and are committed to the chondrocyte lineage, which is the basis of callus formation. However, the mechanism by which PSCs are activated and committed to chondrocytes in bone regeneration remains unclear. Here, we show that tartrate acid phosphatase (TRAP)-positive monocytes secrete CTGF to activate PSCs during bone regeneration. The loss function of TRAP-positive monocytes identifies their specific role during bone healing. Then, the secreted CTGF promotes endochondral ossification and activates PSCs in mouse bone fracture models. The secreted CTGF enhances PSC renewal by upregulating the expression of multiple pluripotent genes. CTGF upregulates c-Jun expression through αVβ5 integrin. Then, c-Jun transcription activates the transcription of the pluripotent genes Sox2, Oct4, and Nanog. Simultaneously, CTGF also activates the transcription and phosphorylation of Smad3 through αVβ5 integrin, which is the central gene in chondrogenesis. Our study indicates that TRAP-positive monocyte-derived CTGF promotes bone healing by activating PSCs and directing lineage commitment and that targeting PSCs may be an effective strategy for preventing bone non-union.
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spelling pubmed-84768702021-09-29 Connective Tissue Growth Factor From Periosteal Tartrate Acid Phosphatase-Positive Monocytes Direct Skeletal Stem Cell Renewal and Fate During Bone Healing Bai, Yun Yu, Tao Deng, Jiezhong Yang, Yusheng Tan, Jiulin Dai, Qijie Zhang, Zehua Dong, Shiwu Xu, Jianzhong Front Cell Dev Biol Cell and Developmental Biology The periosteum is critical for bone healing. Studies have shown that the periosteum contains periosteal stem cells (PSCs) with multidirectional differentiation potential and self-renewal ability. PSCs are activated in early fracture healing and are committed to the chondrocyte lineage, which is the basis of callus formation. However, the mechanism by which PSCs are activated and committed to chondrocytes in bone regeneration remains unclear. Here, we show that tartrate acid phosphatase (TRAP)-positive monocytes secrete CTGF to activate PSCs during bone regeneration. The loss function of TRAP-positive monocytes identifies their specific role during bone healing. Then, the secreted CTGF promotes endochondral ossification and activates PSCs in mouse bone fracture models. The secreted CTGF enhances PSC renewal by upregulating the expression of multiple pluripotent genes. CTGF upregulates c-Jun expression through αVβ5 integrin. Then, c-Jun transcription activates the transcription of the pluripotent genes Sox2, Oct4, and Nanog. Simultaneously, CTGF also activates the transcription and phosphorylation of Smad3 through αVβ5 integrin, which is the central gene in chondrogenesis. Our study indicates that TRAP-positive monocyte-derived CTGF promotes bone healing by activating PSCs and directing lineage commitment and that targeting PSCs may be an effective strategy for preventing bone non-union. Frontiers Media S.A. 2021-09-14 /pmc/articles/PMC8476870/ /pubmed/34595178 http://dx.doi.org/10.3389/fcell.2021.730095 Text en Copyright © 2021 Bai, Yu, Deng, Yang, Tan, Dai, Zhang, Dong and Xu. https://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 Cell and Developmental Biology
Bai, Yun
Yu, Tao
Deng, Jiezhong
Yang, Yusheng
Tan, Jiulin
Dai, Qijie
Zhang, Zehua
Dong, Shiwu
Xu, Jianzhong
Connective Tissue Growth Factor From Periosteal Tartrate Acid Phosphatase-Positive Monocytes Direct Skeletal Stem Cell Renewal and Fate During Bone Healing
title Connective Tissue Growth Factor From Periosteal Tartrate Acid Phosphatase-Positive Monocytes Direct Skeletal Stem Cell Renewal and Fate During Bone Healing
title_full Connective Tissue Growth Factor From Periosteal Tartrate Acid Phosphatase-Positive Monocytes Direct Skeletal Stem Cell Renewal and Fate During Bone Healing
title_fullStr Connective Tissue Growth Factor From Periosteal Tartrate Acid Phosphatase-Positive Monocytes Direct Skeletal Stem Cell Renewal and Fate During Bone Healing
title_full_unstemmed Connective Tissue Growth Factor From Periosteal Tartrate Acid Phosphatase-Positive Monocytes Direct Skeletal Stem Cell Renewal and Fate During Bone Healing
title_short Connective Tissue Growth Factor From Periosteal Tartrate Acid Phosphatase-Positive Monocytes Direct Skeletal Stem Cell Renewal and Fate During Bone Healing
title_sort connective tissue growth factor from periosteal tartrate acid phosphatase-positive monocytes direct skeletal stem cell renewal and fate during bone healing
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476870/
https://www.ncbi.nlm.nih.gov/pubmed/34595178
http://dx.doi.org/10.3389/fcell.2021.730095
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