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PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner

Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) pathway is conventionally considered as an important pathway to promote osteogenesis; however, recent study suggested its role during osteogenesis to be controversial. Regarding the differential functions...

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Autores principales: Wang, Fangqian, Ye, Yuxiao, Zhang, Zengjie, Teng, Wangsiyuan, Sun, Hangxiang, Chai, Xupeng, Zhou, Xingzhi, Chen, Jiayu, Mou, Haochen, Eloy, Yinwang, Jin, Xiaoqiang, Chen, Liang, Shao, Zhenxuan, Wu, Yan, Shen, Yue, Liu, An, Lin, Peng, Wang, Jianwei, Yu, Xiaohua, Ye, Zhaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAAS 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202377/
https://www.ncbi.nlm.nih.gov/pubmed/37223474
http://dx.doi.org/10.34133/research.0086
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author Wang, Fangqian
Ye, Yuxiao
Zhang, Zengjie
Teng, Wangsiyuan
Sun, Hangxiang
Chai, Xupeng
Zhou, Xingzhi
Chen, Jiayu
Mou, Haochen
Eloy, Yinwang
Jin, Xiaoqiang
Chen, Liang
Shao, Zhenxuan
Wu, Yan
Shen, Yue
Liu, An
Lin, Peng
Wang, Jianwei
Yu, Xiaohua
Ye, Zhaoming
author_facet Wang, Fangqian
Ye, Yuxiao
Zhang, Zengjie
Teng, Wangsiyuan
Sun, Hangxiang
Chai, Xupeng
Zhou, Xingzhi
Chen, Jiayu
Mou, Haochen
Eloy, Yinwang
Jin, Xiaoqiang
Chen, Liang
Shao, Zhenxuan
Wu, Yan
Shen, Yue
Liu, An
Lin, Peng
Wang, Jianwei
Yu, Xiaohua
Ye, Zhaoming
author_sort Wang, Fangqian
collection PubMed
description Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) pathway is conventionally considered as an important pathway to promote osteogenesis; however, recent study suggested its role during osteogenesis to be controversial. Regarding the differential functions of this pathway during 3 stages of bone healing, we hypothesized that temporal inhibition of PDGF-BB/PDGFR-β pathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells, toward osteogenic lineage, which leads to improved bone regeneration. We first validated that inhibition of PDGFR-β at late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts. This effect was also replicated in vivo by showing accelerated bone formation when block PDGFR-β pathway at late stage of critical bone defect healing mediated using biomaterials. Further, we found that such PDGFR-β inhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally. Mechanistically, timely inhibition of PDGFR-β blocked extracellular regulated protein kinase 1/2 pathway, which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis. This study offered updated understanding of the use of PDGFR-β pathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.
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spelling pubmed-102023772023-05-23 PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner Wang, Fangqian Ye, Yuxiao Zhang, Zengjie Teng, Wangsiyuan Sun, Hangxiang Chai, Xupeng Zhou, Xingzhi Chen, Jiayu Mou, Haochen Eloy, Yinwang Jin, Xiaoqiang Chen, Liang Shao, Zhenxuan Wu, Yan Shen, Yue Liu, An Lin, Peng Wang, Jianwei Yu, Xiaohua Ye, Zhaoming Research (Wash D C) Research Article Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) pathway is conventionally considered as an important pathway to promote osteogenesis; however, recent study suggested its role during osteogenesis to be controversial. Regarding the differential functions of this pathway during 3 stages of bone healing, we hypothesized that temporal inhibition of PDGF-BB/PDGFR-β pathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells, toward osteogenic lineage, which leads to improved bone regeneration. We first validated that inhibition of PDGFR-β at late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts. This effect was also replicated in vivo by showing accelerated bone formation when block PDGFR-β pathway at late stage of critical bone defect healing mediated using biomaterials. Further, we found that such PDGFR-β inhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally. Mechanistically, timely inhibition of PDGFR-β blocked extracellular regulated protein kinase 1/2 pathway, which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis. This study offered updated understanding of the use of PDGFR-β pathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair. AAAS 2023-05-05 /pmc/articles/PMC10202377/ /pubmed/37223474 http://dx.doi.org/10.34133/research.0086 Text en Copyright © 2023 Fangqian Wang et al. https://creativecommons.org/licenses/by/4.0/Exclusive licensee Science and Technology Review Publishing House. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Wang, Fangqian
Ye, Yuxiao
Zhang, Zengjie
Teng, Wangsiyuan
Sun, Hangxiang
Chai, Xupeng
Zhou, Xingzhi
Chen, Jiayu
Mou, Haochen
Eloy, Yinwang
Jin, Xiaoqiang
Chen, Liang
Shao, Zhenxuan
Wu, Yan
Shen, Yue
Liu, An
Lin, Peng
Wang, Jianwei
Yu, Xiaohua
Ye, Zhaoming
PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner
title PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner
title_full PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner
title_fullStr PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner
title_full_unstemmed PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner
title_short PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner
title_sort pdgfr in pdgf-bb/pdgfr signaling pathway does orchestrates osteogenesis in a temporal manner
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202377/
https://www.ncbi.nlm.nih.gov/pubmed/37223474
http://dx.doi.org/10.34133/research.0086
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