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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AAAS
2023
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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. |
format | Online Article Text |
id | pubmed-10202377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AAAS |
record_format | MEDLINE/PubMed |
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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