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

作　　者：Fangqian Wang Yuxiao Ye Zengjie Zhang Wangsiyuan Teng Hangxiang Sun Xupeng Chai Xingzhi Zhou Jiayu Chen Haochen Mou Yinwang Eloy Xiaoqiang Jin Liang Chen Zhenxuan Shao Yan Wu Yue Shen An Liu Peng Lin Jianwei Wang Xiaohua Yu Zhaoming Ye 

机构地区：[1]Department of Orthopedic Surgery,the Second Affiliated Hospital,Zhejang University School of Medicine,Hangzhou City,Zhejiang Province,PR China [2]Orthopedics Research Institute of Zhejang University,Hangzhou City,Zhejiang Province,PR China [3]Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province,Hangzhou City,Zhejiang Province,PR China [4]School of Material Science and Engineering,University of New South Wales,Sydney 2052,Australia

出　　处：《Research》2024年第1期33-48,共16页研究（英文）

基　　金：supported by the National Key Research and Development Projects(2018YFC1105400);the National Natural Science Foundation of China(81872173,82072959,and 31870959);the Zhejiang Provincial Natural Science Foundation(GF22H068757);the Zhejiang Undergraduate Talent Project(2021R401214).

摘　　要：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-βpathway 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-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked 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-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.

关 键 词：HEALING sized implantation 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]