Endothelial PDGF-BB/PDGFR-βsignaling promotes osteoarthritis by enhancing angiogenesis-dependent abnormal subchondral bone formation  

作　　者：Zhuang Cui Hangtian Wu Ye Xiao Ting Xu Junjie Jia Hancheng Lin Rongmin Lin Kun Chen Yihuang Lin Kaiqun Li Xiaohu Wu Changjun Li Bin Yu 

机构地区：[1]Division of Orthopaedics and Traumatology,Department of Orthopaedics,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong,China [2]Guangdong Provincial Key Laboratory of Bone and Cartilage Regeneration Medicine,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong,China [3]Department of Endocrinology,Endocrinology Research Center,Xiangya Hospital of Central South University,Changsha,Hunan 410008,China [4]National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Changsha,Hunan 410008,China [5]Department of Sleep Medicine Center,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China

出　　处：《Bone Research》2022年第4期852-866,共15页骨研究（英文版）

基　　金：This study was supported by the Natural Science Foundation of Guangdong Province,China(2019A1515011614 to ZC);the Science and Technology Program of Guangzhou(202002030483 to ZC);the National Natural Science Foundation of China(81601942 to ZC and 81830079 to BY);the Outstanding Youths Development Scheme of Southern Medical University(2021YQPY008 to ZC);the National Key R&D Program of China(2019YFA0111900 to CL).

摘　　要：The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis(OA)remain unknown.No pharmacological intervention can currently prevent the progression of osteoarthritis.Accumulating evidence has shown that subchondral bone deterioration is a primary trigger for overlying cartilage degeneration.We previously found that H-type vessels modulate aberrant subchondral bone formation during the pathogenesis of OA.However,the mechanism responsible for the elevation of H-type vessels in OA is still unclear.Here,we found that PDGFR-βexpression,predominantly in the CD31^(hi)Emcn^(hi) endothelium,was substantially elevated in subchondral bones from OA patients and rodent OA models.A mouse model of OA with deletion of PDGFR-βin endothelial cells(ECs)exhibited fewer H-type vessels,ameliorated subchondral bone deterioration and alleviated overlying cartilage degeneration.Endothelial PDGFR-βpromotes angiogenesis through the formation of the PDGFR-β/talin1/FAK complex.Notably,endothelium-specific inhibition of PDGFR-βby local injection of AAV9 in subchondral bone effectively attenuated the pathogenesis of OA compared with that of the vehicle-treated controls.Based on the results from this study,targeting PDGFR-βis a novel and promising approach for the prevention or early treatment of OA.

关 键 词：DEGENERATION OSTEOARTHRITIS ANGIOGENESIS 

分 类 号：R684.3[医药卫生—骨科学]