Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis  

作　　者：Miao CHU Guangdong CHEN Kai CHEN Pengfei ZHU Zhen WANG Zhonglai QIAN Huaqiang TAO Yaozeng XU Dechun GENG 

机构地区：[1]Department of Orthopedics,the First Affiliated Hospital of Soochow University,Suzhou 215006,China [2]Department of Orthopedics,Yixing People’s Hospital,Yixing 214200,China [3]Department of Orthopedics,Hai’an People’s Hospital,Hai’an 226600,China [4]Department of Orthopedics,Suzhou Kowloon Hospital,Shanghai Jiao Tong University School of Medicine,Suzhou 215028,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第6期513-528,共16页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China(Nos.82272157,82072425,and 82072498);the Natural Science Foundation of Jiangsu Province(No.BE2021650);the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,the Program of Suzhou Health Commission(Nos.GSWS2022002 and GSWS2020121);the Jiangsu Medical Research Project(No.ZD2022014);the National and Local Engineering Laboratory of New Functional Polymer Materials(No.SDGC2205);the Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou(No.LCZX202003),China.

摘　　要：Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

关 键 词：OSTEOCLAST Oxidative stress Osteoarthritis(OA) Heme oxygenase 1(HMOX1) CARNOSOL 

分 类 号：S567.31[农业科学—中草药栽培]