κ-Opioid receptor activation attenuates osteoarthritis synovitis by regulating macrophage polarization through the NF-κB pathway  

作　　者：Yi Shi Huaqiang Tao Xueyan Li Liyuan Zhang Chunhui Li Wen Sun Miao Chu Kai Chen Pengfei Zhu Qiang Wang Chengyong Gu Liangliang Wang Xing Yang Yuefeng Hao 

机构地区：[1]Anesthesiology Department,Suzhou Municipal Hospital(North District),Nanjing Medical University Affiliated Suzhou Hospital,Suzhou 215000,China [2]Department of Orthopedics,the First Affiliated Hospital of Soochow University,Suzhou 215000,China [3]Department of Orthopedics,Changshu Hospital Affiliated to Soochow University,First People’s Hospital of Changshu City,Changshu 215500,China [4]Department of Orthopedics,the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University,Changzhou 213000,China [5]Orthopedics and Sports Medicine Center,Suzhou Municipal Hospital,Nanjing Medical University Affiliated Suzhou Hospital,Suzhou 215000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第1期82-95,共14页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Top Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project,the Program of Jiangsu Science and Technology Department(Nos.BK20211083 and BE2022737);the Suzhou Municipal Health Commission(No.SKJY2021115);Jiangsu Medical Research Project(No.ZD2022021);the Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou(No.LCZX202003);the Program of Suzhou Health Commission(Nos.GSWS2020078,GSWS2022002,and SZXK202111);the Suzhou Health Commission Science Education and Health Youth Project(No.KJXW2021040).

摘　　要：Osteoarthritis(OA)is a prevalent and chronic joint disease that affects the aging population,causing pain and disability.Macrophages in synovium are important mediators of synovial inflammatory activity and pathological joint pain.Previous studies have demonstrated the significant involvement of k-opioid receptor(KOR)in the reg-ulation of pain and inflammation.Our study reveals a significant reduction in synovial KOR expression among patients and mice with OA.Here,we find that KOR activation effectively inhibits the expressions of the LPS-induced-inflammatory cytokines TNF-αand IL-6 by inhibiting macrophage M1 phenotype.Mechanistically,KOR activation effectively suppresses the proinflammatory factor secretion of macrophages by inhibiting the translocation of NF-kB into the nucleus.Our animal experiments reveal that activation of KOR effectively alleviates knee pain and prevents synovitis progression in OA mice.Consistently,KOR administration suppresses the expressions of M1 macrophage markers and the NF-kB pathway in the synovium of the knee.Collectively,our study suggests that targeting KOR may be a viable strategy for treating OA by inhibiting synovitis and improving joint pain in affected patients.

关 键 词：synovial inflammation macrophage polarization K-opioid receptor OSTEOARTHRITIS NF-KB 

分 类 号：R68[医药卫生—骨科学]