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

Yi Shi ¹Huaqiang Tao ²Xueyan Li ¹Liyuan Zhang ¹Chunhui Li ¹Wen Sun ¹Miao Chu ²Kai Chen ²Pengfei Zhu ²Qiang Wang ³Chengyong Gu ¹Liangliang Wang ⁴Xing Yang ⁵Yuefeng Hao⁵

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作者信息

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
折叠

Abstract

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 κ-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-a and IL-6 by inhibiting macrophage M1 phenotype.Mechanistically,KOR activation effectively suppresses the proinflammatory factor secretion of macrophages by inhibiting the translocation of NF-κB 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-κB 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.

Key words

synovial inflammation/macrophage polarization/κ-opioid receptor/osteoarthritis/NF-κB

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基金项目

Top Talent of Changzhou()

Program of Jiangsu Science and Technology Department(BK20211083)

Program of Jiangsu Science and Technology Department(BE2022737)

Suzhou Municipal Health Commission(SKJY2021115)

Jiangsu Medical Research Project(ZD2022021)

Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou(LCZX202003)

Program of Suzhou Health Commission(GSWS2020078)

Program of Suzhou Health Commission(GSWS2022002)

Program of Suzhou Health Commission(SZXK202111)

Suzhou Health Commission Science Education and Health Youth Project(KJXW2021040)

出版年

2024

生物化学与生物物理学报(英文版)

中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCDCSCD

影响因子：0.772

ISSN：1672-9145

参考文献量61

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