2. Academic Validation
  3. TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway

TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway

  • Cell Death Dis. 2021 May 18;12(6):504. doi: 10.1038/s41419-021-03792-8.
Zhongyang Lv  # 1 2,  Xingquan Xu  # 1 2,  Ziying Sun 1 2,  Yannick Xiaofan Yang 1 3,  Hu Guo 1 2,  Jiawei Li 1 2,  Kuoyang Sun 1 2,  Rui Wu 1 2,  Jia Xu 1 3,  Qing Jiang 1 2,  Shiro Ikegawa 1 4,  Dongquan Shi 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, People's Republic of China.
  • 2 Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing, 210093, Jiangsu, People's Republic of China.
  • 3 Drum Tower of Clinical Medicine, Nanjing Medical University, Nanjing, 210008, Jiangsu, People's Republic of China.
  • 4 Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Science (IMS, RIKEN), Tokyo, 108-8639, Japan.
  • 5 State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, People's Republic of China. shidongquan@nju.edu.cn.
  • 6 Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing, 210093, Jiangsu, People's Republic of China. shidongquan@nju.edu.cn.
  • # Contributed equally.
PMID: 34006826 DOI: 10.1038/s41419-021-03792-8
Abstract

Osteoarthritis (OA) is the major course of joint deterioration, in which M1 macrophage-driven synovitis exacerbates the pathological process. However, precise therapies for M1 macrophage to decrease synovitis and attenuate OA progression have been scarcely proposed. Transient receptor potential vanilloid 1 (TRPV1) is a cation channel that has been implicated in pain perception and inflammation. In this study, we investigated the role of TRPV1 in the M1 macrophage polarization and pathogenesis of OA. We demonstrated that TRPV1 expression and M1 macrophage infiltration were simultaneously increased in both human and rat OA synovium. More than 90% of the infiltrated M1 macrophages expressed TRPV1. In the rat OA model, intra-articular injection of capsaicin (CPS), a specific TRPV1 agonist, significantly attenuated OA phenotypes, including joint swelling, synovitis, cartilage damage, and osteophyte formation. CPS treatment markedly reduced M1 macrophage infiltration in the synovium. Further mechanistic analyses showed that TRPV1-evoked CA2+ influx promoted the phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and facilitated the nuclear localization of nuclear factor-erythroid 2-related factor 2 (Nrf2), which ultimately resulted in the inhibition of M1 macrophage polarization. Taken together, our findings establish that TRPV1 attenuates the progression of OA by inhibiting M1 macrophage polarization in synovium via the CA2+/CaMKII/Nrf2 signaling pathway. These results highlight the effect of targeting TRPV1 for the development of a promising therapeutic strategy for OA.

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