Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway
Osteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor pote...
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/12/2315 |
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| author | Heng Sun Ziying Sun Xingquan Xu Zhongyang Lv Jiawei Li Rui Wu Yuxiang Fei Guihua Tan Zizheng Liu Yuan Liu Dongquan Shi |
| author_facet | Heng Sun Ziying Sun Xingquan Xu Zhongyang Lv Jiawei Li Rui Wu Yuxiang Fei Guihua Tan Zizheng Liu Yuan Liu Dongquan Shi |
| author_sort | Heng Sun |
| collection | DOAJ |
| description | Osteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor potential channel subfamily V member 4), as an ion channel, plays a pivotal role in oxidative stress and inflammation. In this study, we investigated the role of TRPV4 in OA progression and M1 macrophage polarization. Male adult Sprague–Dawley (SD) rats underwent a medial meniscus radial transection operation to create an OA model in vivo and RAW 264.7 cells were intervened with 100 ng/mL LPS (lipopolysaccharide) to induce M1-polarized macrophages in vitro. We demonstrated that the infiltration of M1 synovial macrophages and the expression of TRPV4 were increased significantly in OA synovium. In addition, intra-articular injection of HC067074 (a specific inhibitor of TRPV4) alleviated the progression of rat OA and significantly decreased synovial macrophage M1 polarization. Further mechanisms suggested that ROS production by M1 macrophages was decreased after TRPV4 inhibition. In addition, NLRP3 (pyrin domain containing protein 3) as a downstream effector of ROS in M1-polarized macrophage, was significantly suppressed following TRPV4 inhibition. In conclusion, this study discovered that inhibition of TRPV4 delays OA progression by inhibiting M1 synovial macrophage polarization through the ROS/NLRP3 pathway. |
| first_indexed | 2024-03-09T17:24:18Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T17:24:18Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b01c423058e549198aa4387dace408da2023-11-24T12:55:56ZengMDPI AGAntioxidants2076-39212022-11-011112231510.3390/antiox11122315Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling PathwayHeng Sun0Ziying Sun1Xingquan Xu2Zhongyang Lv3Jiawei Li4Rui Wu5Yuxiang Fei6Guihua Tan7Zizheng Liu8Yuan Liu9Dongquan Shi10State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, ChinaOsteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor potential channel subfamily V member 4), as an ion channel, plays a pivotal role in oxidative stress and inflammation. In this study, we investigated the role of TRPV4 in OA progression and M1 macrophage polarization. Male adult Sprague–Dawley (SD) rats underwent a medial meniscus radial transection operation to create an OA model in vivo and RAW 264.7 cells were intervened with 100 ng/mL LPS (lipopolysaccharide) to induce M1-polarized macrophages in vitro. We demonstrated that the infiltration of M1 synovial macrophages and the expression of TRPV4 were increased significantly in OA synovium. In addition, intra-articular injection of HC067074 (a specific inhibitor of TRPV4) alleviated the progression of rat OA and significantly decreased synovial macrophage M1 polarization. Further mechanisms suggested that ROS production by M1 macrophages was decreased after TRPV4 inhibition. In addition, NLRP3 (pyrin domain containing protein 3) as a downstream effector of ROS in M1-polarized macrophage, was significantly suppressed following TRPV4 inhibition. In conclusion, this study discovered that inhibition of TRPV4 delays OA progression by inhibiting M1 synovial macrophage polarization through the ROS/NLRP3 pathway.https://www.mdpi.com/2076-3921/11/12/2315osteoarthritis (OA)TRPV4M1 macrophage polarizationNLRP3reactive oxygen species (ROS) |
| spellingShingle | Heng Sun Ziying Sun Xingquan Xu Zhongyang Lv Jiawei Li Rui Wu Yuxiang Fei Guihua Tan Zizheng Liu Yuan Liu Dongquan Shi Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway Antioxidants osteoarthritis (OA) TRPV4 M1 macrophage polarization NLRP3 reactive oxygen species (ROS) |
| title | Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway |
| title_full | Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway |
| title_fullStr | Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway |
| title_full_unstemmed | Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway |
| title_short | Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway |
| title_sort | blocking trpv4 ameliorates osteoarthritis by inhibiting m1 macrophage polarization via the ros nlrp3 signaling pathway |
| topic | osteoarthritis (OA) TRPV4 M1 macrophage polarization NLRP3 reactive oxygen species (ROS) |
| url | https://www.mdpi.com/2076-3921/11/12/2315 |
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