دورية أكاديمية
Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway
| العنوان: | Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway |
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| المؤلفون: | Heng Sun, Ziying Sun, Xingquan Xu, Zhongyang Lv, Jiawei Li, Rui Wu, Yuxiang Fei, Guihua Tan, Zizheng Liu, Yuan Liu, Dongquan Shi |
| المصدر: | Antioxidants, Vol 11, Iss 12, p 2315 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | osteoarthritis (OA), TRPV4, M1 macrophage polarization, NLRP3, reactive oxygen species (ROS), Therapeutics. Pharmacology, RM1-950 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 11122315 2076-3921 |
| Relation: | https://www.mdpi.com/2076-3921/11/12/2315; https://doaj.org/toc/2076-3921 |
| DOI: | 10.3390/antiox11122315 |
| URL الوصول: | https://doaj.org/article/b01c423058e549198aa4387dace408da |
| رقم الأكسشن: | edsdoj.b01c423058e549198aa4387dace408da |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 11122315 20763921 |
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| DOI: | 10.3390/antiox11122315 |