Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis
Objectives: Synovitis plays an important role in knee osteoarthritis (KOA) pain. The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in fibroblast-like synoviocytes (FLSs) promotes KOA development. In this study, we aimed to investigate whether vanillic acid (VA), a monomer derive...
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Frontiers Media S.A.
2021-02-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.599022/full |
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author | Zhenyuan Ma Zhenyuan Ma Zhenyuan Ma Zhengquan Huang Zhengquan Huang Li Zhang Li Zhang Li Zhang Xiaochen Li Xiaochen Li Xiaochen Li Bo Xu Bo Xu Bo Xu Yancheng Xiao Yancheng Xiao Yancheng Xiao Xiaoqing Shi Xiaoqing Shi Haosheng Zhang Haosheng Zhang Haosheng Zhang Taiyang Liao Taiyang Liao Taiyang Liao Peimin Wang Peimin Wang |
author_facet | Zhenyuan Ma Zhenyuan Ma Zhenyuan Ma Zhengquan Huang Zhengquan Huang Li Zhang Li Zhang Li Zhang Xiaochen Li Xiaochen Li Xiaochen Li Bo Xu Bo Xu Bo Xu Yancheng Xiao Yancheng Xiao Yancheng Xiao Xiaoqing Shi Xiaoqing Shi Haosheng Zhang Haosheng Zhang Haosheng Zhang Taiyang Liao Taiyang Liao Taiyang Liao Peimin Wang Peimin Wang |
author_sort | Zhenyuan Ma |
collection | DOAJ |
description | Objectives: Synovitis plays an important role in knee osteoarthritis (KOA) pain. The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in fibroblast-like synoviocytes (FLSs) promotes KOA development. In this study, we aimed to investigate whether vanillic acid (VA), a monomer derived from Chinese herbal medicines, could target NLRP3 inflammasome-related synovitis to reduce pain.Methods: Rats in the KOA and KOA + VA groups were injected with monosodium iodoacetate (MIA) in the knee to induce KOA. From day 14, the KOA + VA group was given VA at 30 mg/kg every day via gastric intubation. FLSs were collected from the synovial tissues. We examined both the protein and gene expression of caspase-1, apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), NLRP3, components of the NLRP3 inflammasome, and interleukin-1β (IL-1β) and IL-18 in vivo and in vitro.Results: The upregulation of caspase-1, ASC, and NLRP3 in the KOA model were reduced by VA. VA also lowered the level of IL-1β and IL-18 in the KOA model. In addition, VA relieved pain-related behavior of KOA model rats and downregulated the pain mediators CGRP, NGF, and TrkA in FLSs. Interestingly, we also observed reduced synovial fibrosis in the animal experiments.Conclusion: Our research showed that VA reduces synovitis and pain-related behaviors in a rat model of KOA, which provides the basis for further investigations into the potential therapeutic impact of VA in KOA. |
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spelling | doaj.art-1bd3d57b19834c98baa4e3bd388426b72022-12-21T22:24:29ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-02-011110.3389/fphar.2020.599022599022Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related SynovitisZhenyuan Ma0Zhenyuan Ma1Zhenyuan Ma2Zhengquan Huang3Zhengquan Huang4Li Zhang5Li Zhang6Li Zhang7Xiaochen Li8Xiaochen Li9Xiaochen Li10Bo Xu11Bo Xu12Bo Xu13Yancheng Xiao14Yancheng Xiao15Yancheng Xiao16Xiaoqing Shi17Xiaoqing Shi18Haosheng Zhang19Haosheng Zhang20Haosheng Zhang21Taiyang Liao22Taiyang Liao23Taiyang Liao24Peimin Wang25Peimin Wang26Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaKey Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaKey Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaKey Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaKey Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaKey Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaKey Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaKey Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaObjectives: Synovitis plays an important role in knee osteoarthritis (KOA) pain. The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in fibroblast-like synoviocytes (FLSs) promotes KOA development. In this study, we aimed to investigate whether vanillic acid (VA), a monomer derived from Chinese herbal medicines, could target NLRP3 inflammasome-related synovitis to reduce pain.Methods: Rats in the KOA and KOA + VA groups were injected with monosodium iodoacetate (MIA) in the knee to induce KOA. From day 14, the KOA + VA group was given VA at 30 mg/kg every day via gastric intubation. FLSs were collected from the synovial tissues. We examined both the protein and gene expression of caspase-1, apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), NLRP3, components of the NLRP3 inflammasome, and interleukin-1β (IL-1β) and IL-18 in vivo and in vitro.Results: The upregulation of caspase-1, ASC, and NLRP3 in the KOA model were reduced by VA. VA also lowered the level of IL-1β and IL-18 in the KOA model. In addition, VA relieved pain-related behavior of KOA model rats and downregulated the pain mediators CGRP, NGF, and TrkA in FLSs. Interestingly, we also observed reduced synovial fibrosis in the animal experiments.Conclusion: Our research showed that VA reduces synovitis and pain-related behaviors in a rat model of KOA, which provides the basis for further investigations into the potential therapeutic impact of VA in KOA.https://www.frontiersin.org/articles/10.3389/fphar.2020.599022/fullvanillic acidknee osteoarthritissynovial inflammationNLRP3 inflammasomepain 3 |
spellingShingle | Zhenyuan Ma Zhenyuan Ma Zhenyuan Ma Zhengquan Huang Zhengquan Huang Li Zhang Li Zhang Li Zhang Xiaochen Li Xiaochen Li Xiaochen Li Bo Xu Bo Xu Bo Xu Yancheng Xiao Yancheng Xiao Yancheng Xiao Xiaoqing Shi Xiaoqing Shi Haosheng Zhang Haosheng Zhang Haosheng Zhang Taiyang Liao Taiyang Liao Taiyang Liao Peimin Wang Peimin Wang Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis Frontiers in Pharmacology vanillic acid knee osteoarthritis synovial inflammation NLRP3 inflammasome pain 3 |
title | Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis |
title_full | Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis |
title_fullStr | Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis |
title_full_unstemmed | Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis |
title_short | Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis |
title_sort | vanillic acid reduces pain related behavior in knee osteoarthritis rats through the inhibition of nlrp3 inflammasome related synovitis |
topic | vanillic acid knee osteoarthritis synovial inflammation NLRP3 inflammasome pain 3 |
url | https://www.frontiersin.org/articles/10.3389/fphar.2020.599022/full |
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