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...

Full description

Bibliographic Details
Main Authors: Zhenyuan Ma, Zhengquan Huang, Li Zhang, Xiaochen Li, Bo Xu, Yancheng Xiao, Xiaoqing Shi, Haosheng Zhang, Taiyang Liao, Peimin Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2020.599022/full
_version_ 1818615523448979456
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.
first_indexed 2024-12-16T16:35:16Z
format Article
id doaj.art-1bd3d57b19834c98baa4e3bd388426b7
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-12-16T16:35:16Z
publishDate 2021-02-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
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
work_keys_str_mv AT zhenyuanma vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT zhenyuanma vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT zhenyuanma vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT zhengquanhuang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT zhengquanhuang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT lizhang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT lizhang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT lizhang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT xiaochenli vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT xiaochenli vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT xiaochenli vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT boxu vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT boxu vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT boxu vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT yanchengxiao vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT yanchengxiao vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT yanchengxiao vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT xiaoqingshi vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT xiaoqingshi vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT haoshengzhang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT haoshengzhang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT haoshengzhang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT taiyangliao vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT taiyangliao vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT taiyangliao vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT peiminwang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis
AT peiminwang vanillicacidreducespainrelatedbehaviorinkneeosteoarthritisratsthroughtheinhibitionofnlrp3inflammasomerelatedsynovitis