{"title":"Morroniside Attenuates Rheumatoid Arthritis by Inhibiting Rheumatoid Synoviocytes Invasion through the NF-κB/MMPs Pathway.","authors":"Yan Wang, Ruili Yin, Xin Li, Baoyu Zhang, Yuan Wang, Lijie Zhang, Yanan Cheng, Dong Zhao","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Morroniside (MOR) has been reported to ameliorate inflammation in cardiovascular and cerebrovascular disease; however, its impact and mechanism on rheumatoid arthritis (RA) remains unclear. This study aimed to investigate the beneficial role of morroniside in treating RA and explore the anti-invasive mechanism of morroniside on joint destruction.</p><p><strong>Methods: </strong><i>In vitro</i> (using primary rat articular fibroblast-like synoviocytes (FLSs)) a wound healing assay was used to detect the migration of primary rat FLSs. Quantitative RT-PCR was used to measure the transcription of matrix metalloproteinase (MMP) MMP2 and MMP9. Western blot was used to measure the expression of MMP2, MMP9, p65, phosphorylated-p65 (p-p65), inhibitor of nuclear factor (NF)-[Formula: see text]B<i>α</i> (I[Formula: see text]B<i>α</i>), I[Formula: see text]B kinase <i>α</i>/β (IKK<i>α</i>/β), and phosphorylated-IKK<i>α</i>/β. Immunofluorescence assay was used to measure the nuclear translocation of p65. <i>In vivo</i> (using rats with collagen-induced arthritis), the joint histopathological changes were detected by routine hematoxylin and eosin. Immunohistochemistry assay was used to measure the expression MMP2 and MMP9.</p><p><strong>Results: </strong>Morroniside diminished tumor necrosis factor (TNF)<i>α</i>-stimulated migration of primary rat articular FLSs. Morroniside also attenuated RA-FLSs invasion into joint and joint destruction in rats with collagen-induced arthritis (CIA). Further analysis revealed that morroniside inhibited the overexpression of matrix metalloproteinase MMP2 and MMP9 in TNF<i>α</i>-stimulated primary rat articular FLSs and joints of CIA rats. Mechanistically, morroniside suppressed the activation of I[Formula: see text]B kinase <i>α</i>/β, which resulted in elevated levels of the inhibitor of nuclear factor (NF)-[Formula: see text]B.</p><p><strong>Conclusion: </strong>The present study suggested that morroniside can prevent joint destruction by suppressing the activation of the NF-[Formula: see text]B/MMPs pathway, thereby preventing FLSs invasion.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"54 5","pages":"604-617"},"PeriodicalIF":1.1000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of clinical and laboratory science","FirstCategoryId":"3","ListUrlMain":"","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Morroniside (MOR) has been reported to ameliorate inflammation in cardiovascular and cerebrovascular disease; however, its impact and mechanism on rheumatoid arthritis (RA) remains unclear. This study aimed to investigate the beneficial role of morroniside in treating RA and explore the anti-invasive mechanism of morroniside on joint destruction.
Methods: In vitro (using primary rat articular fibroblast-like synoviocytes (FLSs)) a wound healing assay was used to detect the migration of primary rat FLSs. Quantitative RT-PCR was used to measure the transcription of matrix metalloproteinase (MMP) MMP2 and MMP9. Western blot was used to measure the expression of MMP2, MMP9, p65, phosphorylated-p65 (p-p65), inhibitor of nuclear factor (NF)-[Formula: see text]Bα (I[Formula: see text]Bα), I[Formula: see text]B kinase α/β (IKKα/β), and phosphorylated-IKKα/β. Immunofluorescence assay was used to measure the nuclear translocation of p65. In vivo (using rats with collagen-induced arthritis), the joint histopathological changes were detected by routine hematoxylin and eosin. Immunohistochemistry assay was used to measure the expression MMP2 and MMP9.
Results: Morroniside diminished tumor necrosis factor (TNF)α-stimulated migration of primary rat articular FLSs. Morroniside also attenuated RA-FLSs invasion into joint and joint destruction in rats with collagen-induced arthritis (CIA). Further analysis revealed that morroniside inhibited the overexpression of matrix metalloproteinase MMP2 and MMP9 in TNFα-stimulated primary rat articular FLSs and joints of CIA rats. Mechanistically, morroniside suppressed the activation of I[Formula: see text]B kinase α/β, which resulted in elevated levels of the inhibitor of nuclear factor (NF)-[Formula: see text]B.
Conclusion: The present study suggested that morroniside can prevent joint destruction by suppressing the activation of the NF-[Formula: see text]B/MMPs pathway, thereby preventing FLSs invasion.
期刊介绍:
The Annals of Clinical & Laboratory Science
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