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Morroniside Attenuates Rheumatoid Arthritis by Inhibiting Rheumatoid Synoviocytes Invasion through the NF-κB/MMPs
Yan Wang1,2, Ruili Yin1,2, Xin Li1,2
1Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Tongzhou District, Beijing, China.
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.
Insights
Morroniside (MOR) effectively inhibits rheumatoid arthritis (RA) joint destruction by preventing fibroblast-like synoviocyte (FLS) invasion. It suppresses the NF-κB/MMPs pathway, offering a potential therapeutic strategy for RA.
Area of Science:
- Pharmacology
- Immunology
- Rheumatology
Background:
- Morroniside (MOR) shows anti-inflammatory effects in cardiovascular and cerebrovascular diseases.
- The mechanism of MOR in rheumatoid arthritis (RA) and its effect on joint destruction are not well understood.
Purpose of the Study:
- To investigate the therapeutic potential of morroniside in rheumatoid arthritis (RA).
- To explore the anti-invasive mechanism of morroniside on joint destruction in RA.
Main Methods:
- In vitro studies used primary rat articular fibroblast-like synoviocytes (FLSs) to assess migration and matrix metalloproteinase (MMP) expression (MMP2, MMP9).
- Western blot and immunofluorescence were employed to analyze the NF-κB signaling pathway components.
- In vivo studies utilized a collagen-induced arthritis (CIA) rat model to evaluate joint histopathology and MMP expression.
Main Results:
- Morroniside reduced TNFα-stimulated FLS migration and attenuated joint invasion and destruction in CIA rats.
- MOR inhibited the overexpression of MMP2 and MMP9 in both stimulated FLSs and CIA rat joints.
- Mechanistically, morroniside suppressed IKKα/β activation, leading to increased levels of IκBα and inhibition of NF-κB.
Conclusions:
- Morroniside prevents joint destruction in RA by inhibiting FLS invasion.
- The anti-arthritic effect of MOR is mediated through the suppression of the NF-κB/MMPs pathway.
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