Morroniside Attenuates Rheumatoid Arthritis by Inhibiting Rheumatoid Synoviocytes Invasion through the NF-κB/MMPs Pathway

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.

Keywords: invasion; morroniside; nuclear factor-B; rheumatoid arthritis; synoviocyte.