Study of the mechanism underlying hsa-miR338-3p downregulation to promote fibrosis of the synovial tissue in osteoarthritis patients

Song, Changzhi; Xu, Xiaohui; Wu, Ya; Ji, Biao; Zhou, Xigeng; Qin, Ling

doi:10.1007/s11033-018-4518-8

Cited by 17 publications

(23 citation statements)

References 30 publications

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“…Much evidence has shown that SF is one of the most important causes of joint stiffness, synovial hyperplasia, and limited function, which are common symptoms in moderate and severe OA; other evidence also confirmed that a higher SF score is correlated with lower scores for KL grade, which indicates that SF may be negatively associated with clinical symptoms of OA (22,23). This is because generalized pain is a major claim in OA patients, while independent joint stiffness does not occur very often.…”

Section: Clinical Status Of Synovial Fibrosismentioning

confidence: 97%

Synovial Fibrosis Involvement in Osteoarthritis

et al. 2021

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Bone changes have always been the focus of research on osteoarthritis, but the number of studies on synovitis has increased only over the last 10 years. Our current understanding is that the mechanism of osteoarthritis involves all the tissues that make up the joints, including nerve sprouting, pannus formation, and extracellular matrix environmental changes in the synovium. These factors together determine synovial fibrosis and may be closely associated with the clinical symptoms of pain, hyperalgesia, and stiffness in osteoarthritis. In this review, we summarize the consensus of clinical work, the potential pathological mechanisms, the possible therapeutic targets, and the available therapeutic strategies for synovial fibrosis in osteoarthritis to gain insight and provide a foundation for further study.

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Section: Clinical Status Of Synovial Fibrosismentioning

confidence: 97%

Synovial Fibrosis Involvement in Osteoarthritis

et al. 2021

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“…Type II collagen and aggrecan are the main ECM constituents of cartilage; MMP‐13 is the major type II collagen collagenase and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5 are the major aggrecanases. In cultured OA‐FLS, TGF‐β increases expression of TIMP1, TIMP2, MMP‐3, MMP‐8, MMP‐9, and MMP‐13 212,217‐220 . Cartilage wear products also increase MMP‐9, MMP‐10 and MMP‐13 in OA‐FLS in vitro 214 while TNF‐α and IL‐1β increase the expression of MMP‐1, MMP‐3, MMP‐9, MMP‐10, MMP‐13, or ADAMTS4 in healthy or OA‐FLS 214,229,230 .…”

Section: Inflammatory Fibroblast Dysfunctions: a Closer View Into The Synoviummentioning

confidence: 99%

The inflammatory speech of fibroblasts

Schuster

Rockel

Kapoor

et al. 2021

Immunological Reviews

100

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Successful tissue repair after injury requires the complex interplay of multiple cell types in different activation states in the context of an extracellular matrix (ECM) with changing compositional and mechanical properties. Normal repair occurs in a highly regulated sequence of overlapping phases comprising hemostasis, inflammation, proliferation, remodeling, and maturation. 1,2 With breached or leaky vasculature, platelets exit the bloodstream and create a provisional ECM that serves as initial scaffold for immune cells and growth factors.Mast cells are early responders, followed by neutrophils that fight invading microorganisms and create a local environment of cytokines and hypoxia that stimulate the recruitment and/or activation of macrophages. While clearing wound tissue from debris and dead cells,

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“…Its main pathological changes include extracellular matrix (ECM) accumulation and angiogenesis [11]. Numerous studies have confirmed the collagen deposition effect of transforming growth factor-β (TGF-β), while the collagen degradation inhibition is mainly due to the tissue inhibitor of metalloproteinase 1 (TIMP1) [12,13]. They both are crucial in regulating the ECM homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Agnuside Alleviates Synovitis and Fibrosis in Knee Osteoarthritis through the Inhibition of HIF-1α and NLRP3 Inflammasome

Zhang

et al. 2021

Mediators of Inflammation

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Increasing evidence has shown that NLRP3 inflammasome activation participates in chronic aseptic inflammation and is related to tissue fibrosis. Our last study also revealed the vital role of NLRP3 inflammasome, highly associated with tissue hypoxia, in the onset and development of knee osteoarthritis (KOA). In this study, we tried to find a possible benign intervention for that pathological process. Agnuside (AGN), a nontoxic, natural small molecule isolated from the extract of Vitex negundo L. (Verbenaceae), has been demonstrated to have antioxidation, anti-inflammatory, analgesia, and many other properties as an iridoid glycoside, although its specific target is still unclear. Therefore, we established MIA-induced KOA model rats and investigated the effects of AGN oral gavage on oxygen-containing state, NLRP3 inflammasome, synovitis, and fibrosis in KOA. Pimonidazole staining and HIF-1α immunohistochemical assay both showed that AGN at the oral dose of 6.25 mg/kg can effectively relieve local hypoxia in synovial tissue. Besides, we observed a decrease of HIF-1α, caspase-1, ASC, and NLRP3 after AGN intervention, both in the mRNA and protein levels. In addition, rats treated with the AGN showed less inflammatory reaction and fibrosis, not only in the expression of NLRP3, inflammasome downstream factors IL-1β and IL-18, and fibrosis markers TGF-β, TIMP1, and VEGF but also in the observation of HE staining, anatomical characteristics, Sirius Red staining, and type I collagen immunohistochemistry. Subsequently, we established LPS-induced models of fibroblast-like synoviocytes (FLSs) mimicking the inflammatory environment of KOA and activating NLRP3 inflammasome. FLSs treated with AGN (3 μM) resulted in a downregulation of HIF-1α and the components required for NLRP3 inflammasome activation. Meanwhile, the content of proinflammatory factors IL-1β and IL-18 in FLS supernatant was also reduced by AGN. In addition, both mRNA and protein levels of the fibrotic markers were significantly decreased after AGN management. To conclude, this study demonstrates that AGN alleviates synovitis and fibrosis in experimental KOA through the inhibition of HIF-1α accumulation and NLRP3 inflammasome activation. Additionally, not only does it reveal some novel targets for anti-inflammatory and antioxidant effects of AGN but also announces its potential value in treating KOA in humans.

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Study of the mechanism underlying hsa-miR338-3p downregulation to promote fibrosis of the synovial tissue in osteoarthritis patients

Cited by 17 publications

References 30 publications

Synovial Fibrosis Involvement in Osteoarthritis

Synovial Fibrosis Involvement in Osteoarthritis

The inflammatory speech of fibroblasts

Agnuside Alleviates Synovitis and Fibrosis in Knee Osteoarthritis through the Inhibition of HIF-1α and NLRP3 Inflammasome

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