The emerging role of fibroblast‐like synoviocytes‐mediated synovitis in osteoarthritis: An update

Han, Dafei; Fang, Yingying; Tan, Xiaosheng; Jiang, Hongmei; Gong, Xun; Wang, Xinming; Hong, Wenming; Tu, Jiajie; Wei, Wei

doi:10.1111/jcmm.15669

Cited by 71 publications

(61 citation statements)

References 116 publications

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“…OA is a complex chronic disease and synovitis plays a prominent role in OA pathogenesis [32]. The NLRP3 in ammasome is also known to be associated with synovitis [33].…”

Section: Discussionmentioning

confidence: 99%

Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

Wang

Mobasheri

Zhang

et al. 2021

Preprint

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ObjectiveNLRP3 inflammasome may play a key role in OA pathogenesis. Stromal cell-derived factor-1 (SDF-1) is a homeostatic CXC chemokine. Since the role of SDF-1 in OA has not been explored, this study aimed to examine the effect of SDF-1 on NLRP3 inflammasome and pyroptosis in synoviocytes from OA joints.Materials and MethodsHuman synovium was obtained from OA patients for isolation of primary synoviocytes and a murine model of collagen-induced OA was established for testing intra-articular injections of SDF-1. Immunoblotting assays were used to examine the effects and underlying mechanism of action of SDF-1 on NLRP3 inflammasome and synoviocyte pyroptosis in synoviocytes. Inhibitors of AMPK and PI3K-mTOR were utilized to investigate the key signaling pathways involved in SDF-1-mediated OA inflammasome formation and pyroptosis.ResultsSynoviocytes from OA joints exhibited significantly higher expression of NLRP3 inflammasome and biomarkers of synoviocyte pyroptosis relative to healthy individuals. This was confirmed in the collagen-induced OA model, where OA synoviocytes had a significantly lower SDF-1 expression than healthy ones. SDF-1 treatment in synoviocytes of OA patients and collagen-induced OA led to significant downregulation in the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers. Inhibition of the AMPK signaling pathway significantly suppressed the inhibitory effect of SDF-1 on NLRP3 inflammasome expression of OA synoviocytes. However, blocking the SDF-1-activated PI3K-mTOR signaling pathway could still suppress the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers.ConclusionsSDF-1 ameliorates NLRP3 inflammasome and pyroptosis in OA synoviocytes through activation of the AMPK signaling pathway. Therefore, SDF-1 may be a novel therapeutic target for OA.

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“…OA is a complex chronic disease and synovitis plays a prominent role in OA pathogenesis [32]. The NLRP3 in ammasome is also known to be associated with synovitis [33].…”

Section: Discussionmentioning

confidence: 99%

Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

Wang

Mobasheri

Zhang

et al. 2021

Preprint

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“…Osteoarthritis (OA) is a highly prevalent joint disorder with whole-joint damage and dysfunction, mainly presented in aged population, leading to chronic pain, joint stiffness, and severe physical disability [ 1 , 2 ]. It is characterized by the loss of articular cartilage in addition to other joint disruption, including subchondral bone remodeling, osteophyte formation, synovium inflammation and meniscal damage [ 3 , 4 ]. Present OA management is widely divided into nonpharmacological, pharmacological, and surgical treatments [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression

et al. 2021

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Background: Osteoarthritis (OA), a disease with whole-joint damage and dysfunction, is the leading cause of disability worldwide. The progressive loss of hyaline cartilage extracellular matrix (ECM) is considered as its hallmark, but its exact pathogenesis needs to be further clarified. MicroRNA(miRNA) contributes to OA pathology and may help to identify novel biomarkers and therapies against OA. Here we identified miR-214À3p as an important regulator of OA. Methods: qRT-PCR and in situ hybridization were used to detect the expression level of miR-214À3p. The function of miR-214À3p in OA, as well as the interaction between miR-214À3p and its downstream mRNA target (IKBKB), was evaluated by western blotting, immunofluorescence, qRT-PCR and luciferase assay. Mice models were introduced to examine the function and mechanism of miR-214À3p in OA in vivo. Findings: In our study, we found that miR-214À3p, while being down-regulated in inflamed chondrocytes and OA cartilage, regulated ECM metabolism and cell apoptosis in the cartilage. Mechanically, the protective effect of miR-214À3p downregulated the IKK-b expression and led to the dysfunction of NF-kB signaling pathway. Furthermore, intra-articular injection of miR-214À3p antagomir in mice joints triggered spontaneous cartilage loss while miRNA-214À3p agomir alleviated OA in the experimental mouse models. Interpretation: Decreased miR-214À3p activates the NF-kB signaling pathway and aggravates OA development through targeting IKKb, suggesting miR-214À3p may be a novel therapeutic target for OA.

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“…OA is a complex chronic disease and synovitis plays a prominent role in OA pathogenesis (Han et al 2020). The NLRP3 inflammasome is also known to be associated with synovitis (Clavijo-Cornejo et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Exogenous stromal cell-derived factor-1 (SDF-1) suppresses the NLRP3 inflammasome and inhibits pyroptosis in synoviocytes from osteoarthritic joints via activation of the AMPK signaling pathway

et al. 2021

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Objective NLRP3 inflammasome may play a key role in OA pathogenesis. Stromal cell-derived factor-1 (SDF-1) is a homeostatic CXC chemokine. Since the role of SDF-1 in OA has not been explored, this study aimed to examine the effect of SDF-1 on NLRP3 inflammasome and pyroptosis in synoviocytes from OA joints. Materials and methods Human synovium was obtained from OA patients for isolation of primary synoviocytes and a murine model of collagenase-induced OA was established for testing intra-articular injections of SDF-1. Immunoblotting assays were used to examine the effects and underlying mechanism of action of SDF-1 on NLRP3 inflammasome and synoviocyte pyroptosis in synoviocytes. Inhibitors of AMPK and PI3K–mTOR were utilized to investigate the key signaling pathways involved in SDF-1-mediated OA inflammasome formation and pyroptosis. Results Synoviocytes from OA joints exhibited significantly higher expression of NLRP3 inflammasome and biomarkers of synoviocyte pyroptosis relative to healthy individuals. This was confirmed in the collagenase-induced OA model, where OA synoviocytes had a significantly lower SDF-1 expression than healthy ones. SDF-1 treatment in synoviocytes of OA patients and collagenase-induced OA led to significant downregulation in the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers. Inhibition of the AMPK signaling pathway significantly suppressed the inhibitory effect of SDF-1 on NLRP3 inflammasome expression of OA synoviocytes. However, blocking the SDF-1-activated PI3K–mTOR signaling pathway could still suppress the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers. Conclusions SDF-1 ameliorates NLRP3 inflammasome and pyroptosis in OA synoviocytes through activation of the AMPK signaling pathway. Therefore, SDF-1 may be a novel therapeutic target for OA.

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The emerging role of fibroblast‐like synoviocytes‐mediated synovitis in osteoarthritis: An update

Cited by 71 publications

References 116 publications

Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression

Exogenous stromal cell-derived factor-1 (SDF-1) suppresses the NLRP3 inflammasome and inhibits pyroptosis in synoviocytes from osteoarthritic joints via activation of the AMPK signaling pathway

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