scholarly journals Proteomic analysis of synovial tissue in rheumatoid arthritis, OLFM4 promotes fibroblast like synoviocytes proliferation in RA

2020 ◽  
Author(s):  
Xiaoyu Ren ◽  
Ke Xu ◽  
Jing Xu ◽  
Manman Geng ◽  
Chao Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Western Blotting ◽  
Protein Processing ◽  
Protein Profiles ◽  
Kegg Analysis ◽  
Unique Protein ◽  
On Line ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

Abstract Background To understand the roles of synovial tissue in rheumatoid arthritis (RA), we comprehensively investigated the protein profiles of synovial tissues in patients with RA and osteoarthritis (OA). Methods Protein were isolated from synovial tissues of 46 patients (22 with RA, 24with OA). Proteins were digested and labeled with TMT kit. All the peptide were send to LC-MS/MS analysis, and processed with Mascot and Proteome Discovery (version 1.4) search engines. All the protein data were analysis with Gene ontology (GO) and KEGG on line database. Four up-regulated protein were examined with western blotting and IHC. The RNAi were used for revealing the OLFM4 function in FLS. Results In total, over 500 proteins were identified as the different expression protein compared RA and OA synovia tissues, including 239 proteins were up-regulated in RA, and 271 proteins were up-regulated in OA. GO and KEGG analysis of the different expressed protein mostly identified as developmental processes and protein processing in ER. RT-qPCR, western blotting and IHC confirmed that there was a strong over expressed OLFM4 in RA synovia tissues. OLFM4 could be up-regulated under inflammatory stimulation, and participate in fibroblast like synoviocytes proliferation. Conclusion patients with RA possessed considerably different protein profiles of synovial tissues from with OA. The unique protein profiles of RA synovial tissues, such as the OLFM4 and MZB1 had been up-regulated compared to the OA, may reflect the pathophysiology of RA.

scholarly journals Knockdown of nrf2 Exacerbates TNF-α-Induced Proliferation and Invasion of Rheumatoid Arthritis Fibroblast-Like Synoviocytes through Activating JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yu Du ◽  
Qian Wang ◽  
Na Tian ◽  
Meng Lu ◽  
Xian-Long Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Western Blotting ◽  
Nuclear Translocation ◽  
Cell Counting ◽  
Related Factor ◽  
Jnk Pathway ◽  
Tnf Α ◽  
Synovial Tissues ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

Fibroblast-like synoviocytes (FLS) in the synovial tissue of rheumatoid arthritis (RA) exhibit over-proliferative and aggressive phenotypes, which participate in the pathophysiology of RA. In RA, little is known about the nonantioxidant effect of nuclear factor erythroid 2-related factor 2 (nrf2), the master regulator of redox homeostasis. In this study, we aimed to explore the expression and upstream regulatory factors of nrf2 and revealed its functions in modulating the proliferation and invasion in RA-FLS. FLS were isolated from RA and osteoarthritis patients. Expression of nrf2 in the synovial tissues and FLS was analyzed by immunohistochemistry, real-time PCR, Western blotting, and immunofluorescence staining. Cell proliferation was examined by Cell Counting Kit-8. Cell invasion was tested by transwell assay. Phosphorylation of JNK was determined by Western blotting. The results showed that nrf2 expression in the RA synovial tissues was upregulated. TNF-α promoted expression and nuclear translocation of nrf2 in RA-FLS and increased the intracellular reactive oxygen species (ROS) level. Nrf2 nuclear translocation was blocked by ROS inhibitor N-acetylcysteine. Both knockdown of nrf2 by siRNA and inhibition of nrf2 by ML385 significantly promoted the TNF-α-induced proliferation and invasion of RA-FLS. Activation of nrf2 by sulforaphane (SFN) profoundly inhibited the TNF-α-induced proliferation and invasion of RA-FLS. Knockdown of nrf2 also enhanced the TNF-α-induced matrix metalloproteinases (MMPs) expression and phosphorylation of JNK in RA-FLS. Proliferation and invasion of RA-FLS incubated with TNF-α and nrf2 siRNA were inhibited by pretreatment with JNK inhibitor SP600125. In conclusion, nrf2 is overexpressed in synovial tissues of RA patients, which may be promoted by TNF-α and ROS levels. Activation of nrf2 may suppress TNF-α-induced proliferation, invasion, and MMPs expression in RA-FLS by inhibiting JNK activation, indicating that nrf2 plays a protective role in relieving the severity of synovitis in RA. Our results might provide novel insights into the treatment of RA.

scholarly journals Differential inflammation-mediated function of prokineticin 2 in the synovial fibroblasts of patients with rheumatoid arthritis compared to osteoarthritis

2021 ◽  
Author(s):  
Kentaro Noda ◽  
Bianca Dufner ◽  
Haruyasu Ito ◽  
Ken Yoshida ◽  
Gianfranco Balboni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Sickness Behaviors ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

Abstract Prokineticin 2 (PK2) is a secreted protein involved in several pathological and physiological processes, including the regulation of inflammation, sickness behaviors, and the circadian rhythm. Recently, it was reported that PK2 is associated with the pathogenesis of collagen-induced arthritis in mice. However, whether PK2 influences the pathogenesis of rheumatoid arthritis (RA) or osteoarthritis (OA) remains unknown. In this study, we collected synovial tissue, plasma, synovial fluid, and fibroblast-like synoviocytes (FLS) from RA and OA patients to analyze the role of PK2 using immunohistochemistry, ELISAs, and tissue superfusion studies. PK2 and its receptors prokineticin receptor (PKR) 1 and 2 were expressed in RA and OA synovial tissues. PKR1 expression in RA synovial tissue was downregulated compared with OA synovial tissue. The PK2 concentration was higher in RA synovial fluid than in OA synovial fluid but similar between RA and OA plasma. PK2 suppressed the production of IL-6 from TNFα-prestimulated OA-FLS, and this effect was attenuated in TNFα-prestimulated RA-FLS. This phenomenon was accompanied by the upregulation of PKR1 in OA-FLS and the downregulation of PK2 and PKR1 in RA-FLS. This study provides a new model to explain some aspects underlying the chronicity of inflammation in RA.

scholarly journals Intervening the up-regulated SLC7A5 could mitigate the inflammatory mediator by mTOR-P70S6K signal in rheumatoid arthritis synoviocytes.

2020 ◽  
Author(s):  
Jing Xu ◽  
Congshan Jiang ◽  
Yongsong Cai ◽  
Yuanxu Guo ◽  
Xipeng Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Expression ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Inflammatory Mediator ◽  
Protein Translation ◽  
Rheumatoid Arthritis Synoviocytes ◽  
Synovial Tissues ◽  
Signaling Activation ◽  
Fibroblast Like Synoviocytes

Abstract Objective The increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability are found in rheumatoid arthritis (RA). This study aimed to observe the effects of SLC7A5 (amino acid transporter) on synoviocytes of RA patients and pinpoint the underlying molecular mechanisms. Methods Synovial tissues were collected from OA and RA patients. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues from RA patients. SLC7A5 expression was evaluated by using RT-qPCR, immunofluorescence and Western blotting. Matrix metalloproteinases (MMPs) expression was evaluated by using RT-qPCR and Western blotting. RNAi and antibody blocking treatments were used to knockdown the expression of SLC7A5 or block its transporting function. Results The SLC7A5 expression was significantly upregulated in the FLS from RA patients compared with that in FLS from OA patients. Cytokine IL-1β played a crucial role in up-regulating SLC7A5 expression via NF-κB pathway in FLS. Intervening SLC7A5 expression with RNAi or blocking SLC7A5 function by monoclonal antibody could ameliorate the MMP3 and MMP13 protein expression. Furthermore, up regulation of SLC7A5 enhanced mTOR-P70SK6 signaling activation which could promote the protein translation of MMP3 and MMP13 in RA FLS. Conclusion SLC7A5 up-regulation could be induced by activated NF-κB pathway, further resulted in an enhanced mTOR-P70S6K activity and the protein expression of MMP3 and MMP13 in FLS from RA patients.

scholarly journals The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Li Zhu ◽  
Huaizhou Wang ◽  
Yu Wu ◽  
Zhengwen He ◽  
Yanghua Qin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Active Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Serum Levels ◽  
Serum Markers ◽  
Effector Cells ◽  
Joint Replacement Surgery ◽  
Replacement Surgery ◽  
Synovial Tissues

Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n=20) were significantly higher than those in OA patients (n=16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.

scholarly journals Loss of imprinting of IGF2 characterises high IGF2 mRNA-expressing type of fibroblast-like synoviocytes in rheumatoid arthritis

2009 ◽  
Vol 69 (6) ◽  
pp. 1239-1242 ◽  
Author(s):  
Alejandro Martin-Trujillo ◽  
Johanna G I van Rietschoten ◽  
Trieneke C G Timmer ◽  
Francisco Milena Rodríguez ◽  
Tom W J Huizinga ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Thymidine Incorporation ◽  
Biallelic Expression ◽  
Transcript Quantification ◽  
Loss Of Imprinting ◽  
Relative Contribution ◽  
Quantification Analysis ◽  
Allele Specific ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

ObjectiveIncreased expression of insulin-like growth factor 2 (IGF2) by fibroblast-like synoviocytes (FLS) was associated with low inflammatory synovium of patients with rheumatoid arthritis (RA). The aim of this study was to analyse whether the differential expression of IGF2, whose expression is normally restricted to one allele, is due to activation of the normally suppressed allele.MethodsIGF2 gene expression of RA FLS was quantified by quantitative real-time PCR. FLS heterozygous for a 3′-untranslated region IGF2 polymorphism were selected to measure the relative contribution of the allelic transcripts by allele-specific transcript quantification assay. Proliferation was determined by [3H]thymidine incorporation.ResultsIGF2 was shown to contribute to RA FLS proliferation. FLS could be classified in IGF2 high and IGF2 low-expressing cell lines. Allelic IGF2 transcript quantification analysis revealed that in part of the RA FLS the normally suppressed allele was activated, resulting in biallelic expression of the IGF2 gene. Biallelic expression was associated with increased levels of IGF2 mRNA production.ConclusionThe findings indicate that the imprinting status of IGF2 might underlie the increased expression of IGF2, which may contribute to autonomous growth of RA FLS of low inflammatory synovial tissues.

scholarly journals MiR-498 suppresses proliferation and inflammation in fibroblast-like synoviocytes in rheumatoid arthritis via targeting JAK1

2021 ◽  
Vol 18 (10) ◽  
pp. 2011-2017
Author(s):  
Lan Chai ◽  
Xian Zhen Zhang ◽  
Hai fang Ma ◽  
Fang Yuan
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Cycle ◽  
Polymerase Chain Reaction ◽  
Therapeutic Target ◽  
Cell Apoptosis ◽  
Inflammatory Responses ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

Purpose: To investigate the effect of microRNA 498 (miR-498) on proliferation and inflammation of rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLSs) in rheumatoid arthritis (RA). Methods: MiR-498 level was evaluated in both RA synovial tissues and RA-FLSs using real-time polymerase chain reaction (PCR). MicroRNA-498 overexpression or knockdown was performed in RAFLSs. Proliferation, apoptosis, cell cycle and inflammation induced by miR-498 mimics or inhibitor were used to explore the function of miR-498 in RA. Results: Expression level of miR-498 was downregulated in both RA synovial tissues and RA- FLSs. MicroRNA-498 mimics decreased proliferation and arrested cell cycle, whereas miR-498 inhibitor caused the opposite effects in RA-FLSs. In addition, miR-498 mimics suppressed inflammation and promoted cell apoptosis, while miR-498 inhibitor promoted inflammation and inhibited cell apoptosis in RA-FLSs. Furthermore, the effect of miR-498 on the proliferation, inflammation and apoptosis of RAFLSs was mediated by its ability to target and downregulate JAK1. Conclusion: These results indicate that miR-498 inhibits the proliferation and inflammatory responses of RA-FLSs by targeting JAK1, thus revealing a new therapeutic target for RA treatment.

scholarly journals Uridine Diphosphate (UDP) Promotes Rheumatoid Arthritis Through P2Y6 Activation

2020 ◽  
Author(s):  
Hongxing Wang ◽  
Hui Wu ◽  
Kehua Fang ◽  
Xiaotian Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Real Time ◽  
Proinflammatory Cytokines ◽  
Uridine Diphosphate ◽  
Synovial Fluids ◽  
Synovial Tissues ◽  
And Migration ◽  
G Protein Coupled ◽  
Fibroblast Like Synoviocytes

Abstract Background: Uridine diphosphate (UDP) is an extracellular nucleotide signaling molecule implicated in diverse biological processes via specific activation of pyrimidinergic receptor P2Y, G Protein-Coupled, 6 (P2Y6). There is very little knowledge about the function and mechanism of UDP in rheumatoid arthritis (RA).Methods: This study used a quasi-targeted liquid chromatography-mass spectrometry (LC-MS) approach to investigate the unique expression of metabolites in RA synovial fluids (SF) (n = 10) with samples from osteoarthritis (OA) as controls (n = 10). RA fibroblast-like synoviocytes (FLSs) were collected from synovial tissues (n = 5) and cultured with UDP or MRS2578, a P2Y6 antagonist, and FLSs from OA were used as controls (n = 5). Rats with collagen-induced arthritis (CIA) were injected with UDP, MRS2578 or both (n = 9 for each group). P2Y6 expression was examined using real-time PCR, Western blotting and immunohistochemistry. Cell proliferation, apoptosis and migration of RA FLSs were measured using CCK-8 assay, real-time cell analysis, flow cytometry, wound healing assay and Transwell assay, respectively. The UDP levels in the culture medium, synovial fluid (n = 36) and peripheral blood (n = 36) of RA and CIA rats were measured using a Transcreener UDP Assay. Levels of proinflammatory cytokines were measured using a flow assay. Interleukin-6 (IL-6) levels were measured using ELISA and flowResults：LC-MS analysis detected significantly increased UDP levels in RA SF compared with OA SF, and the level was positively correlated with anticyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) levels in RA. The increased UDP concentration was verified in the blood and synovial fluids of RA patients compared with samples from OA patients and healthy volunteers, respectively. UDP stimulated cell proliferation, migration and IL-6 secretion in RA FLSs and inhibited their apoptosis in culture, and MRS2578 inhibited these effects of UDP. UDP injection accelerated CIA and stimulated IL-6 production rather than other proinflammatory cytokines in the rat model, but simultaneous injection of MRS2578 suppressed these effects and alleviated CIA. P2Y6 expression was increased in RA and CIA synovial tissues.Conclusion: These results suggest that UDP is highly expressed in RA and stimulates RA pathogenesis by promoting P2Y6 activities to increase IL-6 production.

scholarly journals Lnc RNA ZFAS1 regulates the proliferation, apoptosis, inflammatory response and autophagy of fibroblast-like synoviocytes via miR-2682-5p/ADAMTS9 axis in rheumatoid arthritis

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Shanshan Yang ◽  
Wei Yin ◽  
Yan Ding ◽  
Fan Liu
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Inflammatory Response ◽  
Large Subunit ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Behaviors ◽  
Synovial Tissues ◽  
Related Proteins ◽  
Fibroblast Like Synoviocytes

Abstract Backgrounds: Rheumatoid arthritis (RA) is a frequent autoimmune disease. Emerging evidence indicated that ZNFX1 antisense RNA1 (ZFAS1) participates in the physiological and pathological processes in RA. However, knowledge of ZFAS1 in RA is limited, the potential work pathway of ZFAS1 needs to be further investigated. Methods: Levels of ZFAS1, microRNA (miR)-2682-5p, and ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to explore the ability of cell proliferation in fibroblast-like synoviocytes (FLS-RA). Cell apoptosis was measured via flow cytometry. Also, levels of ADAMTS9, apoptosis-related proteins, cleaved-caspase-3 (active large subunit), and autophagy-related proteins were identified adopting Western blot. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the productions of inflammatory cytokines. Beside, the interrelation between miR-2682-5p and ZFAS1 or ADAMTS9 was verified utilizing dual-luciferase reporter assay. Results: High levels of ZFAS1 and ADAMTS9, and a low level of miR-2682-5p were observed in RA synovial tissues and FLS-RA. Knockdown of ZFAS1 led to the curbs of cell proliferation, inflammation, autophagy, and boost apoptosis in FLS-RA, while these effects were abolished via regaining miR-2682-5p inhibition. Additionally, the influence of miR-2682-5p on cell phenotypes and inflammatory response were eliminated by ADAMTS9 up-regulation in FLS-RA. Mechanically, ZFAS1 exerted its role through miR-2682-5p/ADAMTS9 axis in RA. Conclusion: ZFAS1/miR-2682-5p/ADAMTS9 axis could modulate the cell behaviors, inflammatory response in FLS-RA, might provide a potential therapeutic target for RA treatment.

scholarly journals Uridine Diphosphate Promotes Rheumatoid Arthritis Through P2Y6 Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongxing Wang ◽  
Hui Wu ◽  
Kehua Fang ◽  
Xiaotian Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Real Time ◽  
Proinflammatory Cytokines ◽  
Uridine Diphosphate ◽  
Synovial Fluids ◽  
Synovial Tissues ◽  
And Migration ◽  
G Protein Coupled ◽  
Fibroblast Like Synoviocytes

BACKGROUND: Uridine diphosphate (UDP) is an extracellular nucleotide signaling molecule implicated in diverse biological processes via specific activation of pyrimidinergic receptor P2Y, G Protein-Coupled, 6 (P2Y6). There is very little knowledge about the function and mechanism of UDP in rheumatoid arthritis (RA).METHODS: This study used a quasi-targeted liquid chromatography-mass spectrometry (LC-MS) approach to investigate the unique expression of metabolites in RA synovial fluids (SF) (n = 10) with samples from osteoarthritis (OA) as controls (n = 10). RA fibroblast-like synoviocytes (FLSs) were collected from synovial tissues (n = 5) and cultured with UDP or MRS2578, a P2Y6 antagonist, and FLSs from OA were used as controls (n = 5). Rats with collagen-induced arthritis (CIA) were injected with UDP, MRS2578 or both (n = 9 for each group). P2Y6 expression was examined using real-time PCR, Western blotting and immunohistochemistry. Cell proliferation, apoptosis and migration of RA FLSs were measured using CCK-8 assay, real-time cell analysis, flow cytometry, wound healing assay and Transwell assay, respectively. The UDP levels in the culture medium, synovial fluid (n = 36) and peripheral blood (n = 36) of RA and CIA rats were measured using a Transcreener UDP Assay. Levels of proinflammatory cytokines were measured using a flow assay. Interleukin-6 (IL-6) levels were measured using ELISA and flow.RESULTS: LC-MS analysis detected significantly increased UDP levels in RA SF compared with OA SF, and the level was positively correlated with anticyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF)levels in RA. The increased UDP concentration was verified in the blood and synovial fluids of RA patients compared with samples from OA patients and healthy volunteers, respectively. UDP stimulated cell proliferation, migration and IL-6 secretion in RA FLSs and inhibited their apoptosis in culture, and MRS2578 inhibited these effects of UDP. UDP injection accelerated CIA and stimulated IL-6 production rather than other proinflammatory cytokines in the rat model, but simultaneous injection of MRS2578 suppressed these effects and alleviated CIA. P2Y6 expression was increased in RA and CIA synovial tissues.CONCLUSION: These results suggest that UDP is highly expressed in RA and stimulates RA pathogenesis by promoting P2Y6 activities to increase IL-6 production.

scholarly journals miR-431-5p regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis by targeting XIAP

2020 ◽  
Author(s):  
Yuejiao Wang ◽  
Kailin Zhang ◽  
Xiaowei Yuan ◽  
Neili Xu ◽  
Shuai Zhao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Real Time ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Proliferation And Apoptosis ◽  
Synovial Tissues ◽  
Proliferation Assays ◽  
Fibroblast Like Synoviocytes

Abstract Background miR-431-5p is dysregulated in various cancers and plays an important function in the development of cancer. However, its role in fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) remains to be understood.Methods Quantitative real-time polymerase chain reaction was used to detect the relative expression of miR-431-5p in synovial tissues and FLSs. Cell proliferation assays helped examine RA FLS proliferation. Flow cytometry was performed to determine apoptosis and cell cycle progression in RA FLSs. We used dual-luciferase assays to determine the correlation between miR-431-5p and its putative target, X-linked inhibitor of apoptosis (XIAP). Quantitative real-time PCR and western blotting were used to measure XIAP levels in synovial tissues and transfected RA FLSs.Results miR-431-5p was downregulated in synovial tissues and FLSs of patients with RA. Upregulation of miR-431-5p prohibited cell proliferation and the G0/G1-to-S phase transition, but promoted apoptosis in RA FLSs; while miR-431-5p inhibition showed the opposite results. miR-431-5p directly targeted XIAP in RA FLSs, and reversely correlated with XIAP levels in synovial tissues. Notably, XIAP silencing partially restored the effects of miR-431-5p inhibition in RA FLSs.Conclusion miR-431-5p regulates cell proliferation, apoptosis，and cell cycle of RA FLSs by targeting XIAP, suggesting its potential in the treatment of RA.

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