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Fibroblast Synoviocyte

Pallavi Bhattaram, Kyle Jones
Inflammation in the synovium is known to mediate joint destruction in several forms of arthritis. Fibroblast-like synoviocytes (FLS) are cells that reside in the synovial lining of joints and are known to be key contributors to inflammation associated with arthritis. FLS are a major source of inflammatory cytokines and catabolic enzymes that promote joint degeneration. We now know that there exists a direct correlation between the signaling pathways that are activated by the pro-inflammatory molecules produced by the FLS, and the severity of joint degeneration in arthritis...
March 13, 2019: Biochemical Pharmacology
Yunzhi Li, Ning He, Liqun Shen, Mingdong Liu
Aralia echinocaulis is used for the treatment of rheumatoid arthritis by Tujia Minority in China. A previous study demonstrated that A. echinocaulis had a significant anti-arthritic effect on adjuvant arthritis (AA) rats in vivo. However, it remains unclear whether A. echinocaulis can induce the apoptosis of fibroblast-like synoviocytes (FLS) from AA rats and the underlying mechanism is unknown. In this paper, CCK-8 assay, Hoechst staining and flow cytometry were used to evaluate the apoptotic effect of an A...
February 27, 2019: Journal of Pharmacological Sciences
Ray A Ohara, Gautam Edhayan, Stephanie M Rasmussen, Takeo Isozaki, Henriette A Remmer, Thomas M Lanigan, Phillip L Campbell, Andrew G Urquhart, Jeffrey N Lawton, Kevin C Chung, David A Fox, Jeffrey H Ruth
OBJECTIVE: We explored the intrinsic role of inhibitor of DNA binding 1 (ID1) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and investigated whether ID1 is citrullinated and autoantigenic in RA. METHODS: RA patient serum ID1 levels were measured before and after infliximab treatment. RA FLS were transfected with a CRISPR/Cas9 construct targeting ID1 to examine the effects of ID1 deletion. RA synovial fluids (SFs) and homogenized synovial tissues (STs) were immunoprecipitated for ID1 and measured for citrullinated residues using ELISA and Western blot...
March 12, 2019: Arthritis & Rheumatology
Xiao-Xi Hu, Yu-Jing Wu, Jing Zhang, Wei Wei
Rheumatoid arthritis (RA) is a chronic inflammatory synovitis-based systemic disease characterized by invasive joint inflammation and synovial hyperplasia, which can lead to arthrentasis and defunctionalization. Previous research has shown that T cells, B cells, dendritic cells (DCs), and fibroblast-like synoviocytes (FLSs) play vital roles in the regulation of RA. Both T follicular helper (Tfh) cells and helper T (Th) 17 cells play immunomodulatory roles in RA. Moreover, interleukin-23 (IL-23), and IL-17 are vital to the pathogenesis of RA...
March 8, 2019: International Immunopharmacology
Yiyue Chen, Wanchun Wang, You Chen, Qi Tang, Weihong Zhu, Ding Li, Lele Liao
Rheumatoid arthritis (RA) is a common chronic autoimmune disease and effective treatment for RA is still lacking. In this study, the regulatory role of miR-19a-3p in RA was investigated. Quantitative polymerase chain reaction analysis of human blood samples showed that the level of miR-19a-3p was significantly lower in the RA patients compared with that in healthy patients (P < 0.05). In RA fibroblast-like synoviocytes (RAFLS), miR-19a-3p and suppressor of cytokine signaling 3 (SOCS3) were also downregulated and upregulated, respectively, compared with those of normal FLS...
March 10, 2019: Journal of Cellular Biochemistry
Jianfeng Chen, Weibo Wu, Miaomiao Zhang, Caiming Chen
Previous study has indicated that taraxasterol (TAR), one of bioactive pentacyclic triterpenes mainly isolated from Chinese medicine herb Taraxacum officinale, displays considerable anti-inflammatory effects in various kinds of models. However, its effects on rheumatoid arthritis (RA) have still not been elucidated. In this study, we aim to investigate its anti-inflammatory effects and underlying mechanisms of TAR against RA using both interleukin (IL)-1β-stimulated human fibroblast-like synoviocytes rheumatoid arthritis (HFLS-RA) in vitro and collagen-induced arthritis (CIA) mice in vivo...
March 6, 2019: International Immunopharmacology
Teresina Laragione, Carolyn Harris, Percio S Gulko
The TRPV2 cation channel has been recently implicated in the regulation of arthritis severity, joint damage, and in the invasive behavior of the fibroblast-like synoviocyte (FLS). However, its mechanism of action was unknown. In this study we characterize the cell signaling events mediating the TRPV2 suppressive activity in FLS invasiveness. Studies with FLS cell lines derived from patients with RA revealed that TRPV2-specific stimulation significantly reduced FLS adhesion to different extracellular matrices that shared binding to αν, β1 and β3 integrins...
March 6, 2019: International Immunopharmacology
Hui-Peng Ma, Xue Deng, Deng-Yi Chen, Di Zhu, Jin-Ling Tong, Ting Zhao, Jin-Hui Ma, Yan-Qiu Liu
Targeting fibroblast-like synoviocyte (FLS) migration and invasion-mediated bone erosion is a promising clinical strategy for the treatment of rheumatoid arthritis (RA). Drug sensitivity testing is fundamental to this scheme. We designed a microfluidic chip-based, cell co-cultured platform to mimic RA FLS-mediated bone erosion and perform drug-sensitive assay. Human synovium SW982 cells were cultured in the central channel and migrated to flow through matrigel-coated side channels towards cell culture chamber where RANKL-stimulated osteoclastic RAW264...
September 2018: Royal Society Open Science
John P Caron, Jeffrey C Gandy, Jennifer L Brown, Lorraine M Sordillo
Omega-3 fatty acid (n-3 PUFA) supplementation may have beneficial effects in certain chronic diseases, potentially including osteoarthritis. Favorable effects are attributed, in part, to downstream pro-resolving oxylipid metabolites. We investigated the role of n-3 PUFA and docosahexaenoic acid (DHA)-derived oxylipids (docosanoids) on equine synoviocyte metabolism. We hypothesized that n-3 PUFA and selected docosanoids would modulate inflammatory mediator gene expression by recombinant equine (re)IL-1β-stimulated synovial fibroblasts...
March 2, 2019: Prostaglandins & Other Lipid Mediators
Martin Bonitz, Christiane Schaffer, Michael Amling, Ralf Poertner, Thorsten Schinke, Anke Jeschke
Although articular cartilage degeneration in osteoarthritis represents a major public health problem, there is still no molecular approach to prevent this pathology by blocking specific molecules. We have previously applied genome-wide expression analyses with porcine samples to identify specific markers of either growth plate or articular cartilage. Since the molecular differences were also found in cultured chondrocytes derived from both sites, we utilized primary porcine articular chondrocytes (PPACs) for the present study and analyzed, if and how they respond to synoviocyte-derived molecules...
February 27, 2019: Gene
Aurélie Najm, Frédéric Blanchard, Benoit Le Goff
Micro-RNAs are an area of research exponentially expanding over the past years. These small sequences of 20 to 22 nucleotides have a strong role as post-transcriptional regulators of gene expression. Inflammatory arthritis pathophysiology involves various key players from innate to adaptive immunity, as well as various signalling pathways of inflammation. In this review, we discuss how micro-RNAs are involved in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile inflammatory arthritis, from pre-clinical phases to established diseases...
February 27, 2019: Biochemical Pharmacology
Li-Min Liu, Jing-Tao Song, Feng Gao, Hui Zhang
OBJECTIVE: This study aims to analyze the effects of quinolones on synovium. METHODS: The present study explored the effects of levofloxacin on fibroblast-like synoviocyte (FLS) in vitro . After incubation with 10 ng/mL of interleukin-1β (IL-1β) for 24 hours, rabbit FLS were treated with serial concentrations of levofloxacin (0,14,28,56,112 and 224 μM) for 24 hours. The proliferation of FLS was assayed using the CCK-8 reagent. The mRNA expression levels of MMP-1, MMP-3, TIMP-1, COX-2, PEG2, IL-6, and caspase-3, -8 and -9 were evaluated using real-time PCR...
January 2019: Annals of Clinical and Laboratory Science
Qingyun Jia, Tengteng Wang, Xiaoyun Wang, Hao Xu, Yang Liu, Yongjun Wang, Qi Shi, Qianqian Liang
Astragalin, as a bioactive flavonoid with anti-inflammatory, antioxidant, and protective properties, provides a potential agent for rheumatoid arthritis (RA). In this study, its therapeutic efficacy and the underlying mechanisms were explored using DBA/1J mice with collagen-induced arthritis (CIA). It was demonstrated that astragalin could significantly attenuate inflammation of CIA mice. The effects were associated with decreased severity of arthritis (based on the arthritis index), joint swelling and reduced bone erosion and destruction...
2019: Frontiers in Pharmacology
Angel Bottini, Dennis J Wu, Rizi Ai, Michelle Le Roux, Beatrix Bartok, Michele Bombardieri, Karen M Doody, Vida Zhang, Cristiano Sacchetti, Martina Zoccheddu, Ana Lonic, Xiaochun Li, David L Boyle, Deepa Hammaker, Tzu-Ching Meng, Lin Liu, Maripat Corr, Stephanie M Stanford, Myles Lewis, Wei Wang, Gary S Firestein, Yeesim Khew-Goodall, Costantino Pitzalis, Nunzio Bottini
OBJECTIVE: We aimed to understand the role of the tyrosine phosphatase PTPN14-which in cancer cells modulates the Hippo pathway by retaining YAP in the cytosol-in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHODS: Gene/protein expression levels were measured by quantitative PCR and/or Western blotting. Gene knockdown in RA FLS was achieved using antisense oligonucleotides. The interaction between PTPN14 and YAP was assessed by immunoprecipitation...
February 26, 2019: Annals of the Rheumatic Diseases
M McLean, K McCall, I D M Smith, M Blyth, S M Kitson, L A N Crowe, W J Leach, B P Rooney, S J Spencer, M Mullen, J L Campton, I B McInnes, M Akbar, N L Millar
Objectives: Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations...
January 2019: Bone & Joint Research
Xin Lu, Jun Qian
Maternally expressed gene 3 (MEG3) in rheumatoid arthritis (RA) and its underlying mechanism were explored. Synovial tissues from 10 RA patients and 10 controls were collected to detect MEG3 expression in fibroblast-like synoviocytes (FLS). The relationship between MEG3 expression and TNF-α was analyzed. After MEG3 knockdown by lentivirus transfection, cell cycle, proliferation, apoptosis, invasion and secretion of inflammatory factors were detected. Furthermore, the effect of MEG3 on STAT3 and PI3K/AKT pathways was explored...
March 2019: Experimental and Therapeutic Medicine
Kunihiro Hayakawa, Mikiko Kawasaki, Takuya Hirai, Yuko Yoshida, Hiroshi Tsushima, Maki Fujishiro, Keigo Ikeda, Shinji Morimoto, Kenji Takamori, Iwao Sekigawa
MicroRNA (miRNA) is small RNA of 20 to 22 nucleotides in length and is stably present in plasma. Regulating the expression of miRNA taken into cells has been suggested as a general therapeutic approach. We identified the novel anti-inflammatory miRNA hsa-miR-766-3p and investigated its biological function in human rheumatoid arthritis (RA) fibroblast-like synoviocyte MH7A cells. To verify the function of the miRNA present in the plasma of RA patients, we performed a comprehensive analysis of the miRNA expression during abatacept treatment and identified eight miRNAs with significantly altered expression levels...
February 14, 2019: International Journal of Molecular Sciences
Li Zhang, Li Zhang, Zhengquan Huang, Runlin Xing, Xiaochen Li, Songjiang Yin, Jun Mao, Nongshan Zhang, Wei Mei, Liang Ding, Peimin Wang
Fibroblast-like synoviocytes (FLSs) are the main effector cells of knee osteoarthritis (KOA) synovial fibrosis. Our last report showed that NLRP1 and NLRP3 inflammasomes may mediate LPS/ATP-induced FLSs pyroptosis in KOA. In the present study, we found an elevated hypoxia-inducible factor-1 α (HIF-1 α ) level in the synovial tissue of KOA model rats, and inhibiting the increase of HIF-1 α could improve synovial fibrosis in rats. Subsequently, we established LPS/ATP-induced model in FLSs mimicking the inflammatory environment of KOA...
2019: Oxidative Medicine and Cellular Longevity
Chenqi Zhao, Nathalie Amiable, Melissa Laflamme, David Marsolais, John A Di Battista, Maria J Fernandes, Sylvain G Bourgoin
Sphingosine kinase 1 (SphK1) and 2 (SphK2) have been shown contribute to synovial inflammation in animal models of arthritis. However, low levels of intracellular sphingosine-1 phosphate (S1P) were reported in fibroblast-like synoviocytes (FLS) from patients in the end stage of rheumatoid arthritis (RA) compared to normal FLS. Moreover, the S1P receptor-mediated chemokine synthesis was altered in RAFLS in response to chemical hypoxia. Since the mechanisms responsible for low levels of intracellular S1P in RAFLS are not fully identified, we evaluated the contribution of SphKs to the S1P-induced synthesis of chemokines under conditions of chemical hypoxia...
February 9, 2019: Biochemical Pharmacology
T Cheng, M Wang, L Chen, Y Guo, Z Chen, J Wu
OBJECTIVE: Genetic studies have implicated both CD40 and tumour necrosis factor receptor-associated factor-1 (TRAF1) with rheumatoid arthritis (RA). CD40 signalling is known to be associated with TRAF1 expression, directly or indirectly; however, the detailed mechanisms of these interactions are not clear in RA, and in particular in fibroblast-like synoviocytes. This study aims to investigate this pathway and the role of nuclear factor-κB (NF-κB) in a mouse model of RA. METHOD: We utilized the collagen-induced arthritis (CIA) model in DBA/1 mice...
November 2018: Scandinavian Journal of Rheumatology
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