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Fibroblast Like Synoviocyte

Xin Wang, Xueping Wang, Jin Sun, Shiou Fu
Rheumatoid arthritis (RA) is considered to be a systemic autoimmune disease that induces systemic complications and progressive disability. It affects a large number of people. RA fibroblast‑like synoviocytes (RA‑FLS) promote the progression of RA through the secretion of proinflammatory cytokines and increasing invasiveness into the extracellular matrix. Therefore, targeting RA‑FLS represents a potential approach for the treatment of RA. Ribonucleotide reductase M2 (RRM2), a critical protein for DNA synthesis and repair, may promote the proliferation of cells and inhibit cellular apoptosis...
August 8, 2018: International Journal of Molecular Medicine
Maohua Shi, Jingnan Wang, Youjun Xiao, Cuicui Wang, Qian Qiu, Minxi Lao, Yangtao Yu, Zhifeng Li, Hongwei Zhang, Yujin Ye, Liuqin Liang, Xiuyan Yang, Guoqiang Chen, Hanshi Xu
Objective: To investigate the role of glycogen metabolism in regulating rheumatoid fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and its underlying mechanism. Methods: FLSs were separated from synovial tissues (STs) obtained from rheumatoid arthritis (RA) patients. Glycogen content was determined by periodic acid Schiff staining. Protein expression was analyzed by Western blot or immunohistochemistry. Gene expression of cytokines and matrix metalloproteinases (MMPs) was evaluated by quantitative real-time PCR...
2018: Frontiers in Immunology
Aurore De Cauwer, Alexandre Mariotte, Jean Sibilia, Seiamak Bahram, Philippe Georgel
Loss-of-function or knockout mouse models have established a fundamental role for the RNAse III enzyme DICER1 in development and tissue morphogenesis and/or homeostasis. These functions are currently assumed to result mainly from the DICER1-dependent biogenesis of microRNAs which exhibit important gene expression regulatory properties. However, non-canonical DICER1 functions have recently emerged. These include interaction with the DNA damage response (DDR) pathway and the processing of cytotoxic non-coding RNAs, suggesting that DICER1 might also participate in the regulation of major cellular processes through miRNA-independent mechanisms...
2018: Frontiers in Immunology
Dorota Trzybulska, Anna Olewicz-Gawlik, Jan Sikora, Magdalena Frydrychowicz, Agata Kolecka-Bednarczyk, Mariusz Kaczmarek, Pawel Hrycaj
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease leading to destructive changes in peripheral joints and their irreversible deformity. The influx of chemoattractant-mediated inflammatory cells to the joints is one of the main features of RA. OBJECTIVES: The aim of this study was to investigate the effect of a knockdown of caveolin-1 (CAV1), a known regulator of multiple cell signaling pathways, on chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) expression in synovial fluid-derived fibroblast-like synoviocytes (sfd-FLSs) obtained from patients with RA...
August 6, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Xiaokang Li, Yahui Huang, Junfei Cheng, Lingling Zhang, Fei Mao, Jin Zhu, Chunquan Sheng, Jian Li
Due to the complex biological pathways involved in rheumatoid arthritis, discovery of multi-targeting small molecules provides an effective strategy to achieve better efficacy and lower toxicity. Herein the first Syk/PDGFR-α/c-Kit inhibitors were designed and evaluated. Dihydrofuropyrimidine derivative 13 showed potent inhibitory activity against the three targets. Importantly, compound 13 exhibited good cellular efficacy against fibroblast-like synoviocytes (IC50  = 3.21 μM) and mouse bone marrow-derived mast cells (IC50  = 2...
June 22, 2018: Bioorganic & Medicinal Chemistry
Hiroyuki Nakamura, Sanae Shimamura, Shinsuke Yasuda, Michihito Kono, Michihiro Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Tomohiro Shimizu, Norimasa Iwasaki, Tatsuya Atsumi
OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel therapeutic strategy for treatment-resistant RA is still awaited. In this study, we analysed the expression and function of Ras guanine nucleotide-releasing proteins (RASGRPs), guanine exchange factors for small GTPase Ras, in FLS as a potential therapeutic target for RA...
August 3, 2018: Annals of the Rheumatic Diseases
Sho Ishii, Takeo Isozaki, Hidekazu Furuya, Hiroko Takeuchi, Yumi Tsubokura, Katsunori Inagaki, Tsuyoshi Kasama
BACKGROUND: To examine the expression of ADAM-17 in rheumatoid arthritis (RA) biological fluids and the role it plays in monocyte adhesion to RA fibroblast-like synoviocytes (FLSs). METHODS: ADAM-17 expression was measured by enzyme-linked immunosorbent assays (ELISAs) in serum from normal (NL) subjects, osteoarthritis (OA) patients, and RA patients. We also analyzed the correlation between ADAM-17 and disease activity score 28 (DAS28) in RA. To determine expression of ADAM-17 in RA synovial tissues (STs) and RA FLS, we performed immunofluorescence analyses...
August 2, 2018: Arthritis Research & Therapy
Sang-Heon Park, Jinseol Rhee, Seul-Ki Kim, Jung-Ah Kang, Ji-Sun Kwak, Young-Ok Son, Wan-Su Choi, Sung-Gyoo Park, Jang-Soo Chun
BACKGROUND: We recently demonstrated that BATF, a member of the activator protein-1 (AP-1) family, regulates osteoarthritic cartilage destruction. Here, we explored the roles and regulatory mechanisms of BATF in collagen-induced arthritis (CIA) in mice. METHODS: CIA and K/BxN serum transfer were used to generate inflammatory arthritis models in wild-type (WT) and Batf-/- mice. RA manifestations were determined by examining CIA incidence, clinical score, synovitis, synovial hyperplasia, angiogenesis in inflamed synovium, pannus formation, bone erosion, and cartilage destruction...
August 2, 2018: Arthritis Research & Therapy
Marta F Bustamante, Patricia G Oliveira, Ricard Garcia-Carbonell, Adam P Croft, Jeff M Smith, Ramon L Serrano, Elsa Sanchez-Lopez, Xiao Liu, Tatiana Kisseleva, Nissim Hay, Christopher D Buckley, Gary S Firestein, Anne N Murphy, Shigeki Miyamoto, Monica Guma
OBJECTIVES: Recent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage. METHODS: HK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry...
July 30, 2018: Annals of the Rheumatic Diseases
Zhaohui Yu, Hua Xu, Hailin Wang, Youhua Wang
Forkhead box c1 (Foxc1) is a vital member of the Fox family of transcription factors which play important roles in numerous biological processes including metabolism, differentiation, proliferation, apoptosis, migration, invasion and longevity. However, up to date, the role of Foxc1 in the development of Rheumatoid Arthritis (RA) has not been fully elucidated. In the present study, the markedly higher expression of Foxc1 was observed in fibroblast-like synoviocytes (FLSs) of RA compared to control. Besides, we found that Foxc1 had a co-localization with THY1 (a marker for fibroblast-like synoviocytes)...
August 2018: Tissue & Cell
Teresina Laragione, Max Brenner, Amit Lahiri, Erjing Gao, Carolyn Harris, Percio S Gulko
OBJECTIVES: While new treatments for rheumatoid arthritis (RA) have markedly improved disease control by targeting immune/inflammatory pathways, current treatments rarely induce remission, underscoring the need for therapies that target other aspects of the disease. Little is known about the regulation of disease severity and joint damage, which are major predictors of disease outcome, and might be better or complementary targets for therapy. In this study, we aimed to discover and characterise a new arthritis severity gene...
July 26, 2018: Annals of the Rheumatic Diseases
Elisa Corsiero, Lucas Jagemann, Mauro Perretti, Costantino Pitzalis, Michele Bombardieri
Rheumatoid arthritis (RA) is characterized by formation of synovial ectopic lymphoid structures (ELS) supporting B cell autoreactivity toward locally generated citrullinated (cit) antigens, including those contained in neutrophil extracellular traps (NETs). However, only a minority of RA-rmAbs from B cells isolated from ELS+ RA tissues react against NETs. Thus, alternative cellular sources of other potential autoantigens targeted by locally differentiated B cells remain undefined. RA fibroblast-like synoviocytes (FLS) have been implicated in the release of RA-associated autoantigens...
July 25, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Chiara Angiolilli, Pawel A Kabala, Aleksander M Grabiec, Marzia Rossato, Wi S Lai, Gianluca Fossati, Paolo Mascagni, Christian Steinkühler, Perry J Blackshear, Kris A Reedquist, Dominique L Baeten, Timothy R D J Radstake
BACKGROUND: Histone deacetylase inhibitors (HDACi) suppress cytokine production in immune and stromal cells of patients with rheumatoid arthritis (RA). Here, we investigated the effects of the HDACi givinostat (ITF2357) on the transcriptional and post-transcriptional regulation of inflammatory markers in RA fibroblast-like synoviocytes (FLS). METHODS: The effects of ITF2357 on the expression and messenger RNA (mRNA) stability of IL-1β-inducible genes in FLS were analyzed using array-based qPCR and Luminex...
July 20, 2018: Arthritis Research & Therapy
Cheng-Gui Miao, You-Yi Xiong, Mei-Song Qing, Hao Chen, Jun Chang
OBJECTIVE: The therapeutic effect and mechanism of total flavonoids in Isodon amethystoides (Ben-th) Cy Wu et Hsuan (TFIA) on adjuvant arthritis (AA) were investigated. METHODS: AA model rats were set and complete Freund's adjuvant injection,randomly divided into 4 groups: AA group,AA+TFIA 50 mg/kg group,AA+TFIA 100 mg/kg group,AA+TFIA 150 mg/kg group,and each group has 10 rats. Blank control group was set without modeling ( n =10). Four days post-modeling rats in each TFIA groups were treated once a day with TFIA at 50 mg/kg,100 mg/kg and 150 mg/kg for 24 d,and rats in blank control and AA groups were given saline as control...
May 2018: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Lang Yi, Yan-Jun Lyu, Chong Peng, Rui-Li Zhu, Sha-Sha Bai, Liang Liu, Pei-Xun Wang, Hua Zhou, Yan Dong
No abstract text is available yet for this article.
July 12, 2018: International Immunopharmacology
Jiajie Tu, Wenming Hong, Pengying Zhang, Xinming Wang, Heinrich Körner, Wei Wei
Fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS) are the two main cellular components of the synovium. It has been widely reported that FLS and MLS play essential roles in the joint pathology of rheumatoid arthritis (RA). Although various studies have analyzed both human and animal tissues and have shown that both cell types are involved in different stages of RA, ontology, and specific functions of both cell populations and their interactions are not well understood. In this review, we will summarize recent research on FLS and MLS in RA and focus on the development and function of two predominant synovial cell types...
2018: Frontiers in Immunology
Seungjin Choi, Kijun Lee, Hyerin Jung, Narae Park, Jaewoo Kang, Ki-Hoan Nam, Eun-Kyeong Kim, Ji Hyeon Ju, Kwi Young Kang
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes mild to severe joint inflammation. During RA pathogenesis, fibroblast-like synoviocytes (FLS) acquire a tumor-like phenotype and mediate cartilage destruction both directly and indirectly by producing proinflammatory cytokines and matrix metalloproteinases (MMPs). Kruppel-like factor (KLF) 4, a member of the KLF family, plays significant roles in cell survival, proliferation, and differentiation. A recent study reported increased expression of KLF4 in synovial tissue from RA patients...
2018: Frontiers in Immunology
Mascha Koenen, Stephan Culemann, Sabine Vettorazzi, Giorgio Caratti, Lucien Frappart, Wolfgang Baum, Gerhard Krönke, Ulrike Baschant, Jan P Tuckermann
BACKGROUND: Glucocorticoid (GC) therapy is frequently used to treat rheumatoid arthritis due to potent anti-inflammatory actions of GCs. Direct actions of GCs on immune cells were suggested to suppress inflammation. OBJECTIVES: Define the role of the glucocorticoid receptor (GR) in stromal cells for suppression of inflammatory arthritis. METHODS: Bone marrow chimeric mice lacking the GR in the hematopoietic or stromal compartment, respectively, and mice with impaired GR dimerisation (GRdim ) were analysed for their response to dexamethasone (DEX, 1 mg/kg) treatment in serum transfer-induced arthritis (STIA)...
July 11, 2018: Annals of the Rheumatic Diseases
Valeria Manganelli, Serena Recalchi, Antonella Capozzi, Gloria Riitano, Vincenzo Mattei, Agostina Longo, Manuela Di Franco, Cristiano Alessandri, Michele Bombardieri, Guido Valesini, Roberta Misasi, Tina Garofalo, Maurizio Sorice
Objectives: Autophagy is a homeostatic and physiological process that promotes the turnover of proteins and organelles damaged in conditions of cellular stress. We previously demonstrated that autophagy represents a key processing event creating a substrate for autoreactivity, which is involved in post-translational changes and generation of citrullinated peptides, recognized by the immune system in RA. In this study, we analysed whether autophagy is involved in other post-translational changes that can generate autoantigens, focusing on carbamylation processes...
July 3, 2018: Rheumatology
Yusuke Yoshida, Satoshi Yamasaki, Katsuhiro Oi, Tatsuomi Kuranobu, Takaki Nojima, Shigeru Miyaki, Hiroaki Ida, Eiji Sugiyama
Aberrant endochondral bone formation in the physis is a unique bone lesion in neonatal-onset multisystem inflammatory disease (NOMID), also called chronic infantile neurologic cutaneous articular (CINCA), the most severe of the cryopyrin-associated periodic syndrome (CAPS) diseases, which are interleukin-1β (IL-1β)-related monogenic autoinflammatory diseases. The wingless (Wnt) pathway plays an important role in osteoblast differentiation. In this study, we explored the potential role of IL-1β on the expression of WNT genes and the Wnt antagonist Dickkopf-1 (DKK1)...
June 28, 2018: Inflammation
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