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rheumatoid arthritis synovial fibroblast

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
Kunihiko Umekita, Shunichi Miyauchi, Hajime Nomura, Kazumi Umeki, Akihiko Okayama
OBJECTIVES: Damage-associated molecular patterns (DAMPs) are proposed to drive aberrant stimulation of Toll-like receptors (TLRs) in rheumatoid arthritis (RA) inflamed joints. In the current study we investigated the role of the neutrophil-derived lactoferrin (LTF), as an endogenous ligand for TLR4 in the inflammatory response of RA synovial fibroblasts (RASFs). METHODS: RASFs were stimulated with LTF, and the expressions of inflammatory cytokines in RASFs were measured...
February 11, 2019: Clinical and Experimental Rheumatology
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
Maria Fernanda Romo-García, Hilda Susana Nava-Ramírez, Martin Zapata-Zúñiga, Noe Macías-Segura, David Santiago-Algarra, Jose Dionisio Castillo-Ortiz, Yadira Bastián, Cesar Ramos-Remus, Jose Antonio Enciso-Moreno, Julio Enrique Castañeda-Delgado
Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by chronic and symmetrical inflammation of synovial tissue with subsequent joint destruction. SUMO1 is an important regulator of apoptosis through non-canonical mechanism in synovial fibroblasts, and POU2AF1 is a known B-cell transcriptional co-activator. The specific objective of this study was to measure the expression of SUMO1 and POU2AF1 on first-degree relatives of patients with RA and also in the preclinical and clinical stages of RA and describe their possible role in RA physiopathology...
January 25, 2019: International Journal of Immunogenetics
Bernhard Brandstetter, Karolina Dalwigk, Alexander Platzer, Birgit Niederreiter, Felix Kartnig, Anita Fischer, Gregory I Vladimer, Ruth A Byrne, Florian Sevelda, Johannes Holinka, Thomas Pap, Günter Steiner, Giulio Superti-Furga, Josef S Smolen, Hans P Kiener, Thomas Karonitsch
Fibroblast-like synoviocytes (FLS) are major contributors to joint inflammation in rheumatoid arthritis (RA). Forkhead box O 3 (FOXO3) perturbations in immune cells are increasingly linked to RA pathogenesis. Here, we show that FOXO3 is distinctly inactivated/phosphorylated in the FLS of rheumatoid synovitis. In vitro, stimulation of FLS with tumor necrosis factor-alpha α (TNFα) induced a rapid and sustained inactivation of FOXO3. mRNA profiling revealed that the inactivation of FOXO3 is important for the sustained pro-inflammatory interferon response to TNFα (CXCL9, CXCL10, CXCL11, and TNFSF18)...
January 24, 2019: Laboratory Investigation; a Journal of Technical Methods and Pathology
Maria Letizia Manca, Donatella Lattuada, Donatella Valenti, Ornella Marelli, Costantino Corradini, Xavier Fernàndez-Busquets, Marco Zaru, Anna Maria Maccioni, Anna Maria Fadda, Maria Manconi
In the present work curcumin loaded hyalurosomes were proposed as innovative systems for the treatment of rheumatoid arthritis. Vesicles were prepared using a one-step and environmentally friendly method. Aiming at finding the most suitable formulation in terms of size, surface charge and stability on storage, an extensive pre-formulation study was performed using different type and amount of phospholipids. Curcumin loaded vesicles prepared with 180 mg/ml of Phospholipon 90G (P90G) and immobilized with sodium hyaluronate (2 mg/ml) were selected because of their small size (189 nm), homogeneous dispersion (PI 0...
January 16, 2019: European Journal of Pharmaceutics and Biopharmaceutics
Emma R Dorris, Simon J Tazzyman, John Moylett, Nandhini Ramamoorthi, Jason Hackney, Michael Townsend, Munitta Muthana, Myles J Lewis, Costantino Pitzalis, Anthony G Wilson
Genetic variants in C5orf30 have been associated with development of the autoimmune conditions primary biliary cirrhosis and rheumatoid arthritis. In rheumatoid arthritis, C5orf30 expression is cell-specific, with highest expression found in macrophages and synovial fibroblasts. C5orf30 is highly expressed in inflamed joints and is a negative regulator of tissue damage in a mouse model of inflammatory arthritis. Transcriptomic analysis from ultrasound-guided synovial biopsy of inflamed joints in a well characterized clinical cohort of newly diagnosed, disease-modifying antirheumatic drugs-naive rheumatoid arthritis patients was used to determine the clinical association of C5orf30 expression with disease activity...
January 18, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Meilang Xue, Suat Dervish, Kelly J McKelvey, Lyn March, Fang Wang, Chris B Little, Christopher J Jackson
Objectives: To investigate whether activated protein C (APC), a physiological anticoagulant can inhibit the inflammatory/invasive properties of immune cells and rheumatoid arthritis synovial fibroblasts (RASFs) in vitro and prevent inflammatory arthritis in murine antigen-induced arthritis (AIA) and CIA models. Methods: RASFs isolated from synovial tissues of patients with RA, human peripheral blood mononuclear cells (PBMCs) and mouse thymus cells were treated with APC or TNF-α/IL-17 and the following assays were performed: RASF proliferation and invasion by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell invasion assays, respectively; cytokines and signalling molecules using ELISA or western blot; Th1 and Th17 phenotypes in human PBMCs or mouse thymus cells by flow cytometry...
January 10, 2019: Rheumatology
Chien-Chung Huang, Chen-Hsiang Chiou, Shan-Chi Liu, Sung-Lin Hu, Chen-Ming Su, Chun-Hao Tsai, Chih-Hsin Tang
The hormone melatonin has many properties, including antioxidant, anti-inflammatory and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose-dependently inhibits tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β expression through the PI3K/AKT, ERK and NF-κB signaling pathways...
January 16, 2019: Journal of Pineal Research
Ya-Ru Liu, Lei Yang, Qing-Qing Xu, Xin-Yi Lu, Tao-Tao Ma, Cheng Huang, Jun Li
Rheumatoid arthritis (RA) is one of the chronic systemic autoimmune diseases that cardinally affect the joints. Many people all over the world suffer from the disease. Fibroblast-like synoviocytes (FLSs) play a significant role in the occurrence and development of RA. The long noncoding RNA maternally expressed gene 3 (MEG3) is an imprinted gene, which participates in various cancers as a tumor suppressor. Previous studies have shown that nucleotide oligomerization domain (NOD)-like receptors 5 (NLRC5) plays a key role in inflammatory and autoimmune diseases...
January 15, 2019: Journal of Cellular Physiology
Binbin Ci, Wenjun Wang, Yongan Ni
To study the mechanism and inhibitory effect of Saposhnikovia divaricata polysaccharide (SDP) on fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis rat model. Rheumatoid arthritis rat model was established by the classical composite factors including wind, cold, damp plus biological agents. The synovial tissues were digested with trypsin to isolate FLS cells. The different dosage of SDP was applied in culture. The cell viability was evaluated by MTT assay and the apoptosis was determined by analytic flow cytometry...
November 2018: Pakistan Journal of Pharmaceutical Sciences
Mohammed H Abuwarwar, Konstantin Knoblich, Anne L Fletcher
No abstract text is available yet for this article.
November 2018: Annals of Translational Medicine
H Q Niu, X C Zhao, W P Zhao, X F Li
No abstract text is available yet for this article.
January 1, 2019: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
Elena Neumann, Rebecca Hasseli, Uwe Lange, Ulf Müller-Ladner
Chronic inflammation, synovial hyperplasia, and local hypoxia lead to synovial cell activation causing severe joint damage in chronic-inflammatory rheumatoid arthritis (RA). The pro-inflammatory and joint-destructive property of the increased release of extracellular nucleic acids has been demonstrated for extracellular mitochondrial DNA and oxidized DNA using an arthritis model. Microparticles derived from different cells are able to transport nucleic acids to distant cells and promote cellular activation in RA...
January 2, 2019: Current Pharmaceutical Biotechnology
Jing Wu, Yuan Qu, Yu-Ping Zhang, Jia-Xin Deng, Qing-Hong Yu
BACKGROUND: Rheumatoid arthritis (RA) is a chronic and refractory autoimmune joint disease. Fibroblast-like synoviocytes (FLS) produce inflammatory cytokines and are involved in the migration and invasion of panuus tissue, which leads to the destruction of joints in RA. Receptor for hyaluronan mediated motility (RHAMM), is known to be one of the important receptors for hyaluronic acid. It has the ability to regulate migration of fibrocytes and infiltration of inflammatory cells. Here,we explored the mechanisms of RHAMM in RAFs...
December 26, 2018: BMC Musculoskeletal Disorders
Qiaoding Dai, Di Zhou, Liping Xu, Xinwei Song
Purpose: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and symmetric polyarthritis. Mammalian target of rapamycin (mTOR) was reported to be a new target for RA therapy and its inhibitor rapamycin can significantly reduce the invasive force of fibroblast-like synoviocytes. Here, we determined the effect of curcumin to alleviate inflammation and synovial hyperplasia for the therapy of RA. Materials and methods: Collagen-induced arthritis (CIA) was developed in Wistar rats and used as a model resembling RA in humans...
2018: Drug Design, Development and Therapy
Yao Yao, Haixia Yu, Yaru Liu, Qingqing Xu, Xiaofeng Li, Xiaoming Meng, Cheng Huang, Jun Li
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease and its pathogenesis remains unclear. Fibroblast-like synoviocytes (FLSs) play an important role in the pathogenesis of RA. Proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) is an adaptor protein, which is associated with auto-inflammatory disease. In this study, we selected adjuvant-induced arthritis (AIA) as animal model to study the role of PSTPIP2 in FLSs. We found that the expression of PSTPIP2 was significantly down-regulated in synovial tissues and FLSs of AIA rat compared with normal group...
2018: Frontiers in Pharmacology
Minxi Lao, Zhongping Zhan, Nan Li, Siqi Xu, Maohua Shi, Yaoyao Zou, Mingcheng Huang, Shan Zeng, Liuqin Liang, Hanshi Xu
Rheumatoid arthritis (RA) is featured by erosive cartilage and bone destruction. The enhancing aggressive property of fibroblast-like synoviocytes (FLSs) plays a critical role in this process. Small ubiquitin-like modifier (SUMO) proteins, including SUMO-1, SUMO-2, SUMO-3 and SUMO-4, participate in regulating many cellular events such as survival, migration and signal transduction in some cell lines. However, their roles in the pathogenesis of RA are not well established. Therefore, we evaluated the role of SUMO proteins in RA FLSs migration and invasion...
December 15, 2018: Experimental Cell Research
Nan Li, Zhaohui Gong, Xiaojuan Li, Qingyu Ma, Mansi Wu, Dongdong Liu, Lijuan Deng, Dongmei Pan, Qingping Liu, Zhenquan Wei, Qiang Wang, Longyin Han, Changsong Lin, Jiaxu Chen
The aggressive phenotype displayed by fibroblast-like synoviocytes (FLSs) contributes to cartilage and bone destruction in rheumatoid arthritis (RA). Betulinic acid has been demonstrated to have a positive therapeutic effect on tumor, inflammation and immune disorder, however, the effects of betulinic acid on RA FLSs have not been verified. Therefore, in the present study, we observed the effect of betulinic acid on the migration and invasion of RA FLSs and explored its underlying signal mechanisms. Our results showed that betulinic acid treatment suppressed the migration, invasion and reorganization of the actin cytoskeleton of RA FLSs...
December 13, 2018: International Immunopharmacology
Fang-Yuan Yu, Cong-Qin Xie, Chang-Liang Jiang, Ji-Tong Sun, Hui-Cheng Feng, Chao Li, Xun-Wu Huang
Growing data have indicated that the miR-17-92 cluster is implicated in inflammatory response and rheumatoid arthritis (RA). This study was aimed to investigate the effects of miR-92a on the proliferation and migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Our results showed that miR-92a was significantly down-regulated in RA synovial tissue and RA-FLSs, whereas the protein level of AKT2 is increased. Restoration of miR-92a suppressed the proliferation and migration of RA-FLSs. Down-regulation of miR-92a promotes proliferation and migration of normal human FLSs...
December 2018: Journal of Biosciences
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