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Fibroblast Like Synoviocyte

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
Magdalena Massalska, Ewa Kuca-Warnawin, Iwona Janicka, Magdalena Plebanczyk, Dariusz Pawlak, Tomas Dallos, Anna Olwert, Anna Radzikowska, Pawel Maldyk, Ewa Kontny, Wlodzimierz Maslinski
OBJECTIVE: Rheumatoid arthritis (RA) is characterized by expansion of fibroblast-like synoviocytes (FLS) in inflamed joints and activation of lymphocytes. Tryptophan (trp) is an essential amino acid indispensable for the biosynthesis of proteins and critical for survival of lymphocytes. Indoleamine 2,3-dioxygenase (IDO) that initiates the degradation of trp and tryptophanyl-tRNA synthetase (TTS) essential for tryptophan synthesis, regulate trp bioavailability. Here, we tested the hypothesis that triggered by cytokines, enhanced IDO activity modulate regulatory function of otherwise non-tolerogenic FLS isolated from RA patients...
February 4, 2019: Immunopharmacology and Immunotoxicology
Liam J O'Neil, Mariana J Kaplan
Rheumatoid arthritis (RA), a common autoimmune disease, is characterized by a highly coordinated inflammatory response that involves innate and adaptive immunity. One of the hallmarks of RA is an immune response directed at citrullinated peptides that are specifically targeted by anticitrullinated protein antibodies (ACPAs). Among the various mechanisms by which neutrophils may promote immune dysregulation in RA, their ability to extrude neutrophil extracellular traps has recently been implicated in the development of ACPAs...
January 29, 2019: Trends in Molecular Medicine
M Vomero, V Manganelli, C Barbati, T Colasanti, A Capozzi, A Finucci, F R Spinelli, F Ceccarelli, C Perricone, S Truglia, S Morrone, R Maggio, R Misasi, M Bombardieri, M Di Franco, F Conti, M Sorice, G Valesini, C Alessandri
BACKGROUND: Autophagy has emerged as a key mechanism in the survival and function of T and B lymphocytes, and its activation was involved in apoptosis resistance in rheumatoid arthritis (RA). To investigate whether the relationship between autophagy and apoptosis may impact the response to the therapy, we analyzed ex vivo spontaneous autophagy and apoptosis in patients with RA subjected to treatment with anti-tumor necrosis factor (TNF) drugs and in vitro the effects of TNFα and anti-TNF drugs on cell fate...
January 29, 2019: Arthritis Research & Therapy
Kazuki Sugimoto, Takayuki Nakamura, Takuya Tokunaga, Yusuke Uehara, Tatsuya Okada, Takuya Taniwaki, Toru Fujimoto, Yuichi Oike, Eiichi Nakamura
Study Design: Experimental human study. Purpose: To determine whether angiopoietin-like protein 2 (ANGPTL2) is highly expressed in the hyperplastic facet joint (FJ) synovium and whether it activates interleukin-6 (IL-6) secretion in FJ synoviocytes. Overview of Literature: Mechanical stress-induced synovitis is partially, but significantly, responsible for degenerative and subsequently osteoarthritic changes in the FJ tissues in patients with lumbar spinal stenosis (LSS)...
January 29, 2019: Asian Spine Journal
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
Shirui Tan, Jian Xu, Aiyun Lai, Ruomei Cui, Ru Bai, Shu Li, Wei Liang, Guofang Zhang, Shaoquan Jiang, Shuang Liu, Mai Zheng, Wei Wang
The present study aimed to investigate the anti‑arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro, as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6, IL‑10, IL‑12 and IL‑17A. Furthermore, indices of the thymus and spleen were determined...
January 14, 2019: Molecular Medicine Reports
Katarzyna D Sluzalska, Gerhard Liebisch, Bernd Ishaque, Gerd Schmitz, Markus Rickert, Juergen Steinmeyer
Phospholipids (PLs) possess the unique ability to contribute to synovial joint lubrication. The aim of our study was to determine for the first time the effect of dexamethasone and some adrenergic and cholinergic agonists on the biosynthesis and release of PLs from human fibroblast-like synoviocytes (FLS). Osteoarthritic human knee FLS were treated with dexamethasone, terbutaline, epinephrine, carbachol, and pilocarpine, or the glucocorticoid receptor antagonist RU 486. Simultaneously PL biosynthesis was determined through the incorporation of stable isotope-labeled precursors into PLs...
January 15, 2019: International Journal of Molecular Sciences
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
Xiao-Yi Jia, Yan Chang, Fang Wei, Xing Dai, Yu-Jing Wu, Xiao-Jing Sun, Shu Xu, Hua-Xun Wu, Chun Wang, Xue-Zhi Yang, Wei Wei
Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a novel compound derived from paeoniflorin that has been demonstrated to have therapeutic effects in a rat model of rheumatoid arthritis (RA). However, the underlying mechanism has not been elucidated to date. We explored this mechanism in the present study by treating rats with adjuvant arthritis (AA) with CP-25. We found that the membrane EP4 protein level was downregulated; whereas, GRK2 was upregulated, in fibroblast-like synoviocyte (FLS)s of AA rats. Prostaglandin (PGE)2 stimulated FLS proliferation and enhanced the membrane EP4 receptor protein level; the latter was reversed by the administration of an EP4 receptor agonist, whereas the membrane GRK2 protein level gradually increased...
January 14, 2019: Acta Pharmacologica Sinica
Jie Gao, Ruina Kong, Xiaoli Zhou, Lianmei Ji, Ju Zhang, Dongbao Zhao
The authors would like to add an article note stating that "The authors Jie Gao and Ruina Kong have equally contributed to the article".
January 12, 2019: Apoptosis: An International Journal on Programmed Cell Death
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
Camilla R L Machado, Gustavo G Resende, Rafaela B V Macedo, Vanuza C do Nascimento, Angela S Branco, Adriana M Kakehasi, Marcus Vinicius Andrade
OBJECTIVES: The objective of the study was to compare the production of metalloproteinases (MMP)-1, -3 and interleukin (IL)-6 by fibroblast-like synoviocytes (FLS) derived from synovial fluid (FD-FLS), and FLS derived from synovial tissue (TD-FLS) of patients with primary osteoarthritis (OA). The more accessible FD-FLS could facilitate the study of the role of these cells in OA pathophysiology. METHODS: MMP-1, MMP-3, and IL-6 levels were measured in the supernatant culture at baseline and 22 hours after stimulation with TNF-α and IL-1 β...
December 19, 2018: Clinical and Experimental Rheumatology
Mark R Tanner, Michael W Pennington, Satendra S Chauhan, Teresina Laragione, Pércio S Gulko, Christine Beeton
BACKGROUND: Fibroblast-like synoviocytes (FLS) and CCR7- effector memory T (TEM ) cells are two of the major cell types implicated in the progression of rheumatoid arthritis (RA). In particular, FLS become highly invasive, whereas TEM cells proliferate and secrete proinflammatory cytokines, during RA. FLS and T cells may also interact and influence each other's phenotypes. Inhibition of the pathogenic phenotypes of both FLS and TEM cells can be accomplished by selectively blocking the predominant potassium channels that they upregulate during RA: KCa1...
January 7, 2019: Arthritis Research & Therapy
Laura E Hand, Suzanna H Dickson, Anthony J Freemont, David W Ray, Julie E Gibbs
BACKGROUND: The circadian clock plays a crucial role in regulating physiology and is important for maintaining immune homeostasis and responses to inflammatory stimuli. Inflammatory arthritis often shows diurnal variation in disease symptoms and disease markers, and it is now established that cellular clocks regulate joint inflammation. The clock gene Bmal1 is critical for maintenance of 24-h rhythms and plays a key role in regulating immune responses, as well as in aging-related processes...
January 6, 2019: Arthritis Research & Therapy
Xin Yan, Yake Liu, Xaoli Kong, Juan Ji, Hai Zhu, Zexu Zhang, Ting Fu, Junling Yang, Zhongyuan Zhang, Fan Liu, Zhifeng Gu
The function of microRNA-21-5p (miR-21) in fibroblast-like synoviocytes in RA was still unclear. In our study, we used tumor necrosis factor alpha (TNFα) (10 ng/ml) to mimic RA-FLSs and we found that normal FLS stimulated with TNFα caused the increasing expression of miR-21, a disintegrin and metalloproteinase with thrombospondin motifs 5 and matrix metalloproteinase 3, which were in accord with RA-FLSs changes. Our data showed that miR-21 overexpression significantly increased cell invasion and decreased apoptosis in FLSs...
January 1, 2019: Cytotechnology
Hae-Rim Kim, Bo-Mi Kim, Ji-Yeon Won, Kyung-Ann Lee, Hyun Myung Ko, Young Sun Kang, Sang-Heon Lee, Kyoung-Woon Kim
We investigated the immune-regulatory function of quercetin, in interleukin (IL)-17-produced osteoclastogenesis in rheumatoid arthritis (RA). RA fibroblasts-like synoviocytes (RA-FLS) were stimulated with IL-17, and the mRNA expression and secretion of receptor activator of nuclear factor kappa-B ligand (RANKL) were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. CD14+ monocytes (osteoclast precursors) were stimulated with IL-17, RANKL, with/without quercetin, and tartrate-resistant acid phosphatase activity was evaluated to assess osteoclast differentiation...
February 2019: Journal of Medicinal Food
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