We previously reported that sialyl Lewisy, synthesized by fucosyltransferases, is involved in angiogenesis. Fucosyltransferase 1 (fut1) is an α(1,2)-fucosyltransferase responsible for synthesis of the H blood group and Lewisy antigens. However, the angiogenic involvement of fut 1 in the pathogenesis of rheumatoid arthritis synovial tissue (RA ST) has not been clearly defined. Assay of α(1,2)-linked fucosylated proteins in RA was performed by enzyme-linked lectin assay. Fut1 expression was determined in RA ST samples by immunohistological staining. We performed angiogenic Matrigel assays using a co-culture system of human dermal microvascular endothelial cells (HMVECs) and fut1 small interfering RNA (siRNA) transfected RA synovial fibroblasts. To determine if fut1 played a role in leukocyte retention and cell proliferation in the RA synovium, myeloid THP-1 cell adhesion assays and fut1 siRNA transfected RA synovial fibroblast proliferation assays were performed. Total α(1,2)-linked fucosylated
We previously reported that sialyl Lewisy, synthesized by fucosyltransferases, is involved in angiogenesis. Fucosyltransferase 1 (fut1) is an α(1,2)-fucosyltransferase responsible for synthesis of the H blood group and Lewisy antigens. However, the angiogenic involvement of fut 1 in the pathogenesis of rheumatoid arthritis synovial tissue (RA ST) has not been clearly defined. Assay of α(1,2)-linked fucosylated proteins in RA was performed by enzyme-linked lectin assay. Fut1 expression was determined in RA ST samples by immunohistological staining. We performed angiogenic Matrigel assays using a co-culture system of human dermal microvascular endothelial cells (HMVECs) and fut1 small interfering RNA (siRNA) transfected RA synovial fibroblasts. To determine if fut1 played a role in leukocyte retention and cell proliferation in the RA synovium, myeloid THP-1 cell adhesion assays and fut1 siRNA transfected RA synovial fibroblast proliferation assays were performed. Total α(1,2)-linked fucosylated
TY - JOUR. T1 - Annexin-1 mediates TNF-α-stimulated matrix metalloproteinase secretion from rheumatoid arthritis synovial fibroblasts. AU - Tagoe, Clement E.. AU - Marjanovic, Nada. AU - Park, Jean Y.. AU - Chan, Edwin S.. AU - Abeles, Aryeh M.. AU - Attur, Mukundan. AU - Abramson, Steven B.. AU - Pillinger, Michael H.. PY - 2008/8/15. Y1 - 2008/8/15. N2 - Annexins are intracellular molecules implicated in the down-regulation of inflammation. Recently, annexin-1 has also been identified as a secreted molecule, suggesting it may have more complex effects on inflammation than previously appreciated. We studied the role of annexin-1 in mediating MMP-1 secretion from rheumatoid arthritis (RA) synovial fibroblasts (SF) stimulated with TNF-α. TNF-α induced a biphasic secretion of annexin-1 from RA SF. Early (≤60 min), cycloheximide-independent secretion from preformed intracellular pools was followed by late (24 h) cycloheximide-inhibitable secretion requiring new protein synthesis. Exogenous ...
Results Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation.. ...
High-density lipoproteins downregulate CCL2 production in human fibroblast-like synoviocytes stimulated by urate crystals. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus, which has shown anti-oxidant, anti-cancer and anti-inflammatory activities. In this study, we investigated the effects of hyperoside on human rheumatoid fibroblast-like synoviocytes (FLSs) in vitro and on mouse collagen-induced arthritis (CIA) in vivo. FLSs were isolated from primary synovial tissues obtained from rheumatoid arthritis (RA) patients and exposed to LPS (1 μg/mL). Cell viability and proliferation were measured with MTT and BrdU assay. Cell migration was assessed using wound-healing assay and Transwell assay. DNA binding of NF-κB was measured using a TransAM-NFkappaB kit. The localization of p65 subunit was detected with immunocytochemistry. CIA was induced in mice by primary immunization with Bovine Type II collagen (CII) emulsified in CFA, followed by a booster injection 3 weeks later. The arthritic mice were treated with hyperoside (25, 50 mg·kg−1·d−1, ip) for 3 weeks, and the joint
Our data suggest that modulation of class 3 semaphorin signaling could be a novel therapeutic strategy for modulating the invasive behaviour of FLS in RA.
OBJECTIVE--The effects were studied of interleukin 4 (IL-4) on T cell-synovial cell adhesion and on the expression of adhesion molecules on the surface of synovial fibroblast-like cells. METHODS--The adhesion of T cells toward the synovial cells were measured by 51chromium-labelled adhesion assay. The expression of adhesion molecules on synovial cells were analysed by flowcytometry. RESULTS--Stimulation of synovial cells with IL-4 increased T cell-synovial cells adhesion in a time- and dose-dependent manner. IL-4 considerably enhanced the expression of VCAM-1 on the surface of synovial cells, but not the expression of ICAM-1 and ELAM-1. The combination of IL-1 beta and IL-4 had no effect on the expression of ICAM-1 or VCAM-1 on the surface of synovial cells. The increased adhesion of T cells to IL-4 stimulated synovial cells was inhibited significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody. Furthermore, anti-VLA-4 alpha or the combination of anti-VLA-4 alpha and anti-VCAM-1 ...
PubMed journal article: Reduction of synovial sublining layer inflammation and proinflammatory cytokine expression in psoriatic arthritis treated with methotrexate. Download Prime PubMed App to iPhone, iPad, or Android
Transforming growth factor (TGF)-beta has been shown to promote tissue repair and have immunosuppressive actions, and has been proposed to have a role in rheumatoid arthritis (RA). Using immunohistochemical techniques with rabbit F(ab)2 antibodies raised against recombinant human TGF-beta 1, we have detected TGF-beta 1 in the synovial tissue and cartilage/pannus junction (CPJ) from 18/18 patients with RA. TGF-beta 1 was found predominantly in the thickened synovial lining layer in RA, but also detected in a perivascular pattern in the synovial interstitium as well as in occasional cells in the lymphoid aggregates. At the CPJ it was found both in cells at the distinct junction as well as in the transitional region of the diffuse fibroblastic zone. The cells staining for TGF-beta 1 were identified by double immunofluorescence staining as being from the monocyte/macrophage series as well as the type B synovial lining cells. TGF-beta 1 was also detected in the synovial membrane sections from 4/4 patients
Title:α-Mangostin, A Natural Xanthone, Induces Apoptosis and ROS Accumulation in Human Rheumatoid Fibroblast-Like Synoviocyte MH7A Cells. VOLUME: 17 ISSUE: 5. Author(s):J. Zhang*, Q. Chen, S. Wang, T. Li, Z. Xiao, W. Lan, G. Huang and X. Cai*. Affiliation:The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, Department of Rheumatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, Department of Rheumatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, Department of Orthopaedics, Guangdong Provincial Hospital of Traditional Chinese ...
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Authors: Tang CH, Hsu CJ, Yang WH, Fong YC. Patients with rheumatoid arthritis (RA) are at increased risk of developing infections and appear to be particularly susceptible to septic arthritis. Lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria is an amphiphilic, negatively charged glycolipid. However, the effects of LTA on human synovial fibroblasts are largely unknown. We investigated the signaling pathway involved in IL-6 production stimulated by LTA in rheumatoid arthritis synovial fibroblasts (RASF). LTA caused concentration- and time-dependent increases in IL-6 production. LTA-mediated IL-6 production was attenuated by Toll-like receptor 2 (TLR2) monoclonal antibody or siRNA. Pretreatment with PKCdelta inhibitor (rottlerin), c-Src inhibitor (PP2), AP-1 inhibitor (tanshinone IIA) and NF-kappaB inhibitor (PDTC and TPCK) also inhibited the potentiating action of LTA. However, focal adhesion kinase (FAK) mutant and siRNA did not affect LTA-mediated IL-6 production. ...
Synovial fibroblasts isolated from human synovium. High quality synovial fibroblasts from human synovium cryopreserved and provided as frozen aliquots. Human synovial fibroblasts can be from patients with osteoarthritis, rheumatoid arthritis, or with no
Previously, using transcriptome analysis, we detected increased E2F2 expression in RA synovial tissue and confirmed this finding using Western blot analysis. We also identified E2F2 expression in RA synovial cells with immunohistochemistry [9]. In the present study, we used siRNA to inhibit E2F2 expression in RASF. We found that suppressed E2F2 expression stimulated apoptosis and deduced migration and tube-like structure formation ability in RASF. On the other hand, we observed significantly increased migration and tube-like structure formation and decreased apoptosis in RASF with transfection of E2F2 overexpressing plasmids. This observation indicates that E2F2 expression mediates RASF phenotypes and activities. Abnormal synovial fibroblast proliferation, apoptosis and migration mainly contribute to RA progression. Thus, our studies suggest that the high E2F2 expression in RA synovium contributes to the pathogenic process of this disease. E2F2 promotes cell mitosis at the transcriptional level ...
Synovial fibroblasts isolated from human synovium. High quality synovial fibroblasts from human synovium cryopreserved and provided as frozen aliquots. Human synovial fibroblasts can be from patients with osteoarthritis, rheumatoid arthritis, or with no
The mechanisms responsible for the accumulation and persistence of T cell infiltrates within the rheumatoid synovium are poorly understood. In this study we set out to explore whether the aberrant expression of chemokine receptors on synovial T cells contributes to their persistence in chronic rheumatoid synovitis. Rheumatoid synovial T cells are highly differentiated primed cells that express high levels of β1 and β2 integrins as well as the inflammatory chemokine receptors CXCR3 and CCR5 (5, 7, 8, 14). Surprisingly, they also express high levels of the constitutive chemokine receptor CXCR4, whose expression has previously been thought to be confined to unprimed CD45RA+ T cells (19, 23). Removal of T cells from the synovial microenvironment led to loss of CXCR4 expression, which was regained after exposure to autologous SF, suggesting that the synovial microenvironment directly modifies the character of infiltrating T cells in the joint.. CXCR4 is expressed on a wide variety of cells and ...
The synovial membrane in osteoarthritis (OA) often exhibits inflammatory infiltrates, but the role of T cells in these infiltrates is not known. Mouse monoclonal to TNFRSF11B versus 10 of 13 individuals with RA (not significant), whereas IL-10 transcripts were found in nearly all individuals. IL-4 and IL-5 were not detected in any individuals. The levels of IFN- and IL-2 transcripts, normalized for T-cell quantity equivalents, were not statistically different between OA and RA, but the levels of IFN-, normalized for total cell number equivalents, were reduced OA than in RA (= 0.01). Synovial membranes that indicated IL-2 and IFN- transcripts were more likely to have heavier infiltrations of T cells and cells bearing activation markers than synovial membranes that did not communicate these cytokines. The current presence of buy TG-101348 turned on T cells and TH1 cytokine transcripts in persistent joint lesions of sufferers with OA shows that T cells donate to persistent inflammation in a big ...
Rheumatoid arthritis (RA) is a persistent autoimmune disease. Fibroblast-like synoviocytes (FLS) are a key component of invasive pannus and a pathogenetic mechanism in RA. Expression of bone morphogenetic protein 3 (BMP3) mRNA is reportedly decreased in the arthritic synovium. We previously showed that BMP3 expression is significantly downregulated in the synovial tissues of RA patients and models of adjuvant-induced arthritis (AIA). In the present study, we explored the association between BMP3 and FLS migration and secretion of proinflammatory factors in RA. We found that inhibition of BMP3 expression using BMP3 siRNA increased the proinflammatory chemokines and migration of FLS stimulated with TNF-α. Inhibition of BMP3 expression also increased expression of IL-6, IL-1β, IL-17A, CCL-2, CCL-3, VCAM-1, MMP-3, and MMP-9, but not TIMP-1, in AIA and RA FLS. Correspondingly, induction of BMP3 overexpression through intra-articular injection of ad-BMP3 diminished arthritis severity in AIA rats.
It has a discontinuous surface and is not connected to a basement membrane; therefore, the synovial membrane is not an epithelium. It has many blood vessels, nerves and lymphatic vessels.. Synovial fluid (LS) is produced by the synovial membrane, which lubricates the articular surface of the joint and provides nutrients to the articular cartilage. The synovial fluid is composed mainly of hyaluronic acid, glycoproteins and transudate capillaries within the synovial membrane. ...
Nature Reviews Nephrology. fibroblast synovial cells and chondrocytes [13]. Obese osteoarthritis patients exhibit an inflammatory synovial fibroblast phenotype, which is regulated by the long non coding RNA MALAT1 November 2019 Arthritis and Rheumatology 72(4) Because we focused on the synovium, mTOR and lysophosphatidic acid were not described in greater detail, as these factors were only found to be elevated in chondrocytes/cartilage and not in synovial fibroblasts or the synovium. eCollection 2019. Bank RA Verzijl N Lafeber FP Tekoppele JM. In the past, OA was considered a disease of the cartilage only. The Smad-independent TAK-1 pathway has been shown to have profibrotic effects in regulating the expression of ECM proteins, including collagens and fibronectin [41]. OBJECTIVE: Changes in rheumatoid arthritis synovial fibroblast (RASF) gene expression are usually defined by a comparison to osteoarthritis synovial fibroblasts (OASFs). CTGF, like TGF-β, is found to be elevated in many fibrotic ...
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Biologics directed against tumor-necrosis-factor (TNF)-alpha are efficacious in the treatment of RA. However, the role of TNF receptor-1 (TNFR1) in mediating the TNFalpha effects in RA has not been elucidated and conflicting data exist in experimental arthritis models. The objective is to investigate the role of TNFR1 in the synovial lining cells (SLC) and the reticuloendothelial system (RES) during experimental arthritis. METHODS: Third generation of adenovirus serotype 5 were either injected locally in the knee joint cavity or systemically by intravenous injection into the retro-orbital venous sinus to specifically target SLC and RES, respectively. Transduction of organs was detected by immunohistochemistry of the eGFP transgene. An adenoviral vector containing a short hairpin (sh) RNA directed against TNFR1 (HpTNFR1) was constructed and functionally evaluated in vitro using a ...
Background: To examine the association between mitochondrial mutagenesis and the proinflammatory microenvironment in patients with inflammatory arthritis. Methods: Fifty patients with inflammatory arthritis underwent arthroscopy and synovial tissue biopsies, synovial fluid and clinical assessment were obtained. Fifteen patients pre/post-TNFi therapy were also recruited. Normal synovial biopsies were obtained from 10 subjects undergoing interventional arthroscopy. Macroscopic synovitis/vascularity was measured by visual analogue scale. Cell-specific markers CD3 (T cells) and CD68 (macrophages) were quantified by immunohistology. TNF?, IL-6, IFN? and IL-1? were measured in synovial fluids by MSD multiplex assays. Synovial tissue mitochondrial mutagenesis was quantified using a mitochondrial random mutation capture assay (RMCA). The direct effect of TNF? on oxidative stress and mitochondrial function was assessed in primary cultures of rheumatoid arthritis synovial fibroblast cells (RASFCs). ...
Our study focused on elucidating the in vitro effects of HA of differing molecular weights on fibroblast-like synovial cells in the face of a LPS challenge. Notably, the higher molecular weight HA product significantly reduced the morphologic change of synovial cells in vitro following a 2-hour challenge with 20 ng/ml LPS when compared with the lower molecular weight HA product (Table 1 and Figure 1). Higher molecular weight HA may preserve normal/healthy cell morphology due to a number of factors. Our results suggested that one probable mechanism to explain this finding is related to the ability of higher molecular weight HA to maintain hysteresis, compliance, and fluid exchange by reducing or dissipating stress associated with mechanical forces [42]. This facility may have enabled the fibroblast-like synovial cells in group 4 to resist contraction from the cell culture flasks when reacting to the cellular effects induced by LPS. It is also possible that pretreatment with the higher molecular ...
To investigate the effect of gentiopicrin on the expressions of inflammatory factors in human fibroblast-like synoviocytes (HFLS) and the underlying mechanism. Human fibroblast-like synoviocytes (HFLS) were cultured in vitro at 37 °C in Dulbeccos modified Eagles medium (DMEM) supplemented with 5 % fetal bovine serum (FBS) in a humidified incubator containing 5 % CO2. Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-tetrazolium bromide (MTT) assay, while real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expressions of interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) mRNAs. The expressions of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) were determined using Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IL-1ß and IL-6 in cell lysate. Treatment with 5-25 µM gentiopicrin did not significantly affect the number ...
Fibroblast-like synoviocytes (type B synoviocytes) are found in the joints, where they produce glycoproteins that comprise most of the synovial fluid, essential for joint lubrication. As the name suggests, these cells are related to fibroblasts, sharing origins and markers with them. During rheumatoid arthritis (RA), the joint becomes constantly inflamed, and, concurrently, synoviocytes acquire abnormal features and altered gene expression, contributing to tissue destruction. Although there is usually less inflammation in the joints of patients with osteoarthritis (OA), there are also signs of synoviocytes activation which may contribute to the disease progression. Arthritis research shows proinflammatory cytokines induce HFLS proliferation and stimulate their production of erosive enzymes like collagenase, aggrecanase, GM-CSF and metalloproteinases, contributing to cartilage degradation and joint destruction.We offer three types of HFLS derived from joints of healthy donors and donors
Objectives: An important feature of rheumatoid arthritis (RA) is hypoxia-driven synovial angiogenesis, but the relationship between change in vascularity, as measured by power Doppler ultrasound (PDUS), and oxygen tensions is unaddressed. Methods: Metacarpophalangeal (MCP) joint PDUS was assessed in 23 patients with RA, alongside arthroscopic synovitis and oxygen tension measurements, at baseline and 4 weeks after anti-tumour necrosis factor (TNF) inhibitors. Results: Anti-TNF reduced PDUS scores, which were negatively correlated with rise in oxygen tensions. The latter was related to good EULAR response at week 52. Conclusions: Anti-TNF results in rapid reduction in synovial blood flow, with a corresponding rise in oxygen tension most marked in EULAR good responders. ...
There is increasing evidence that TNF-alpha is a cytokine of major importance in the pathogenesis of rheumatoid arthritis. Since TNF-alpha mediates its effects via high affinity receptors, we were interested in investigating their expression and function in cells from rheumatoid tissue. Synovial fibroblasts derived from rheumatoid synovial tissue are stimulated by TNF-alpha to proliferate and release cytokines, prostaglandins, proteases and protease inhibitors. We have evaluated through which receptor stimulation of DNA synthesis and the release of the proinflammatory agents, IL-6, IL-8 and PGE2 are induced. It was found that rheumatoid synovial fibroblasts express both the p55 and p75 TNF receptor, in a ratio of 4:1. TNF-alpha-stimulated synovial fibroblast DNA synthesis and the release of IL-6, IL-8 and PGE2 was inhibited by antagonist monoclonal antibodies against either the p55 or the p75 TNF receptor, although the blockade of the p55 TNF receptor had a more potent effect than inhibition of the p75
Affiliation:徳島大学,病院,助教, Research Field:Orthopaedic surgery,Radiation science, Keywords:protease activated receptor,CT,人工股関節,IL-8,mast cell tryptase,rheumatoid arthritis,synovial fibroblast-like cell,CT,滑膜,関節液, # of Research Projects:2, # of Research Products:5
Osteoarthritis (OA) is a degenerative disorder characterized by chondrocyte apoptosis and degeneration of articular cartilage resulting in loss of mobility and pain. Inflammation plays a key role in the development and progression of OA both on the side of apoptosis and repair, while its exact role in pathogenesis has yet to be fully elucidated. Few studies have examined the cellular composition (inflammatory cells and/or progenitor cells) in the synovium of patients with pre-OA (asymptomatic with cartilage damage). Therefore, in the current study, mesenchymal progenitor cells (MPCs) and macrophages were enumerated within normal, pre-OA and OA synovium. No differences were observed between MPCs in normal vs. pre-OA, however, fewer macrophages were observed in pre-OA vs. normal synovium. Osteoarthritic synovium contained greater numbers of both MPCs and macrophages. Interestingly, the localization of MPCs and macrophages was affected by disease severity. In normal and pre-OA synovium, MPCs and
Targeting human fibroblast-like synoviocytes for RA therapies: an established in vitro cytokine-stimulated synoviocyte preclinical assay.
Looking for synovial biopsy? Find out information about synovial biopsy. examination of cells or tissues removed from a living organism. Excised material may be studied in order to diagnose disease or to confirm findings of... Explanation of synovial biopsy
The blood supply of a synovial joint comes from the arteries sharing in anastomosis around the joint. The articular and epiphyseal branches of the neighboring arteries form a periarticular arterial plexus. The articular capsule is highly innervated but avascular (lacking blood and lymph vessels), and receives nutrition from the surrounding blood supply via either the slow process of diffusion or convection, a far more efficient process.. Numerous vessels from this plexus pierce the fibrous capsule and form a rich vascular plexus in the deeper part of the synovial membrane. The blood vessels of the synovial membrane terminate around the articular margins in a fringe of looped anastomoses termed the circulus vasculosus (circulus articularis vasculosus). It supplies the capsule, synovial membrane, and the epiphyses. After epiphyseal fusion in the growth of long bones, communication between the circulosus vasculosus and the end arteries of the metaphysis is established. This minimizes the chances of ...
To examine critical interactions between juvenile idiopathic arthritis synovial fibroblasts (JFLS) and chondrocytes (Ch), and their role in bony overgrowth seen in patients with juvenile idiopathic arthritis (JIA). Control (CFLS) and JFLS were cultured in synoviocyte media containing recombinant BMP4. Ch were cultured in either CFLS or JFLS conditioned-media without stimulation. Media supernatants were analyzed by ELISA. RNA from conditioned media experiment was analyzed by ClariomS microarray. As expected, genes expressed in untreated JFLS and CFLS cultured in synoviocyte media were similar to each other and this expression differed from untreated Ch cultured in chondrocyte media. JFLS favor BMP ligand gene expression while downregulating TGFβ receptors expression. Noggin and chordin, antagonists with high affinity for BMP4, are JFLS- but not Ch-preferred regulators of BMP signaling. Compared to Ch, JFLS overexpress collagen X (COLX), a marker of chondrocyte hypertrophy. Exogenous BMP4 causes JFLS to
Studies in humans have shown that haemostatic and inflammatory pathways both play important roles in the pathogenesis of joint disease. The aim of this study was to assess mRNA expression of haemostatic and inflammatory factors in cultured equine fibroblast-like synoviocytes exposed to lipopolysaccharide (LPS), fibrinogen and thrombin. Synovial membranes were collected from metacarpo-phalangeal joints of 6 skeletally mature horses euthanized for non-orthopaedic reasons. Passage 4 fibroblast-like synoviocytes were left non-treated or treated with either 0.1 μg/ml LPS, 5 mg/ml fibrinogen or 5 U/ml thrombin and harvested at time points 0, 6, 24 and 48 h. mRNA expression of serum amyloid A (SAA), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), tissue factor (TF), plasminogen activator inhibitor 1 (PAI-1), urokinase plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and protease activator receptor 1 (PAR-1) was assessed using quantitative real time reverse transcriptase PCR
There is a growing body of evidence that implicates matrix metalloproteinases (MMPs) as major players in numerous diseased conditions. The articular cartilage degradation that is characteristic of rheumatoid arthritis (RA) is believed to be mediated by the collagenase subfamily of matrix metalloprot …
In this study, we analyzed the methylation status of human promoters in rheumatoid arthritis synovial fibroblasts (RASF). Differentially methylated genes between RASF and osteoarthritis synovial fibroblasts (OASF) were identified by methylated DNA immunoprecipitation and hybridization to human promoter tiling arrays. The methylation status was confirmed by pyrosequencing. Gene and protein expression of differentially methylated genes was evaluated with real-time PCR, Western blot, and immunohistochemistry. Chromatin immunoprecipitation was used to measure the gene promoter-associated acetylation and methylation of histones. Transcription factor-specific targets were identified with microarray and luciferase assays. We found that the transcription factor T-box transcription factor 5 (TBX5) was less methylated in rheumatoid arthritis (RA) synovium and RASF than in osteoarthritis (OA) samples. Demethylation of the TBX5 promoter in RASF and RA synovium was accompanied by higher TBX5 expression than ...
Objective. Many studies presented some evidence that EBV might play a role in the pathogenesis of rheumatoid arthritis. Still, there are conflicting reports concerning the existence of EBV in the synovial tissue of patients suffering from rheumatoid arthritis. Material and methods. Takeda et al. designed a study to detected EBV DNA is synovial tissues obtained at synovectomy or arthroplasty from 32 patients with rheumatoid arthritis (RA) and 30 control patients (no rheumatoid arthritis). In this study, the data as published by Takeda et al. were re-analysed. Results. EBV infection of human synovial tissues is a condition per quam of rheumatoid arthritis. And much more than this. There is a highly significant causal relationship between an EBV infection of human synovial tissues and rheumatoid arthritis (k= +0,546993718, p-value = 0,00001655). Conclusion. These findings suggest that EBV infection of human synovial tissues is a main cause of rheumatoid arthritis. ...
Recent work has shown that the gap junction protein connexin43 (Cx43) is upregulated in cells of the joint during osteoarthritis (OA). Here we examined if the OA-associated increase in Cx43 expression impacts the function of synovial fibroblasts by contributing to the production of catabolic and inflammatory factors that exacerbate joint destruction in arthritic disease. Using rabbit and human synovial fibroblast cell lines, we examined the effects of Cx43 overexpression and Cx43 siRNA-mediated knockdown on the gene expression of OA-associated matrix metalloproteinases (MMP1 and MMP13), aggrecanases (ADAMTS4 and ADAMTS5), and inflammatory factors (IL1, IL6 and PTGS2) by quantitative real time RT-PCR. We examined collagenase activity in conditioned media of cultured synovial cells following Cx43 overexpression. Lastly, we assessed the interplay between Cx43 and the NFκB cascade by western blotting and gene expression studies. Increasing Cx43 expression enhanced the gene expression of MMP1, MMP13,
The great success of targeted biologic therapy against rheumatoid arthritis (RA) in recent years has meant that much research has been devoted to investigating the pathophysiology of osteoarthritis (OA) in the hope of defining novel therapeutic targets. In contrast to RA, with its pannus and erosions, OA has long been thought of as a degenerative disease of cartilage, with secondary bony damage and osteophytes. But in recent years, the importance of the synovium, and in particular the synovial macrophages, in OA, has been highlighted in both in vitro and in vivo studies. This review will discuss the potential of synovial macrophages and their mediators, in particular the proinflammatory cytokines tumour necrosis factor α and interleukin-1, as potential therapeutic targets in OA.. ...
New research shows that rheumatoid arthritis synovial fibroblasts help spread destructive arthritis to other joints in the body, according to research by Lefevre and colleagues published online on the 8th November in the journal Nature Immunology. Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that can affect many tissues and organs, but mainly causes…
The phenotypic tissue immunoregulatory index in rheumatoid synovitis is locally different and varies significantly between given areas. Ectopic lymphoid follicles show normal to high T4∶T8 ratios,...
Objective: To define the expression and pattern of the synovial distribution of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1 and of TNFα and TNFβ cytokines in psoriatic arthritis (PsA), according to the synovitis duration. Methods: Cryostatic sections of the synovial membrane tissue samples were stained for the different antibodies using a standard three-stage-immunoperoxidase-labeling technique. Results: E-selectin grade of staining was higher in those patients with a shorter disease duration compared to longstanding synovitic specimens, as well as ICAM-1 expression. On the contrary a higher VCAM-1 positivity was mainly found in longstanding PsA patients. Anti-TNFa positivity was found almost in all the specimens with no difference among the two groups, while the intensity of anti-TNFβ positivity was globally higher in longstanding cases. Conclusions: Different adhesion molecules may separately participate to the synovitic process in the different phases of PsA, leading to the ...
OBJECTIVE: To characterize the bone morphogenetic protein (BMP) target cells positive for phosphorylated (P-)SMAD1/5, in rheumatoid arthritis (RA) synovium. METHODS: Synovial biopsies were obtained by needle arthroscopy. Anti-P-SMAD1/5 antibodies were used for Western blot (WB) on protein extracts from RA and normal synovium and for immunostaining of synovial biopsy sections. Positive cells were further identified by double staining for CD3, CD20, CD68, CD138, CD90, alpha smooth muscle actin (SMA), endoglin (CD105) and von Willebrand factor (VWF). In sections from early RA patients taken before and under antirheumatic treatment, the degree of inflammation and activation of the BMP pathway were quantified. RESULTS: P-SMAD1/5 protein was detected by WB in RA and to a lesser extent in normal synovium. Different P-SMAD1/5 positive cell populations were identified in RA synovium, mainly in perivascular and sublining cells. P-SMAD1/5 positive perivascular cells were alpha SMA positive and located ...
Objective The multikinase inhibitor META060 has been shown to inhibit NF-,B activation and expression of markers of inflammation. This study was undertaken to investigate the effect of META060 on biomarkers associated with bone and cartilage degradation in vitro and its antiinflammatory efficacy in vivo in both acute and chronic inflammation models. Methods Glycogen synthase kinase 3, (GSK3,),dependent ,-catenin phosphorylation was evaluated in RAW 264.7 macrophages to assess kinase inhibition. The inhibition of osteoclastogenesis and tartrate-resistant acid phosphatase (TRAP) activity was evaluated in RANKL-treated RAW 264.7 cells. The inhibition of interleukin-1, (IL-1,),mediated markers of inflammation was analyzed in human rheumatoid arthritis synovial fibroblasts (RASFs). Mice with carrageenan-induced acute inflammation and collagen-induced arthritis (CIA) were used to assess efficacy. Results META060 inhibited the activity of kinases (spleen tyrosine kinase [Syk], Brutons tyrosine kinase ...
Lunasin, a peptide with 43 amino acid residues and initially isolated and identified in soybean cotyledon, has gained extensive attention due to its anti-inflammatory and anticancer properties. However, its treatment efficacy on rheumatoid arthritis (RA) and corresponding mechanisms have not been reported. Herein, the synovial fibroblasts harvested and isolated from patients with RA were treated with lunasin at various concentrations to examine the proliferation, apoptosis status, and corresponding cell cycle of cultured RA synovial fibroblasts. Meanwhile, the underlying mechanisms of lunasin for RA treatment are explored through Western blot, real-time PCR, ELISA, and luciferase reporter assays. Lunasin significantly inhibited the proliferation and induced the apoptosis of cultured RA synovial fibroblasts. In addition, lunasin reduced the production of interleukin-6 (IL-6), IL-8, and matrix metalloproteinase-3 (MMP-3) and suppressed the activation of NF-|i|κ|/i|B in cultured RA synovial
Rheumatoid arthritis (RA) afflicts nearly 1% of the worldwide adult population. Cytokines released from immune cells cause chronic inflammation and stimulate the proliferation of synovial cells that destroy bone and cartilage of joints. But nearly 25% of RA patients do not respond to anti-cytokine therapy. This may be because synovial cell growth is also controlled by an enzyme called synoviolin. Amano et al. detected elevated synoviolin expression in the synovial tissue of RA patients. Mice overexpressing this molecule exhibited spontaneous arthropathy and a progressive synovial cell hyperplasia characteristic of RA patients. Reduced expression of synoviolin in mice correlated with protection from arthritis. This resistance was not due to an impaired cytokine response or reduced inflammatory cell infiltration, but to an increase in synovial cell apoptosis. Knockdown of synoviolin expression in rheumatoid synovial cells by RNA interference suppressed growth responses to cytokines. ...
(HealthDay)-Combined inhibition of tumor necrosis factor (TNF) ? and interleukin (IL)-17 is more effective than single blockade in cultures of human fibroblast-like synoviocytes (FLS), according to an experimental study published in the January issue of Arthritis Rheumatology. Jens A.A. F… Combined inhibition of TNF-alpha, IL-17 effective in RA model
Accumulation of senescent cells has been associated with pro-inflammatory effects with deleterious consequences in different human diseases. The purpose of this study was to analyze cell senescence in human synovial tissues (ST), and its impact on the pro-inflammatory function of synovial fibroblasts (SF). The expression of the senescence marker p16INK4a (p16) was analyzed by immunohistochemistry in rheumatoid arthritis (RA), osteoarthritis (OA), and normal ST from variably aged donors. The proportion of p16(+) senescent cells in normal ST from older donors was higher than from younger ones. Although older RA and OA ST showed proportions of senescent cells similar to older normal ST, senescence was increased in younger RA ST compared to age-matched normal ST. The percentage of senescent SA-β-gal(+) SF after 14 days in culture positively correlated with donors age. Initial exposure to H2O2 or TNFα enhanced SF senescence and increased mRNA expression of IL6, CXCL8, CCL2 and MMP3 and proteins secretion.
6. Multiplexed bead-based immunoassays used reagents purchased from Bio-Rad and R&D Systems and were analyzed on a Flexmap 3D using xPONENT software (Luminex Corp.). The levels of secreted cytokines were measured using two sets of Bio-Rad detection panels: group I 27-plex (Bio-Rad, cat. no. M500KCAF0Y) and group II 21-plex (Bio-Rad, cat. no. MF0005KMII) human cytokine panels. Levels of MMP-1, -2, and -3 were measured using the Luminex Peformance Human MMP Panel (R&D Systems, cat. nos. LMP901B, LMP901C, and LMP513B). Supernatants either were diluted 1:3 with 1xPBS / 0.05% BSA / 0.05% Tween-20 (for the Bio-Rad cytokine kits) or diluted 1:5 with Calibrator Diluent RD5-37 buffer (for the R&D Systems MMP Panel; this buffer is from the Human MMP Base Kit, cat. no. LMP000B) and assayed according to the suppliers instructions alongside a 10-point standard serial dilution to establish the dynamic range of the assay for each analyte. The immunoassay results are reported as the median fluorescent ...
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Immunohistochemical synovial tissue biomarkers are used increasingly to classify arthropathies, study their pathogenesis, and to measure disease activity in clinical trials. We have used receiver operating characteristic (ROC) analysis to quantify the discriminatory abilities of markers for common inflammatory cells (subintimal CD15, CD68, CD3, CD20, CD38, and lining CD68), proliferating cells (Ki-67) and blood vessels (von Willebrand factor, vWF) among inflammatory (chronic septic arthritis, early arthritis and rheumatoid arthritis (RA)) and degenerative arthropathies (osteoarthritis (OA) and orthopedic arthropathies) and normal synovium. Six of the eight markers distinguished accurately between RA and the degenerative arthropathies (area under the curve (AUC) 0.91-0.97), whereas subintimal CD68 (AUC 0.92) and Ki-67 (AUC 0.87) distinguished best between OA and normal synovium. Fold differences in mean expression correlated only modestly with AUCs (r2 = 0.44). Multicategory ROC analysis ranked ...
What is a synovial biopsy? Each joint in the human body contains synovial fluid. The synovial membrane secretes this fluid in the joint cavity. Lubricates joints and allows ease of movement. The synovial membrane is also the main place where inflammation occurs in joint diseases such as arthritis. Your doctor may recommend that you perform a synovial biopsy if you can not give a diagnosis based on routine measures. They may also order a biopsy if they think you might have a synovial infection… ...Read more ...
In examining the synovial membranes pertaining to the foot, as well as those connected with all other parts of the body, their relative importance to the sense under consideration, must not be measured by the superficial area any particular sac may present, but by the apparent amount of sensibility upon injury or in disease. Thus, for instance, from the few scanty opportunities the writer has had of observing indications of pain, during operations, etc., upon the foot, he is disposed to think that the calcaneo-cuboid and scaphoid synovial membranes, and the synovial sac dipping between the scaphoid and cuneiform bones, possess very little sensibility, if any; but that those connected with either extremity of the metatarsal bone of the great toe, possess considerably more. Indeed, many of the smaller synovial membranes placed in the phalangeal joints, and ako those in the tarsal and metatarsal joints, saving those connected with the great toe, appear, from the effects of continued pressure and ...
|p|Background: Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. Recent studies have shown that phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the survi
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Celastrol, a natural triterpene, exhibits potential anti-inflammatory activity in a variety of inflammatory diseases. The present study aimed to investigate its biological effect on activated fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). The primary FLSs of the synovial tissues were obtained from synovial biopsies of patients with RA. The normal human FLS line (HFLS) was used as a control. After the RA-FLSs and HFLSs were treated with or without celastrol, various approaches, including the WST-1 assay, transwell assay, real-time PCR and ELISA analysis, were performed to estimate proliferation, invasion and expression of pro-inflammatory cytokines of the RA-FLSs ...
Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not beta 2-microglobulin in human synovial cells an
four). Even though the helpful outcome of CB1 receptor antagonism in collagen-induced arthritis in mice was attributed to βtwo-receptor activation on splenocytes, numerous other mechanisms may add for the therapeutic outcomes. CB1 antagonism at sympathetic terminals bordering the synovium may need unique results depending on the magnitude of Restoration of norepinephrine stages in the joint. If βtwo signaling is restored in synovial tissue, nearby concentrations of IFN-γ and TNF may decrease, bringing about an General lower in joint destruction, synovial inflammation and pain [102, 103] (Fig. two). On the other hand, considering the fact that we shown a boost of sympathetic fibers in human synovial adipose tissue, increased norepinephrine release may well even further improve lipolysis and thereby fuel inflammation [91]. Therefore, it truly is very important to maintain norepinephrine concentrations more than a certain βtwo activation threshold in the synovium, which might only be attained ...
The aetiology of rheumatoid arthritis is still unknown. A genetic disorder triggered by an environmental factor may induce a defective immune response, mostly in the synovial membrane.
Wittenberg, HR; Kleemeyer, K; Peskar, BM; Peskar, BA Effect of sulfasalazine and its metabolites on prostaglandin and leukotriene liberation from human synovial tissue ...
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DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry ...