Receptor protein tyrosine phosphatase alpha enhances rheumatoid synovial fibroblast signaling and promotes arthritis in mice

NARCIS (Netherlands)

Stanford, Stephanie M; Svensson, Mattias N D; Sacchetti, Cristiano; Pilo, Caila A; Wu, Dennis J; Kiosses, William B; Hellvard, Annelie; Bergum, Brith; Aleman Muench, German R; Elly, Christian; Liu, Yun-Cai; den Hertog, Jeroen; Elson, Ari; Sap, Jan; Mydel, Piotr; Boyle, David L; Corr, Maripat; Firestein, Gary S; Bottini, Nunzio

2016-01-01

OBJECTIVE: During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the joint extracellular matrix. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to RA FLS anomalous behavior. The receptor

Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

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Shuo Liu

Full Text Available Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases

Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

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Liu, Shuo; Niger, Corinne; Koh, Eugene Y; Stains, Joseph P

2015-01-01

Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs) could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis)-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases like

CD14-negative isolation enhances chondrogenesis in synovial fibroblasts.

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Bilgen, Bahar; Ren, Yuexin; Pei, Ming; Aaron, Roy K; Ciombor, Deborah McK

2009-11-01

Synovial membrane has been shown to contain mesenchymal stem cells. We hypothesized that an enriched population of synovial fibroblasts would undergo chondrogenic differentiation and secrete cartilage extracellular matrix to a greater extent than would a mixed synovial cell population (MSCP). The optimum doses of transforming growth factor beta 1 (TGF-beta1) and insulin-like growth factor 1 (IGF-1) for chondrogenesis were investigated. CD14-negative isolation was used to obtain a porcine cell population enriched in type-B synovial fibroblasts (SFB) from an MSCP. The positive cell surface markers in SFB were CD90, CD44, and cadherin-11. SFB and MSCP were cultured in the presence of 20 ng/mL TGF-beta1 for 7 days, and SFB were demonstrated to have higher chondrogenic potential. Further dose-response studies were carried out using the SFB cells and several doses of TGF-beta1 (2, 10, 20, and 40 ng/mL) and/or IGF-1 (1, 10, 100, and 500 ng/mL) for 14 days. TGF-beta1 supplementation was essential for chondrogenesis and prevention of cell death, whereas IGF-1 did not have a significant effect on the SFB cell number or glycosaminoglycan production. This study demonstrates that the CD14-negative isolation yields an enhanced cell population SFB that is more potent than MSCP as a cell source for cartilage tissue engineering.

TLR3 Ligand Poly(I:C Exerts Distinct Actions in Synovial Fibroblasts When Delivered by Extracellular Vesicles

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Mojca Frank-Bertoncelj

2018-01-01

Full Text Available Extracellular vesicles (EV can modulate the responses of cells to toll-like receptor (TLR ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis. We have used as model the effects on RA SFs, of EV released from monocyte U937 cells and peripheral blood mononuclear cells upon stimulation with Poly(I:C, a synthetic analog of dsRNA. We show that EV released from unstimulated cells and Poly(I:C-stimulated U937 cells [Poly(I:C EV] differ in size but bind similar amounts of Annexin V and express comparable levels of MAC-1, the receptor for dsRNA, on the vesicular membranes. Specifically, Poly(I:C EV contain or associate with Poly(I:C and at least partially protect Poly(I:C from RNAse III degradation. Poly(I:C EV shuttle Poly(I:C to SFs and reproduce the proinflammatory and antiviral gene responses of SFs to direct stimulation with Poly(I:C. Poly(I:C EV, however, halt the death receptor-induced apoptosis in SFs, thereby inverting the proapoptotic nature of Poly(I:C. These prosurvival effects sharply contrast with the high toxicity of cationic liposome-delivered Poly(I:C and may reflect the route of Poly(I:C delivery via EV or the fine-tuning of Poly(I:C actions by molecular cargo in EV. The demonstration that EV may safeguard extracellular dsRNA and allow dsRNA to exert antiapoptotic effects on SFs highlights the potential of EV to amplify the pathogenicity of dsRNA in arthritis beyond inflammation (by concurrently enhancing the

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

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Hirota, Keiji; Hashimoto, Motomu; Ito, Yoshinaga; Matsuura, Mayumi; Ito, Hiromu; Tanaka, Masao; Watanabe, Hitomi; Kondoh, Gen; Tanaka, Atsushi; Yasuda, Keiko; Kopf, Manfred; Potocnik, Alexandre J; Stockinger, Brigitta; Sakaguchi, Noriko; Sakaguchi, Shimon

2018-06-19

Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical Hypoxia Brings to Light Altered Autocrine Sphingosine-1-Phosphate Signalling in Rheumatoid Arthritis Synovial Fibroblasts

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Chenqi Zhao

2015-01-01

Full Text Available Emerging evidence suggests a role for sphingosine-1-phosphate (S1P in various aspects of rheumatoid arthritis (RA pathogenesis. In this study we compared the effect of chemical hypoxia induced by cobalt chloride (CoCl2 on the expression of S1P metabolic enzymes and cytokine/chemokine secretion in normal fibroblast-like synoviocytes (FLS and RAFLS. RAFLS incubated with CoCl2, but not S1P, produced less IL-8 and MCP-1 than normal FLS. Furthermore, incubation with the S1P2 and S1P3 receptor antagonists, JTE-013 and CAY10444, reduced CoCl2-mediated chemokine production in normal FLS but not in RAFLS. RAFLS showed lower levels of intracellular S1P and enhanced mRNA expression of S1P phosphatase 1 (SGPP1 and S1P lyase (SPL, the enzymes that are involved in intracellular S1P degradation, when compared to normal FLS. Incubation with CoCl2 decreased SGPP1 mRNA and protein and SPL mRNA as well. Inhibition of SPL enhanced CoCl2-mediated cytokine/chemokine release and restored autocrine activation of S1P2 and S1P3 receptors in RAFLS. The results suggest that the sphingolipid pathway regulating the intracellular levels of S1P is dysregulated in RAFLS and has a significant impact on cell autocrine activation by S1P. Altered sphingolipid metabolism in FLS from patients with advanced RA raises the issue of synovial cell burnout due to chronic inflammation.

MiR-338-5p Promotes Inflammatory Response of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Targeting SPRY1.

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Yang, Yan; Wang, Yanfeng; Liang, Qingwei; Yao, Lutian; Gu, Shizhong; Bai, Xizhuang

2017-08-01

Our purpose is to study the roles of microRNA-338-5p (miR-338-5p) on the proliferation, invasion, and inflammatory response of fibroblast-like synoviocytes (SFs) in rheumatoid arthritis patients by regulating SPRY1. The target relationship between miR-338-5p and SPRY1 was validated through luciferase reporter system. The expression of miR-338-5p and SPRY1 in synovial tissues and synovial cells were detected using RT-PCR and western blot. The mimics and inhibitors of miR-338-5p were transfected into SFs. MTT, Transwell, and ELISA assays were used to analyze cell proliferation, invasiveness, and the secreted extracellular pro-inflammatory cytokines (such as IL-1a, IL-6, COX2) levels of SFs. MiR-338-5p was highly expressed in rheumatoid arthritis tissues and cells, and directly down-regulated the expression of SPRY1 in the SFs of rheumatoid arthritis patients. Cell proliferation, invasiveness and the expression level of pro-inflammatory cytokines in synovial cells increased after the transfection of miR-338-5p mimics, while the proliferation, invasion and expression level of pro-inflammatory cytokines decreased after the transfection of miR-338-5p inhibitors. In conclusion,miR-338-5p promoted the proliferation, invasion and inflammatory reaction in SFs of rheumatoid arthritis by directly down-regulating SPRY1 expression. J. Cell. Biochem. 118: 2295-2301, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature

NARCIS (Netherlands)

Gerlag, D. M.; Borges, E.; Tak, P. P.; Ellerby, H. M.; Bredesen, D. E.; Pasqualini, R.; Ruoslahti, E.; Firestein, G. S.

2001-01-01

Because angiogenesis plays a major role in the perpetuation of inflammatory arthritis, we explored a method for selectively targeting and destroying new synovial blood vessels. Mice with collagen-induced arthritis were injected intravenously with phage expressing an RGD motif. In addition, the RGD

Receptor Protein Tyrosine Phosphatase α-Mediated Enhancement of Rheumatoid Synovial Fibroblast Signaling and Promotion of Arthritis in Mice

NARCIS (Netherlands)

Stanford, Stephanie M; Svensson, Mattias N D; Sacchetti, Cristiano; Pilo, Caila A; Wu, Dennis J; Kiosses, William B; Hellvard, Annelie; Bergum, Brith; Muench, German R Aleman; Elly, Christian; Liu, Yun-Cai; den Hertog, Jeroen; Elson, Ari; Sap, Jan; Mydel, Piotr; Boyle, David L; Corr, Maripat; Firestein, Gary S; Bottini, Nunzio

OBJECTIVE: During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the extracellular matrix of the joint. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to the anomalous behavior of RA FLS.

The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast

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Yi-Te Chen

2014-01-01

Full Text Available Osteoarthritis (OA belongs to a group of degenerative diseases. Synovial inflammation, cartilage abrasion, and subchondral sclerosis are characteristics of OA. Researchers do not fully understand the exact etiology of OA. However, matrix metalloproteinases (MMPs, which are responsible for cartilage matrix degradation, play a pivotal role in the progression of OA. Amphiregulin (AREG binds to the EGF receptor (EGFR and activates downstream proteins. AREG is involved in a variety of pathological processes, such as the development of tumors, inflammatory diseases, and rheumatoid arthritis. However, the relationship between AREG and MMP-13 in OA synovial fibroblasts (SFs remains unclear. We investigated the signaling pathway involved in AREG-induced MMP-13 production in SFs. AREG caused MMP-13 production in a concentration- and time-dependent manner. The results of using pharmacological inhibitors and EGFR siRNA to block EGFR revealed that the EGFR receptor was involved in the AREG-mediated upregulation of MMP-13. AREG-mediated MMP-13 production was attenuated by PI3K and Akt inhibitors. The stimulation of cells by using AREG activated p65 phosphorylation and p65 translocation from the cytosol to the nucleus. Our results provide evidence that AREG acts through the EGFR and activates PI3K, Akt, and finally NF-kappaB on the MMP-13 promoter, thus contributing to cartilage destruction during osteoarthritis.

Gross and histopathological findings in synovial membranes of pigs with experimentally induced Mycoplasma hyosynoviae arthritis

DEFF Research Database (Denmark)

Hagedorn-Olsen, T.; Basse, A.; Jensen, Tim Kåre

1999-01-01

or contact exposure with M. hyosynoviae induced arthritis in 13- to 17-week-old pigs. The acute to subacute arthritis was characterized by increased amounts of serohaemorrhagic, serofibrinous or mahogany coloured synovial fluid combined with edema and hyperaemia, followed by yellow to brownish discoloration...... and moderate villous proliferation of the synovial membrane. In the chronic phase moderate fibrosis was seen, but no periarticular or articular cartilage involvement. The acute to subacute histopathological characteristics were edema, hyperaemia, variable hyperplasia of synovial lining cells, increased density...... of subsynovial cell populations, diffuse and perivascular infiltration with lymphocytes, plasma cells and macrophage-like cells, fibrinous material, mild to moderate villous hypertrophy and mild to moderate fibrosis in chronic cases. The morphogenetic changes during the course of the infection may be described...

Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation

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Katsuya Kobayashi

2007-01-01

Full Text Available A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA. Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4 inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-α and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

Administration of PDE4 inhibitors suppressed the pannus-like inflammation by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

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Kobayashi, Katsuya; Suda, Toshio; Manabe, Haruhiko; Miki, Ichiro

2007-01-01

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1beta, TNF-alpha, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-alpha and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

Ablation of synovial pannus using microbubble-mediated ultrasonic cavitation in antigen-induced arthritis in rabbits.

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Qiu, Li; Jiang, Yong; Zhang, Lingyan; Wang, Lei; Luo, Yan

2012-12-01

To investigate the ablative effectiveness of microbubble-mediated ultrasonic cavitation for treating synovial pannus and to determine a potential mechanism using the antigen-induced arthritis model (AIA). Ultrasonic ablation was performed on the knee joints of AIA rabbits using optimal ultrasonic ablative parameters. Rabbits with antigen-induced arthritis were randomly assigned to 4 groups: (1) the ultrasound (US) + microbubble group; (2) the US only group; (3) the microbubble only group, and (4) the control group. At 1 h and 14 days after the first ablation, contrast-enhanced ultrasonography (CEUS) monitoring and pathology synovitis score were used to evaluate the therapeutic effects. Synovial necrosis and microvascular changes were also measured. After the ablation treatment, the thickness of synovium and parameters of time intensity curve including derived peak intensity and area under curve were measured using CEUS, and the pathology synovitis score in the ultrasound + microbubble group was significantly lower than that found in the remaining groups. No damage was observed in the surrounding normal tissues. The mechanism underlying the ultrasonic ablation was related to microthrombosis and microvascular rupture that resulted in synovial necrosis. The results suggest that microbubble-mediated ultrasonic cavitation should be applied as a non-invasive strategy for the treatment of synovial pannus in arthritis under optimal conditions.

Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome: differential diagnosis of septic arthritis by regular detection of exceedingly high synovial cell counts.

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Löffler, W; Lohse, P; Weihmayr, T; Widenmayer, W

2017-08-01

Pyogenic arthritis, pyoderma gangrenosum and acne syndrome was diagnosed in a 42-year-old patient, after an unusual persistency of high synovial cell counts had been noticed. Clinical peculiarities and problems with diagnosing septic versus non-septic arthritis are discussed.

In vitro and in vivo spin echo diffusion imaging characteristics of synovial fluid: potential non-invasive differentiation of inflammatory and degenerative arthritis

International Nuclear Information System (INIS)

Eustace, S.; DiMasi, M.; Adams, J.; Ward, R.; Caruthers, S.; McAlindon, T.

2000-01-01

Objective. This study was undertaken to analyse the diffusion characteristics of synovial fluid in degenerative and inflammatory arthropathies.Design and patients. Ten in vitro specimens of synovial fluid from patients with both degenerative and inflammatory arthropathy were studied at body temperature with a navigator-corrected spin echo diffusion sequence (B values 0-512 s/mm 2 ), on a Philips 1.5-T Gyroscan. Subsequently synovial fluid from knee joint effusions of 25 patients (10 patients with osteoarthritis, 10 patients with effusions following trauma and 5 patients with effusions secondary to inflammatory arthritis) was evaluated with the same navigator-corrected spin echo diffusion sequence.Results. Both in vitro and in vivo study demonstrated decreased diffusion in patients with effusions secondary to degenerative joint disease (less than 2.40 x 10 -5 cm 2 /s) relative to patients with effusions accompanying knee trauma (greater than 2.75 x 10 -5 cm 2 /s) and inflammatory arthritis (in vitro and in vivo greater than 3.00 x 10 -5 cm 2 /s).Conclusion. Synovial fluid in degenerative arthritis shows less diffusion or free water movement than synovial fluid in inflammatory arthritis. Diffusion characteristics of synovial fluid may be used to predict the nature of the underlying form of arthritis in patients presenting with knee joint effusions. (orig.)

Retroviral gene transfer of an antisense construct against membrane type 1 matrix metalloproteinase reduces the invasiveness of rheumatoid arthritis synovial fibroblasts.

Science.gov (United States)

Rutkauskaite, Edita; Volkmer, Dagmar; Shigeyama, Yukio; Schedel, Jörg; Pap, Geza; Müller-Ladner, Ulf; Meinecke, Ingmar; Alexander, Dorothea; Gay, Renate E; Drynda, Susanne; Neumann, Wolfram; Michel, Beat A; Aicher, Wilhelm K; Gay, Steffen; Pap, Thomas

2005-07-01

Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed prominently in rheumatoid arthritis synovial fibroblasts (RASFs), but the specific contribution of MT1-MMP to fibroblast-mediated destruction of articular cartilage is incompletely understood. This study used gene transfer of an antisense expression construct to assess the effects of MT1-MMP inhibition on the invasiveness of RASFs. Retroviral gene transfer of a pLXIN vector-based antisense RNA expression construct (MT1-MMPalphaS) to MT1-MMP was used to stably transduce RASFs. Levels of MT1-MMP RNA and protein were determined by quantitative polymerase chain reaction, Western blotting, and immunocytochemistry in MT1-MMPalphaS-transduced RASFs as well as in control cells, with monitoring for 60 days. The effects of MT1-MMPalphaS on the invasiveness of RASFs were analyzed in the SCID mouse co-implantation model of RA. MT1-MMPalphaS-transduced RASFs produced high levels of antisense RNA that exceeded endogenous levels of MT1-MMP messenger RNA by 15-fold and resulted in a down-regulation of MT1-MMP at the protein level. Inhibition of MT1-MMP production was maintained for 60 days and significantly reduced the invasiveness of RASFs in the SCID mouse model. Whereas prominent invasion into cartilage by non-transduced and mock-transduced RASFs was observed (mean invasion scores 3.0 and 3.1, respectively), MT1-MMPalphaS-transduced cells showed only moderate invasiveness (mean invasion score 1.8; P < 0.05). The data demonstrate that an antisense RNA expression construct against MT1-MMP can be generated and expressed in RASFs for at least 60 days. Inhibition of MT1-MMP significantly reduces the cartilage degradation by RASFs.

Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis

NARCIS (Netherlands)

Choi, Ivy Y.; Karpus, Olga N.; Turner, Jason D.; Hardie, Debbie; Marshall, Jennifer L.; de Hair, Maria J. H.; Maijer, Karen I.; Tak, Paul P.; Raza, Karim; Hamann, Jörg; Buckley, Christopher D.; Gerlag, Danielle M.; Filer, Andrew

2017-01-01

Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied. ST from 56 patients included

Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation

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Umar, Sadiq; Hedaya, Omar; Singh, Anil K.; Ahmed, Salahuddin, E-mail: salah.ahmed@wsu.edu

2015-09-15

Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced by monocytes/macrophage that plays a pathological role in rheumatoid arthritis (RA). In this study, we investigate the effect of thymoquinone (TQ), a phytochemical found in Nigella sativa, in regulating TNF-α-induced RA synovial fibroblast (RA-FLS) activation. Treatment with TQ (1–5 μM) had no marked effect on the viability of human RA-FLS. Pre-treatment of TQ inhibited TNF-α-induced interleukin-6 (IL-6) and IL-8 production and ICAM-1, VCAM-1, and cadherin-11 (Cad-11) expression in RA-FLS (p < 0.01). Evaluation of the signaling events showed that TQ inhibited TNF-α-induced phospho-p38 and phospho-JNK expression, but had no inhibitory effect on NF-κB pathway, in RA-FLS (p < 0.05; n = 4). Interestingly, we observed that selective down-regulation of TNF-α-induced phospho-p38 and phospho-JNK activation by TQ is elicited through inhibition of apoptosis-regulated signaling kinase 1 (ASK1). Furthermore, TNF-α selectively induced phosphorylation of ASK1 at Thr845 residue in RA-FLS, which was inhibited by TQ pretreatment in a dose dependent manner (p < 0.01). Pre-treatment of RA-FLS with ASK1 inhibitor (TC ASK10), blocked TNF-α induced expression of ICAM-1, VCAM-1, and Cad-11. Our results suggest that TNF-α-induced ASK1-p38/JNK pathway is an important mediator of cytokine synthesis and enhanced expression of adhesion molecule in RA-FLS and TQ, by selectively inhibiting this pathway, may have a potential therapeutic value in regulating tissue destruction observed in RA. - Highlights: • Evolving evidence suggests that ASK1 plays a central role in rheumatic arthritis (RA). • TNF-α activates ASK1, which regulate downstream signaling through JNK/p38 activation in RA-FLS. • ASK1 may be used as a potential therapeutic target in RA. • Thymoquinone was able to selectively inhibit TNF-α-induced phosphorylation of ASK1 in RA-FLS. • Thymoquinone might serve as a potential small

Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis

OpenAIRE

Bianchessi, Marta; Chen, Yuwen; Durgam, Sushmitha; Pondenis, Holly; Stewart, Matthew

2015-01-01

Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP) cells in equine synovial fluid (SF) and to determine the effect of fibroblast growth factor 2 (FGF-2) on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU) assa...

Chlamydia pecorum in Joint Tissue and Synovial Fluid of a Koala ( Phascolarctos cinereus) with Arthritis.

Science.gov (United States)

Burnard, Delaney; Gillett, Amber; Polkinghorne, Adam

2018-03-02

A small number of koalas ( Phascolarctos cinereus) presented to wildlife hospitals in Queensland, Australia, with signs of arthritis in one or more joints. Molecular analysis identified Chlamydia pecorum in the tarsal tissue and synovial fluid of an affected joint of a koala, suggesting that in addition to livestock, C. pecorum has the potential to cause arthritis in the koala.

Synovial tissue research

DEFF Research Database (Denmark)

Orr, Carl; Sousa, Elsa; Boyle, David L

2017-01-01

The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable...... easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly...... diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis...

CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis

NARCIS (Netherlands)

Karpus, Olga N.; Kiener, Hans P.; Niederreiter, Birgit; Yilmaz-Elis, A. Seda; van der Kaa, Jos; Ramaglia, Valeria; Arens, Ramon; Smolen, Josef S.; Botto, Marina; Tak, Paul P.; Verbeek, J. Sjef; Hamann, Jörg

2015-01-01

CD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence. Synovial tissue,

Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid.

Science.gov (United States)

Anitua, E; Sanchez, M; De la Fuente, M; Zalduendo, M M; Orive, G

2012-09-01

Cell migration plays an essential role in development, wound healing, and tissue regeneration. Plasma rich in growth factors (PRGF-Endoret) technology offers a potential source of growth factors involved in tissue regeneration. Here, we evaluate the potential of PRGF-Endoret over tendon cells and synovial fibroblasts migration and study whether the combination of this autologous technology with hyaluronic acid (HA) improves the effect and potential of the biomaterials over the motility of both types of fibroblasts. Migration of primary tendon cells and synovial fibroblasts after culturing with either PRGF or PPGF (plasma poor in growth factors) at different doses was evaluated. Furthermore, the migratory capacity induced by the combination of PPGF and PRGF with HA was tested. PPGF stimulated migration of both types of cells but this effect was significantly higher when PRGF was used. Tendon cells showed an increase of 212% in migratory ability when HA was combined with PPGF and of 335% in the case of HA + PRGF treatment compared with HA alone. PRGF-Endoret stimulates migration of tendon cells and synovial fibroblasts and improves the biological properties of HA.

[Destruction of synovial pannus of antigen-induced arthritis by ultrasonic cavitation in rabbits].

Science.gov (United States)

Zhang, Ling-yan; Qiu, Li; Wang, Lei; Lin, Ling; Wen, Xiao-rong

2011-11-01

To optimize the conditions of ultrasonic irradiation and microbubble of ultrasound cavitation on destruction of synovial pannus of antigen-induced arthritis (AIA) in rabbits. Antigen-induced arthritis was successfully induced on bilateral knee joints of 85 rabbits. Each 10 AIA rabbits were divided into two groups to compare various peak negative pressures, different ultrasonic pulse durations, various pulse repetition frequencies, different irradiance duration, different dosages of microbubble contrast agents, different ultrasonic irradiance times. With intravenous infusion of Sonovue to the rabbits, ultrasonic irradiance was performed on the right knee joint using the above condition of ultrasound cavitation. At the day 1 after ultrasonic irradiance, MRI and pathological examination were employed to evaluate the optimal conditions. The optimal parameters and conditions for ultrasonic irradiance included intermittent ultrasonic application (in 6 s intervals), 0.6 mL/kg of microbubble contrast agent, 4.6 MPa of ultrasonic peak negative pressure, 100 cycles of pulse duration, 50 Hz of pulse repetition frequency, 5 min of ultrasonic duration, 0.6 mL/kg of dosages of microbubble contrast agents and multi-sessional ultrasonic irradiance. After the ultrasonic irradiance, the thickness of right knee synovium measured by MRI was thinner than that of left knee and synovial necrosis was confirmed by the pathological finding. Under optimal ultrasonic irradiation and microbubble conditions, ultrasonic cavitation could destroy synovial pannus of AIA in rabbits.

Increased synovial tissue NF-kappa B1 expression at sites adjacent to the cartilage-pannus junction in rheumatoid arthritis.

NARCIS (Netherlands)

Benito, M.J.; Murphy, E.P.; Berg, W.B. van den; Fitzgerald, O.; Bresnihan, B.

2004-01-01

OBJECTIVE: To compare the expression of the Rel/NF-kappa B subunits, NF-kappa B1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage-pannus junction (CPJ) in patients with inflammatory arthritis. METHODS: Synovial tissue was selected

Hip Synovial Fluid Cell Counts in Children From a Lyme Disease Endemic Area.

Science.gov (United States)

Dart, Arianna H; Michelson, Kenneth A; Aronson, Paul L; Garro, Aris C; Lee, Thomas J; Glerum, Kimberly M; Nigrovic, Peter A; Kocher, Mininder S; Bachur, Richard G; Nigrovic, Lise E

2018-05-01

Patients with septic hip arthritis require surgical drainage, but they can be difficult to distinguish from patients with Lyme arthritis. The ability of synovial fluid white blood cell (WBC) counts to help discriminate between septic and Lyme arthritis of the hip has not been investigated. We assembled a retrospective cohort of patients ≤21 years of age with hip monoarticular arthritis and a synovial fluid culture obtained who presented to 1 of 3 emergency departments located in Lyme disease endemic areas. Septic arthritis was defined as a positive synovial fluid culture result or synovial fluid pleocytosis (WBC count ≥50 000 cells per µL) with a positive blood culture result. Lyme arthritis was defined as positive 2-tiered Lyme disease serology results and negative synovial fluid bacterial culture results. All other patients were classified as having other arthritis. We compared median synovial fluid WBC counts by arthritis type. Of the 238 eligible patients, 26 (11%) had septic arthritis, 32 (13%) had Lyme arthritis, and 180 (76%) had other arthritis. Patients with septic arthritis had a higher median synovial fluid WBC count (126 130 cells per µL; interquartile range 83 303-209 332 cells per µL) than patients with Lyme arthritis (53 955 cells per µL; interquartile range 33 789-73 375 cells per µL). Eighteen patients (56%) with Lyme arthritis had synovial fluid WBC counts ≥50 000 cells per µL. Of the 94 patients who underwent surgical drainage, 13 were later diagnosed with Lyme arthritis. In Lyme disease endemic areas, synovial fluid WBC counts cannot always help differentiate septic from Lyme arthritis. Rapid Lyme diagnostics could help avoid unnecessary operative procedures in patients with Lyme arthritis. Copyright © 2018 by the American Academy of Pediatrics.

Synovial tissue hypoxia and inflammation in vivo.

LENUS (Irish Health Repository)

Ng, C T

2012-02-01

INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic\\/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.

LENUS (Irish Health Repository)

Connolly, Mary

2010-06-01

Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte\\/monocyte migration assays, invasion assays, and adhesion assays with or without anti-MCP-1\\/anti-IL-8. NF-kappaB was examined using a specific inhibitor and Western blotting. An RA synovial\\/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil-transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti-IL-8 or anti-MCP-1. A-SAA-induced chemokine expression was mediated through NF-kappaB in RA explants (p < 0.05). Finally, in the RA synovial\\/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.

Anti-xanthine oxidase antibodies in sera and synovial fluid of patients with rheumatoid arthritis and other joint inflammations

International Nuclear Information System (INIS)

Arrar, L.; Hanachi, N.; Rouba, K.; Charef, N.; Khennouf, S.; Baghiani, A.

2008-01-01

Objective was to study anti-bovine milk xanthine oxidoreductase XOPR antibody levels in synovial fluid as well as in serum of patients suffering from rheumatoid affections to assess a possible correlation between antibody titres and severity of disease. Sera and synovial fluids were collected from volunteer donors at Setif University Hospital, Setif, Algeria from 2001-2007 with the consent of patients. Human IgG and IgM levels of free and bound anti-bovine milk XOR antibodies were determined using bovine XOR as antigen, with enzyme-linked immunosorbent assay ELISA. Serum IgG anti-bovine milk XOR titres in 30 healthy normal subjects 2.74+-2.31 microgram/mL are in agreement with that reported in the literature. Immunoglobulin G and IgM anti-bovine milk XOR antibody titres were found to be significantly higher in serum from patients with rheumatoid arthritis RA and latex positives subjects. Synovial IgM antibody titres to bovine XOR were found to be significantly higher in rheumatoid arthritis patients compared to patients with other joint inflammations. In rheumatoid arthritis patients, high concentrations of antibodies against XOR were noticed. These antibodies may play a major role in RA by inhibiting both xanthine and NADH oxidase activities of XOR. They may also play a key role in eliminating XOR from serum and synovial fluid positive role but unfortunately, immune complex formation could also activate complement and participate in self maintenance of inflammation. (author)

Hairy polyelectrolyte brushes-grafted thermosensitive microgels as artificial synovial fluid for simultaneous biomimetic lubrication and arthritis treatment.

Science.gov (United States)

Liu, Guoqiang; Liu, Zhilu; Li, Na; Wang, Xiaolong; Zhou, Feng; Liu, Weimin

2014-11-26

We report the fabrication of poly(3-sulfopropyl methacrylate potassium salt) (PSPMK) brushes grafted poly(N-isopropylacrylamide) (PNIPAAm) microgels and their potential as artificial synovial fluid for biomimetic aqueous lubrication and arthritis treatment. The negatively charged PSPMK brushes and thermosensitive PNIPAAm microgels play water-based hydration lubrication and temperature-triggered drug release, respectively. Under soft friction pairs, an ultralow coefficient of friction was achieved, while the hairy thermosensitive microgels showed a desirable temperature-triggered drugs release performance. Such a soft charged hairy microgel offers great possibility for designing intelligent synovial fluid. What is more, the combination of lubrication and drug loading capabilities enables the large clinical potential of novel soft hairy nanoparticles as synthetic joint lubricant fluid in arthritis treatment.

Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo.

Science.gov (United States)

Xiang, Xi; Tang, Yuanjiao; Leng, Qianying; Zhang, Lingyan; Qiu, Li

2016-02-01

The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (Ppannus of an AIA model. Thus, this could become a safe and effective non-viral gene transfection procedure for arthritis therapy. Copyright © 2015 Elsevier B.V. All rights

Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts.

Science.gov (United States)

Fechtner, Sabrina; Singh, Anil; Chourasia, Mukesh; Ahmed, Salahuddin

2017-08-15

In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea. Copyright © 2017. Published by Elsevier Inc.

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis

Science.gov (United States)

Boyle, D L; Soma, K; Hodge, J; Kavanaugh, A; Mandel, D; Mease, P; Shurmur, R; Singhal, A K; Wei, N; Rosengren, S; Kaplan, I; Krishnaswami, S; Luo, Z; Bradley, J; Firestein, G S

2015-01-01

Objective Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated. Methods A randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699). Results Tofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (pTofacitinib significantly decreased plasma CXCL10 (pTofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response. Trial registration number NCT00976599. PMID:25398374

Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood

NARCIS (Netherlands)

van Baarsen, Lisa G. M.; Wijbrandts, Carla A.; Timmer, Trieneke C. G.; van der Pouw Kraan, Tineke C. T. M.; Tak, Paul P.; Verweij, Cornelis L.

2010-01-01

OBJECTIVE: To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. METHODS: Gene expression analysis using complementary DNA microarrays was applied on paired

Analysis of the cell infiltrate and expression of matrix metalloproteinases and granzyme B in paired synovial biopsy specimens from the cartilage-pannus junction in patients with RA

NARCIS (Netherlands)

Smeets, T. J.; Kraan, M. C.; Galjaard, S.; Youssef, P. P.; Smith, M. D.; Tak, P. P.

2001-01-01

Examination of synovial tissue (ST) obtained at surgery because of end stage destructive rheumatoid arthritis (RA) showed that macrophages and fibroblasts are the major cell types at the cartilage-pannus junction (CPJ). This study aimed at defining the cell infiltrate and mediators of joint

Curcumin attenuates inflammatory response in IL-1beta-induced human synovial fibroblasts and collagen-induced arthritis in mouse model.

Science.gov (United States)

Moon, Dong-Oh; Kim, Mun-Ok; Choi, Yung Hyun; Park, Yung-Min; Kim, Gi-Young

2010-05-01

Curcumin, a major component of turmeric, has been shown to exhibit anti-oxidant and anti-inflammatory activities. The present study was performed to determine whether curcumin is efficacious against both collagen-induced arthritis (CIA) in mice and IL-1beta-induced activation in fibroblast-like synoviocytes (FLSs). DBA/1 mice were immunized with bovine type II collagen (CII) and treated with curcumin every other day for 2weeks after the initial immunization. For arthritis, we evaluated the incidence of disease and used an arthritis index based on paw thickness. In vitro proliferation of CII- or concanavalin A-induced splenic T cells was examined using IFN-gamma production. Pro-inflammatory cytokines TNF-alpha and IL-1beta were examined in the mouse ankle joint and serum IgG1 and IgG2a isotypes were analyzed. The expression levels of prostaglandin E(2) (PGE(2)), cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) in human FLSs were also determined. The results showed that compared with untreated CIA mice, curcumin-treated mice downregulated clinical arthritis score, the proliferation of splenic T cells, expression levels of TNF-alpha and IL-1beta in the ankle joint, and expression levels of IgG2a in serum. Additionally, by altering nuclear factor (NF)-kappaB transcription activity in FLSs, curcumin inhibited PGE(2) production, COX-2 expression, and MMP secretion. These results suggest that curcumin can effectively suppress inflammatory response by inhibiting pro-inflammatory mediators and regulating humoral and cellular immune responses. Copyright 2010 Elsevier B.V. All rights reserved.

Lactate and T2 measurements of synovial aspirates at 1.5 T: differentiation of septic from non-septic arthritis

International Nuclear Information System (INIS)

Wiener, Edzard; Zanetti, Marco; Hodler, Juerg; Pfirrmann, Christian W.A.

2008-01-01

The aim of this study was to differentiate septic from non-septic arthritis by measuring lactate concentration with 1 H magnetic resonance spectroscopy (HMRS) and by estimating total protein content with the assessment of T 2 values. In 30 patients with acute arthritis, synovial fluid was aspirated. Lactate concentrations were analyzed with single voxel HMRS at 1.5 T. T 2 relaxation times were mapped with a multi-spin echo sequence. All samples underwent microbiological testing and routine laboratory analysis to quantify lactate concentration and total protein content. Values obtained in septic and non-septic arthritis were compared with a Mann-Whitney U test. Synovial fluid from patients with septic arthritis (n=10) had higher concentrations of lactate (11.4 ± 4.0 mmol/L) and higher total protein content (51.8 ± 10.7 g/L) than fluid obtained in non-septic arthritis (n=20; 5.2±1.1 mmol/L and 40.4±6.9 g/L, respectively, p 2 relaxation times (as an indicator of total protein content) were moderately correlated to laboratory-confirmed lactate concentration (r 2 =0.71) and total protein content (r 2 =0.73). Markedly increased lactate concentrations (>6 mmol/L) in combination with low T 2 values ( 2 may be of value in the differentiation of septic from non-septic arthritis. (orig.)

Dynamic automated synovial imaging (DASI) for differential diagnosis of rheumatoid arthritis

Science.gov (United States)

Grisan, E.; Raffeiner, B.; Coran, A.; Rizzo, G.; Ciprian, L.; Stramare, R.

2014-03-01

Inflammatory rheumatic diseases are leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity and increased mortality. The gold-standard for diagnosing and differentiating arthritis is based on patient conditions and radiographic findings, as joint erosions or decalcification. However, early signs of arthritis are joint effusion, hypervascularization and synovial hypertrophy. In particular, vascularization has been shown to correlate with arthritis' destructive behavior, more than clinical assessment. Contrast Enhanced Ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. The evaluation of perfusion pattern rely on subjective semiquantitative scales, that are able to capture the macroscopic degree of vascularization, but are unable to detect the subtler differences in kinetics perfusion parameters that might lead to a deeper understanding of disease progression and a better management of patients. We show that after a kinetic analysis of contrast agent appearance, providing the quantitative features characterizing the perfusion pattern of the joint, it is possible to accurately discriminate RA from PSA by building a random forest classifier on the computed features. We compare its accuracy with the assessment performed by expert radiologist blinded of the diagnosis.

Prednisolone phosphate-containing TRX-20 liposomes inhibit cytokine and chemokine production in human fibroblast-like synovial cells: a novel approach to rheumatoid arthritis therapy.

Science.gov (United States)

Harigai, Takashi; Hagiwara, Hitomi; Ogawa, Yumi; Ishizuka, Takanobu; Kaneda, Shinichi; Kimura, Junji

2007-01-01

To evaluate the potential of using prednisolone phosphate (PSLP)-containing 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20) liposomes to treat rheumatoid arthritis (RA), we examined their ability to bind human fibroblast-like synovial (HFLS) cells and their effects in these cells. To test for binding, Lissamine rhodamine B-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (rhodamine)-labelled PSLP-containing TRX-20 liposomes were added to HFLS cells, and the fluorescence intensity of the rhodamine bound to the cells was evaluated. Rhodamine-labelled PSLP-containing liposomes without TRX-20 were used as a negative control. To evaluate the uptake of liposomes by the HFLS cells, we used TRX-20 liposomes containing 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) and p-xylene-bis-pyridinium bromide (DPX), and observed the cells by fluorescence microscopy. The effects of the PSLP in TRX-20 liposomes on HFLS cells were assessed by the inhibition of the production of two inflammatory cytokines (interleukin 6 and granulocyte macrophage colony-stimulating factor) and one inflammatory chemokine (interleukin 8). The interaction of the PSLP-containing TRX-20 liposomes with HFLS cells was approximately 40 times greater than that of PSLP-containing liposomes without TRX-20. PSLP-containing TRX-20 liposomes bound to HFLS cells primarily via chondroitin sulfate. TRX-20 liposomes taken up by the cell were localized to acidic compartments. Furthermore, the PSLP-containing TRX-20 liposomes inhibited the production of the inflammatory cytokines and the chemokine more effectively than did the PSLP-containing liposomes without TRX-20. These results indicate that PSLP-containing TRX-20 liposomes show promise as a novel drug delivery system that could enhance the clinical use of glucocorticoids for treating RA.

Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis

International Nuclear Information System (INIS)

Londei, M.; Savill, C.M.; Verhoef, A.; Brennan, F.; Leech, Z.A.; Feldmann, M.; Duance, V.; Maini, R.N.

1989-01-01

Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis

Magnetic resonance imaging-determined synovial membrane and joint effusion volumes in rheumatoid arthritis and osteoarthritis: comparison with the macroscopic and microscopic appearance of the synovium

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Løvgreen-Nielsen, P

1997-01-01

OBJECTIVE: To evaluate the relationship between synovial membrane and joint effusion volumes determined by magnetic resonance imaging (MRI) and macroscopic and microscopic synovial pathologic findings in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial biopsies...... were performed, and macroscopic grades of synovitis assigned, at preselected knee sites during arthroscopy or arthrotomy in 17 knees with RA and 25 with OA. Synovial inflammation and 9 separate tissue characteristics were graded histologically. Synovial membrane and joint effusion volumes were...... membrane and effusion volumes may be sensitive markers and/or predictors of disease activity and treatment outcome in RA....

Dynamic contrast-enhanced magnetic resonance imaging of articular and extraarticular synovial structures of the hands in patients with psoriatic arthritis

DEFF Research Database (Denmark)

Cimmino, Marco Amedeo; Barbieri, Francesca; Boesen, Mikael

2012-01-01

Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, evaluates synovitis and bone marrow edema in psoriati...... arthritis (PsA). In this pilot study, we looked at possible differences between joint synovitis and tenosynovitis in PsA as compared with rheumatoid arthritis (RA)....

Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis

DEFF Research Database (Denmark)

Østergaard, Mikkel; Hansen, M; Stoltenberg, M

1999-01-01

OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying a......OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease......-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P

Th17 in Animal Models of Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Motomu Hashimoto

2017-07-01

Full Text Available IL-17-secreting helper CD4 T cells (Th17 cells constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.

Changes in synovial membrane and joint effusion volumes after intraarticular methylprednisolone. Quantitative assessment of inflammatory and destructive changes in arthritis by MRI

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Gideon, P

1996-01-01

OBJECTIVE: To evaluate synovial membrane volumes, effusion volumes, and cartilage and bone erosion scores determined by magnetic resonance imaging (MRI) as markers of disease activity and severity in arthritis. METHODS: Gadolinium-DTPA enhanced MRI of 18 arthritic knees was performed before and 1......, 7, 30 and 180 days after intraarticular methylprednisolone injection until clinical relapse. Intraobserver, interobserver, and inter-MRI variations were determined from 2 successive MRI of another 6 knees. RESULTS: In all knees synovial membrane and effusion volumes decreased within the first...... posttreatment week (median decrease 49 and 65%, respectively), and remained low during remission. Synovial volumes, but not effusion volumes, increased to pretreatment levels in case of clinical relapse, indicating that synovial volumes were most important to the clinical appearance. The intraobserver...

The pathogenesis of rheumatoid arthritis in radiological studies. Part I: Formation of inflammatory infiltrates within the synovial membrane

Directory of Open Access Journals (Sweden)

Iwona Sudoł‑Szopińska

2012-06-01

Full Text Available Rheumatoid arthritis is a chronic inflammatory disease with a multifactorial etiology and varied course, which in the majority of patients leads to partial disability or to permanent handicap. Its characteristic trait is a persistent inflammation of the synovial membrane and the formation of an invasive synovial tissue, called the pannus, which in time leads to destruction of the cartilage, subchondral bone tissue, and the soft tissue of the affected joint(s. The pathogenesis of rheumatoid arthritis is complex and involves cells of both innate and adaptive immunity, a network of various cytokines and an immunoregulatory dysfunction. An important role in the discovery of rheumatoid arthritis pathogenesis was played by magnetic resonance imaging, which showed the disease process to extend beyond the synovium into the bone marrow. Many studies have shown a strict correlation between the vascularity of the synovium (assessed through the power Doppler ultrasound and magnetic resonance examinations, bone marrow edema and the clinical, laboratory and histopathological parameters of rheumatoid arthritis. From the current understanding of rheumatoid arthritis, bone erosions could occur from two directions: from the joint cavity and from the bone marrow. With power Doppler ultrasound, as well as in magnetic resonance imaging, it is possible to visualize the well-vascularized pannus and its destructive effects on joint structures and ligaments. In addition, the magnetic resonance study shows inflammatory and destructive changes within the bone marrow (bone marrow edema, inflammatory cysts, and erosions. Bone marrow edema occurs in 68–75% of patients with early rheumatoid arthritis and is considered to be a predictor of rapid disease progression.

Synovial fluid sedimentation in the immobile patient: a commentary on modern septic arthritis and the addition of a new variable confounding diagnosis

Directory of Open Access Journals (Sweden)

Cunningham G

2013-01-01

Full Text Available Gregory Cunningham,1 Brendan Ricciardo21Royal Perth Hospital, Perth, Western Australia, Australia; 2Bunbury Regional Hospital, Bunbury, Western Australia, AustraliaAbstract: Septic arthritis is a serious cause of morbidity and mortality. Despite recent advances, monoarticular and polyarticular septic arthritis (SA have a mortality rate of approximately 11% and 30%, respectively. SA has a 40% risk of permanent loss of joint function. Diagnosis of SA is difficult, given that no rapidly available individual test proves 100% sensitive or 100% specific. There are no previous reports on the phenomenon of synovial fluid sedimentation in an immobile patient, although the occurrence has been identified in vitro. This commentary also presents an extended report of a patient who had been immobile and supine for 24 hours before her right knee was aspirated and treated for septic arthritis. Due to her immobilization, the synovial fluid had settled. The color and opacity of the sequential aliquots from one arthrocentesis was noted to change from light straw-colored, to thick opaque purulent material. Laboratory reports showed increasing white cell counts (WCCs, from 2.6 × 109 to 78 × 109 between the sequential samples. This demonstrates a newly identified phenomenon of sedimentation. This might have led to a diagnostic difficulty, had the knee not been fully aspirated. Aspiration serves as a diagnostic tool, because it collects a sample, but it also serves as a treatment measure, because it removes purulent material. Complete aspiration of the joint should be performed for full therapeutic benefit and to avoid the potential diagnostic confusion of a falsely low WCC due to this newly identified phenomenon of synovial fluid sedimentation in the immobile patient.Keywords: septic arthritis, inflammatory arthritis, joint, sedimentation, orthopedic

Quantitative assessment of the synovial membrane in the rheumatoid wrist: an easily obtained MRI score reflects the synovial volume

DEFF Research Database (Denmark)

Østergaard, Mikkel; Hansen, M; Stoltenberg, M

1996-01-01

Determination of the synovial membrane volume in the rheumatoid arthritis (RA) wrist by gadolinium-DTPA-enhanced MRI is introduced. Moreover, dynamic imaging and an MRI score of synovial hypertrophy, based on gradings in six regions, are evaluated as substitutes of the time-consuming volume...

Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis.

Science.gov (United States)

Tolboom, Tanja C A; van der Helm-Van Mil, Annette H M; Nelissen, Rob G H H; Breedveld, Ferdinand C; Toes, René E M; Huizinga, Tom W J

2005-07-01

Rheumatoid arthritis (RA) is characterized by inflammation and destruction of synovial joints. Fibroblast-like synoviocytes (FLS) harvested from synovial tissue of patients with RA can invade normal human cartilage in severe combined immunodeficient (SCID) mice and Matrigel basement membrane matrix in vitro. This study was undertaken to investigate the association of these in vitro characteristics with disease characteristics in patients with RA. Synovial tissue samples from 72 RA and 49 osteoarthritis (OA) patients were obtained. Samples of different joints were collected from 7 patients with RA. The FLS invasiveness in Matrigel was studied, and the intraindividual and interindividual differences were compared. From the patients with FLS who exhibited the most extreme differences in in vitro ingrowth (most and least invasive FLS), radiographs of the hands and feet were collected and scored according to the Sharp/van der Heijde method to determine the relationship between in vitro invasion data and estimated yearly joint damage progression. FLS from patients with RA were more invasive than FLS from patients with OA (P patient characteristic. The mean +/- SEM Sharp score on radiographs of the hands or feet divided by the disease duration was 4.4 +/- 1.1 units per year of disease duration in patients with the least invasive FLS (n = 9), which was much lower compared with the 21.8 +/- 3.1 units per year of disease duration in patients with the most invasive FLS (n = 9) (P patient characteristic, given the much smaller intraindividual than interindividual FLS variation.

Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis.

Science.gov (United States)

van Lent, P L; Licht, R; Dijkman, H; Holthuysen, A E; Berden, J H; van den Berg, W B

2001-11-01

Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex-mediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of apoptotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.

Cartilage damage and bone erosion are more prominent determinants of functional impairment in longstanding experimental arthritis than synovial inflammation

Directory of Open Access Journals (Sweden)

Silvia Hayer

2016-11-01

Full Text Available Chronic inflammation of articular joints causing bone and cartilage destruction consequently leads to functional impairment or loss of mobility in affected joints from individuals affected by rheumatoid arthritis (RA. Even successful treatment with complete resolution of synovial inflammatory processes does not lead to full reversal of joint functionality, pointing to the crucial contribution of irreversibly damaged structural components, such as bone and cartilage, to restricted joint mobility. In this context, we investigated the impact of the distinct components, including synovial inflammation, bone erosion or cartilage damage, as well as the effect of blocking tumor necrosis factor (TNF on functional impairment in human-TNF transgenic (hTNFtg mice, a chronic inflammatory erosive animal model of RA. We determined CatWalk-assisted gait profiles as objective quantitative measurements of functional impairment. We first determined body-weight-independent gait parameters, including maximum intensity, print length, print width and print area in wild-type mice. We observed early changes in those gait parameters in hTNFtg mice at week 5 – the first clinical signs of arthritis. Moreover, we found further gait changes during chronic disease development, indicating progressive functional impairment in hTNFtg mice. By investigating the association of gait parameters with inflammation-mediated joint pathologies at different time points of the disease course, we found a relationship between gait parameters and the extent of cartilage damage and bone erosions, but not with the extent of synovitis in this chronic model. Next, we observed a significant improvement of functional impairment upon blocking TNF, even at progressed stages of disease. However, blocking TNF did not restore full functionality owing to remaining subclinical inflammation and structural microdamage. In conclusion, CatWalk gait analysis provides a useful tool for quantitative

Involvement of 15-lipoxygenase in the inflammatory arthritis.

Science.gov (United States)

Wu, Ming-Yueh; Lin, Tzu-Hung; Chiu, Yung-Cheng; Liou, Houng-Chi; Yang, Rong-Sen; Fu, Wen-Mei

2012-07-01

15-Lipoxygenase (15-LOX) is involved in many pathological processes. The aim of this study is to examine the role of 15-LOX in the matrix metalloproteinase (MMP) expression and inflammatory arthritis. It was found that treatment of 15-LOX downstream product of 15-(S)-HETE (15-S-hydroxyeicosatetraenoic acid) increased the mRNA and protein levels of MMP-2 in rheumatoid arthritis synovial fibroblast (RASF) derived from rheumatoid arthritis patients. The enhancement effect of 15-(S)-HETE was antagonized by the addition of LY294002 (PI3K inhibitor) and PDTC (NF-κB inhibitor). Treatment of 15-(S)-HETE increased the phosphorylation of AKT, nuclear translocation of p65 and the breakdown of IκBα. TNF-α and IL-1β are the key cytokines involved in arthritis and also increase the activity of MMP-2 in RASF, which was antagonized by pretreatment with 15-LOX inhibitor PD146176 or knockdown of 15-LOX. It was also found that these two cytokines increased the expression of 15-LOX in RASF. Treatment of glucocorticoid but not NSAIDs inhibited 15-(S)-HETE-induced expression of MMP-2. In comparison with wild-type mice, adjuvant-induced arthritis and MMP-2 expression in synovial membrane were markedly inhibited in 15-LOX knockout (KO) mice. These results indicate that 15-LOX plays an important role in the disease progression of arthritis and may be involved in the inflammatory action induced by TNF-α and IL-1β. 15-LOX is thus a good target for developing drugs in the treatment of inflammatory arthritis. Copyright © 2012 Wiley Periodicals, Inc.

[Diagnosis: synovial fluid analysis].

Science.gov (United States)

Gallo Vallejo, Francisco Javier; Giner Ruiz, Vicente

2014-01-01

Synovial fluid analysis in rheumatological diseases allows a more accurate diagnosis in some entities, mainly infectious and microcrystalline arthritis. Examination of synovial fluid in patients with osteoarthritis is useful if a differential diagnosis will be performed with other processes and to distinguish between inflammatory and non-inflammatory forms. Joint aspiration is a diagnostic and sometimes therapeutic procedure that is available to primary care physicians. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Chemopreventive effects of a curcumin-like diarylpentanoid [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] in cellular targets of rheumatoid arthritis in vitro.

Science.gov (United States)

Lee, Ka-Heng; Abas, Faridah; Mohamed Alitheen, Noorjahan Banu; Shaari, Khozirah; Lajis, Nordin Haji; Israf, Daud Ahmad; Syahida, Ahmad

2015-07-01

Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. In this study, BDMC33 (2,6-bis[2,5-dimethoxybenzylidene]cyclohexanone), a curcumin analogue with enhanced anti-inflammatory activity has been synthesized and the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) were evaluated in vitro. Synovial fibroblast cells (HIG-82) were cultured in vitro and induced by phorbol-12-myristate acetate (PMA) to stimulate the expression of matrix metalloproteinase (MMPs) and pro-inflammatory cytokines. The protective effects of BDMC33 were evaluated toward MMP activities, pro-inflammatory cytokine expression and nuclear factor kappa-B (NF-κB) activation by using various bioassay methods, including zymography, Western blotting, reverse transcription polymerase chain reaction, immunofluorescense microscopy and electrophoretic mobility shift assay. The results showed that BDMC33 significantly inhibited the pro-gelatinase B (pro-MMP-9) and collagenase activities via suppression of MMP-1 in activated SF. In addition, BDMC33 strongly suppressed MMP-3 gene expression as well as inhibited COX-2 and IL-6 pro-inflammatory gene expression. We also demonstrated that BDMC33 abolished the p65 NF-κB nuclear translocation and NF-κB DNA binding activity in PMA-stimulated SF. BDMC33 represents an effective chemopreventive agent and could be used as a promising lead compound for further development of rheumatoid arthritis therapeutic intervention. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures

LENUS (Irish Health Repository)

Nic An Ultaigh, Sinead

2011-02-23

Abstract Introduction The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells. Methods RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1\\/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg\\/ml), an anti-TLR2 antibody (OPN301, 1 μg\\/ml) or an immunoglobulin G (IgG) (1 μg\\/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology. Results Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab. Conclusions These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.

Des-Lys58-beta 2m and native beta 2m in rheumatoid arthritis serum and synovial fluid

DEFF Research Database (Denmark)

Williams, R C; Malone, C C; Nissen, Mogens Holst

1995-01-01

-Lys58-beta 2m were found in 80% of 21 SF from RA patients and in 43% of 41 SF from other subjects with various forms of inflammatory arthritis. In RA and other disorders such as gout or pseudogout, levels of Des-Lys58-beta 2m were higher in synovial fluid than in serum during an acute episode...

Scoring of synovial membrane hypertrophy and bone erosions by MR imaging in clinically active and inactive rheumatoid arthritis of the wrist

DEFF Research Database (Denmark)

Østergaard, Mikkel; Gideon, P; Sørensen, K

1995-01-01

MRI-scores of synovial membrane hypertrophy and bone erosions of the RA-wrist are introduced. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) and conventional radiography (CR) of the wrist were performed in 16 patients with rheumatoid arthritis (RA) and 3 healthy controls. A MRI...

C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid

DEFF Research Database (Denmark)

Hornum, Lars; Hansen, Anker Jon; Tornehave, Ditte

2017-01-01

synovial fluid was significantly inhibited by anti-C5aR. The data support that the C5a-C5aR axis may be driving the infiltration of inflammatory cells into the synovial fluid and synovium in both rheumatoid and psoriatic arthritis, and suggest that C5a or C5aR may be a promising treatment target in both...... a Boyden chamber. Appropriate statistical tests were applied for comparisons. C5aR+ cells were detected in most rheumatoid arthritis, in all psoriatic arthritis, but not in non-inflammatory control synovia. C5aR+ cells were primarily neutrophils and macrophages. C5aR+ macrophages were mainly found...

Changes in synovial membrane and joint effusion volumes after intraarticular methylprednisolone. Quantitative assessment of inflammatory and destructive changes in arthritis by MRI

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Gideon, P

1996-01-01

OBJECTIVE: To evaluate synovial membrane volumes, effusion volumes, and cartilage and bone erosion scores determined by magnetic resonance imaging (MRI) as markers of disease activity and severity in arthritis. METHODS: Gadolinium-DTPA enhanced MRI of 18 arthritic knees was performed before and 1...

Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis

International Nuclear Information System (INIS)

Kawahito, Yutaka; Ichinose, Sizuko; Sano, Hajime; Tsubouchi, Yasunori; Kohno, Masataka; Yoshikawa, Toshikazu; Tokunaga, Daisaku; Hojo, Tatsuya; Harasawa, Ryo; Nakano, Teruaki; Matsuda, Kazuhiro

2008-01-01

Mycoplasma fermentans has been suspected as one of the causative pathogenic microorganisms of rheumatoid arthritis (RA) however, the pathogenic mechanism is still unclear. We, previously, reported that glycolipid-antigens (GGPL-I and III) are the major antigens of M. fermentans. Monoclonal antibody against the GGPL-III could detect the existence of the GGPL-III antigens in synovial tissues from RA patients. GGPL-III antigens were detected in 38.1% (32/84) of RA patient's tissues, but not in osteoarthritis (OA) and normal synovial tissues. Immunoelectron microscopy revealed that a part of GGPL-III antigens are located at endoplasmic reticulum. GGPL-III significantly induced TNF-α and IL-6 production from peripheral blood mononulear cells, and also proliferation of synovial fibroblasts. Further study is necessary to prove that M. fermentans is a causative microorganism of RA; however, the new mechanisms of disease pathogenesis provides hope for the development of effective and safe immunotherapeutic strategies based on the lipid-antigen, GGPL-III, in the near future

Contrast-enhanced MRI of the knee in children unaffected by clinical arthritis compared to clinically active juvenile idiopathic arthritis patients

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Nusman, Charlotte M.; Hemke, Robert [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); University of Amsterdam, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children' s Hospital AMC, Amsterdam (Netherlands); Benninga, Marc A.; Kindermann, Angelika [University of Amsterdam, Department of Pediatric Gastroenterology, Emma Children' s Hospital AMC, Amsterdam (Netherlands); Schonenberg-Meinema, Dieneke; Berg, J.M. van den; Kuijpers, Taco W. [University of Amsterdam, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children' s Hospital AMC, Amsterdam (Netherlands); Rossum, Marion A.J. van [University of Amsterdam, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children' s Hospital AMC, Amsterdam (Netherlands); Reade, Department of Pediatric Rheumatology, Amsterdam (Netherlands); Maas, Mario [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands)

2016-04-15

To evaluate enhancing synovial thickness upon contrast-enhanced magnetic resonance imaging (MRI) of the knee in children unaffected by clinical arthritis compared with clinically active juvenile idiopathic arthritis (JIA) patients. A secondary objective was optimization of the scoring method based on maximizing differences on MRI between these groups. Twenty-five children without history of joint complaints nor any clinical signs of joint inflammation were age/sex-matched with 25 clinically active JIA patients with arthritis of at least one knee. Two trained radiologists, blinded for clinical status, independently evaluated location and extent of enhancing synovial thickness with the validated Juvenile Arthritis MRI Scoring system (JAMRIS) on contrast-enhanced axial fat-saturated T1-weighted MRI of the knee. Enhancing synovium (≥2 mm) was present in 13 (52 %) unaffected children. Using the total JAMRIS score for synovial thickening, no significant difference was found between unaffected children and active JIA patients (p = 0.091). Additional weighting of synovial thickening at the JIA-specific locations enabled more sensitive discrimination (p = 0.011). Mild synovial thickening is commonly present in the knee of children unaffected by clinical arthritis. The infrapatellar and cruciate ligament synovial involvement were specific for JIA, which - in a revised JAMRIS - increases the ability to discriminate between JIA and unaffected children. (orig.)

Contrast-enhanced MRI of the knee in children unaffected by clinical arthritis compared to clinically active juvenile idiopathic arthritis patients

International Nuclear Information System (INIS)

Nusman, Charlotte M.; Hemke, Robert; Benninga, Marc A.; Kindermann, Angelika; Schonenberg-Meinema, Dieneke; Berg, J.M. van den; Kuijpers, Taco W.; Rossum, Marion A.J. van; Maas, Mario

2016-01-01

To evaluate enhancing synovial thickness upon contrast-enhanced magnetic resonance imaging (MRI) of the knee in children unaffected by clinical arthritis compared with clinically active juvenile idiopathic arthritis (JIA) patients. A secondary objective was optimization of the scoring method based on maximizing differences on MRI between these groups. Twenty-five children without history of joint complaints nor any clinical signs of joint inflammation were age/sex-matched with 25 clinically active JIA patients with arthritis of at least one knee. Two trained radiologists, blinded for clinical status, independently evaluated location and extent of enhancing synovial thickness with the validated Juvenile Arthritis MRI Scoring system (JAMRIS) on contrast-enhanced axial fat-saturated T1-weighted MRI of the knee. Enhancing synovium (≥2 mm) was present in 13 (52 %) unaffected children. Using the total JAMRIS score for synovial thickening, no significant difference was found between unaffected children and active JIA patients (p = 0.091). Additional weighting of synovial thickening at the JIA-specific locations enabled more sensitive discrimination (p = 0.011). Mild synovial thickening is commonly present in the knee of children unaffected by clinical arthritis. The infrapatellar and cruciate ligament synovial involvement were specific for JIA, which - in a revised JAMRIS - increases the ability to discriminate between JIA and unaffected children. (orig.)

Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts

NARCIS (Netherlands)

García, S.; Bodaño, A.; Pablos, J. L.; Gómez-Reino, J. J.; Conde, C.

2008-01-01

To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Cultured FLS from patients with RA were

Adrenomedullin Regulates IL-1β Gene Expression in F4/80+ Macrophages during Synovial Inflammation

Science.gov (United States)

Takano, Shotaro; Miyagi, Masayuki; Inoue, Gen; Aikawa, Jun; Iwabuchi, Kazuya; Takaso, Masashi

2017-01-01

Adrenomedullin (AM) plays an important role in the regulation of inflammatory processes; however, the role and expression of AM in synovial inflammation have not been determined. To investigate the expression and role of AM in inflamed synovial tissue (ST), the gene expression profiles of AM in the ST, including synovial macrophages and fibroblasts, of a murine patellar surgical dislocation model were characterized. In addition, the effects of interleukin- (IL-) 1β and AM in cultured synovial cells were also examined. CD11c+ macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression of CD11c, IL-1β, AM, receptor activity-modifying proteins 2 (RAMP2), and 3 (RAMP3) was also observed in ST obtained from the dislocated side. AM expression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1β treatment. Synovial macrophages also highly expressed RAMP3 compared to fibroblasts and this expression was further stimulated by exogenously added IL-1β. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibited IL-1β expression. Taken together, these findings demonstrated that AM was produced by synovial fibroblasts and macrophages in inflamed ST and that increased levels of AM may exert anti-inflammatory effects on synovial macrophages. PMID:28299347

MR imaging of abnormal synovial processes

International Nuclear Information System (INIS)

Quinn, S.F.; Sanchez, R.; Murray, W.T.; Silbiger, M.L.; Ogden, J.; Cochran, C.

1987-01-01

MR imaging can directly image abnormal synovium. The authors reviewed over 50 cases with abnormal synovial processes. The abnormalities include Baker cysts, semimembranous bursitis, chronic shoulder bursitis, peroneal tendon ganglion cyst, periarticular abscesses, thickened synovium from rheumatoid and septic arthritis, and synovial hypertrophy secondary to Legg-Calve-Perthes disease. MR imaging has proved invaluable in identifying abnormal synovium, defining the extent and, to a limited degree, characterizing its makeup

Multicenter study of radiosynoviorthesis. Clinical outcome in osteoarthritis and other disorders with concomitant synovitis in comparison with rheumatoid arthritis; Multizenterstudie zur Radiosynoviorthese: Klinische Ergebnisse bei aktivierten Arthrosen und anderen Gelenkerkrankungen mit chronischer Synovialitis im Vergleich zur rheumatoiden Arthritis

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Rau, H.; Lohmann, K.; Spitz, J. [Praxis fuer Nuklearmedizin, am Staedtischen Klinikum Wiesbaden (Germany); Franke, C. [Praxis fuer Nuklearmedizin, Hamburg (Germany); Goretzki, G. [Praxis fuer Nuklearmedizin, Bielefeld (Germany); Lemb, M.A. [Praxis fuer Nuklearmedizin, Bremen (Germany); Mueller, J. [Klinik fuer Nuklearmedizin, Kantonspital St. Gallen (Switzerland); Panholzer, P.J. [Abt. fuer Nuklearmedizin und Endokrinologie, PET-Zentrum, Krankenhaus der Barmherzigen Schwestern, Linz (Austria); Stelling, E. [Praxis fuer diagnostische und therapeutische Nuklearmedizin, Berlin (Germany)

2004-04-01

Aim: evaluation of the effectiveness of radiosynoviorthesis (RSO) in osteoarthritis and other disorders with concomitant synovitis versus rheumatoid arthritis by means of a standardized questionnaire. Patients, methods: 803 RSO treatments were monitored in 691 patients by standardized questionnaires of 7 centers in 3 countries. Patients were assigned to 3 groups according to their age (20-40, 41-60, 61-80 years). Additionally, the data were analyzed separately for patients with rheumatoid arthritis (group A) and those with osteoarthritis, psoriasis arthritis, pigmental villonodular synovitis or persistent effusions after joint replacement (group B). Results: ameliorations of joint pain, swelling/effusion or flexibility were found in 80% of group A and 56% of group B (p <0.01). Quality of life improved in 78% of group A and 59% of group B (p <0.01). The response rate was similar for small- and large-sized joints in group A, but significantly higher for large-sized joints in group B (p <0.01). The positive effects on joint pain, swelling/effusion or flexibility lasted longer in group A (p <0.01). Repeated RSOs were as effective as initial ones. The clinical outcome was neither influenced by age, nor gender, nor transient immobilisation for 48 hours after RSO. Conclusion: although slightly more efficient in rheumatoid arthritis, RSO represents an effective treatment option also in osteoarthritis and other disorders with concomitant synovitis. (orig.) [German] Ziel: Effektivitaetsvergleich der Radiosynoviorthese (RSO) bei aktivierter Arthrose und anderen Gelenkerkrankungen mit chronischer Synovialitis versus rheumatoider Arthritis. Ueberpruefung der Eignung eines standardisierten Fragebogens fuer Multizenterstudien. Patienten, Methoden: Bei 691 Patienten wurden 803 RSO-Behandlungsverlaeufe von 7 Zentren in 3 Laendern mit Hilfe eines standardisierten Fragebogens erfasst. Die Patienten wurden 3 Alterskategorien (20-40, 41-60 und 61-80 Jahre) zugeordnet. Ausserdem wurden

Cryotherapy decreases synovial Doppler activity and pain in knee arthritis: A randomized-controlled trial.

Science.gov (United States)

Guillot, Xavier; Tordi, Nicolas; Prati, Clément; Verhoeven, Frank; Pazart, Lionel; Wendling, Daniel

2017-07-01

To measure and compare the effects of 2 local cryotherapy techniques on synovial power Doppler activity (primary outcome) and pain in non-septic knee arthritis without any concurrent treatment. 30 patients were randomized (ice: 30min, n=15 or cold CO 2 : 2min, n=15 both applied twice at 8h interval). Contralateral non-treated arthritic knees were used as paired controls (n=11 and n=10 respectively). The PDUS semi-quantitative score (0-3) and pain visual analogic scale were evaluated before/after each cold application, 2min, 2h, 24h after the first application. PDUS scores were checked in double-blind by 2 ultrasonographists. The inter-class effect size of local cryotherapy on the power Doppler score remained significant the day after treatment in local cryotherapy-treated compared to contralateral non-treated knees (Global difference: -1 [95% confidence interval: -1.23; -0.77]; ice: -0.73 [-1.06; -0.4]; CO 2 : -0.7 [-1.18; -0.22]). Both techniques significantly and to the same extent reduced the power Doppler score and pain visual analogic scale at all evaluation times and globally throughout the 24 hour-study period. No dropout nor adverse event was reported. In multivariate analysis, the Power Doppler score decrease was associated with pain decrease, while pain decrease was associated with the female sex and ice technique. Local ice and cold CO 2 applied twice equally reduced synovial Power Doppler activity and pain over 24h in knee arthritis. These effects remained significant the day after treatment. ClinicalTrials.gov identifier: NCT02573298. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs.

Science.gov (United States)

Takakubo, Yuya; Oki, Hiroharu; Naganuma, Yasushi; Saski, Kan; Sasaki, Akiko; Tamaki, Yasunobu; Suran, Yang; Konta, Tsuneo; Takagi, Michiaki

2017-01-01

Podoplanin (PDPN) mediates tumor cell migration and invasion, which phenomena might also play a role in severe rheumatoid arthritis (RA). Therefore, the precise cellular distribution of PDPN and it's relationships with inflammation was studied in RA treated with biologic disease-modifying anti-rheumatic drugs (DMARD) or conventional DMARDs (cDMARD). PDPN+ cells were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%- 50%, 1+; 5%-20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO, n=20) or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell grading of inflammation and cell-typing. Inflammatory synovitis score was 1.4 in both BIO and cDMARD, compared to only 0.2 in OA. PDPN+ cells were found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid aggregates (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was expressed in CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells in the lining layer, and in IL- 17+ cells in lymphoid aggregates in RA. PDPN was markedly increased in the immunologically inflamed RA synovitis, which was surgically treated due to BIO- and cDMARD-resistant RA. PDPN may have potential of a new marker of residual arthritis in local joints for inflammation-associated severe RA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints

NARCIS (Netherlands)

Smith, M. D.; Barg, E.; Weedon, H.; Papengelis, V.; Smeets, T.; Tak, P. P.; Kraan, M.; Coleman, M.; Ahern, M. J.

2003-01-01

Background: Synovial biopsies are used to study synovial immunopathology and are increasingly applied for the evaluation of new therapeutic strategies in chronic arthritis. Therefore, it is essential to be informed on the complete spectrum of synovial immunopathology. Objective: To describe the

Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

Science.gov (United States)

Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

1996-08-01

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

ICAM-1 expression on chondrocytes in rheumatoid arthritis: induction by synovial cytokines

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M. E. Davies

1992-01-01

Full Text Available The intercellular adhesion molecule-1 (ICAM-1 was found by immunostaining chondrocytes in cartilage from three patients with rheumatoid arthritis. Expression of ICAM-1 was restricted to chondrocytes in areas of erodedcartilage adjacent to the invading synovial tissue. Toluidine blue staining of these areas demonstrated severe depletion of the cartilage extracellular matrix. In areas of undamaged cartilage there was no ICAM-1 expression. Since ICAM-1 is not constitutively expressed on normal human articular cartilage, but could be induced in vitro by exogenous IL-1α, TNFα and IFNγ or by co-culturing cartilage with inflammatory rheumatoid synovium, we conclude that the induction of ICAM-1 on rheumatoid chondrocytes results from the synergistic action of a variety of cytokines produced by the inflammatory cells of the invading pannus.

JUVENILE RHEUMATOID ARTHRITIS

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I N Sartika

2012-11-01

Full Text Available Juvenile rheumatoid arthritis (JRA is the most common rheumatic condition in children. JRA is defined as persistent arthritis in 1 or more joints for at least 6 weeks, with the onset before age 16 years. The etiology of JRA is unknown. Antigen activated CD4+ T cell stimulate monocytes, macrophages, and synovial fibroblasts to produce the cytokines Interleukin-1 (IL-1, IL-6, and tumor necrosis factor ? (TNF-? and to secrete matrix metalloproteinases, which lead to chronic inflammation due to infiltration of inflammatory cell, angiogenesis, destruction of cartilage and bone with pannus formation. The 3 major subtypes of JRA are based on the symptoms at disease onset and are designated systemic onset, pauciarticular onset, and polyarticular onset. For all patients, the goals of therapy are to decrease chronic joint pain and suppress the inflammatory process. Poor prognostic have been observed in patients with polyarticular onset, rheumatoid factor, persistent morning stiffness, tenosynovitis, involvement of the small joints, rapid appearance of erosions, active late onset childhood, subcutaneous nodules, or antinuclear antibody.

Enhance and Maintain Chondrogenesis of Synovial Fibroblasts by Cartilage Extracellular Matrix Protein Matrilins

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Pei, Ming; Luo, Junming; Chen, Qian

2008-01-01

Summary Objective Cartilage-specific extracellular matrix (ECM) proteins have been proposed to play key roles in modulating cellular phenotypes during chondrogenesis of mesenchymal stem cells. Matrilin (MATN) 1 and 3 are among the most up-regulated ECM proteins during chondrogenesis. The aim of this study was to analyze their roles in chondrogenesis of mesenchymal fibroblasts from synovium. Methods Primary synovial fibroblasts (SFBs) were purified from porcine synovium and incubated in pellet culture for 18 days. Chondrogenesis of SFB was analyzed by histological staining with safranin-O/fast green, and by quantifying glycosaminoglycans with dimethylmethylene blue assay. The mRNA levels of chondrogenic markers including collagen II, aggrecan, and Sox 9 were quantified by real-time RT-PCR, while the protein levels of Col II and matrilins were determined by western blot analysis. Results SFBs underwent chondrogenesis after incubation with TGF-β1 for three days; however, this process was attenuated during the subsequent incubation period. Expression of a MATN1 or 3 cDNA maintained and further enhanced chondrogenesis of SFBs as shown by increased cartilaginous matrix areas, elevated amount of glycosaminoglycans, and stimulated expression of chondrogenic markers. Conclusion Our findings suggest a novel function for MATN1 and 3 to maintain and enhance chondrogenesis of mesenchymal fibroblasts initiated by TGF-β. Our results also support a critical role of cartilage-specific ECM proteins to modulate cellular phenotypes in the microenvironment during chondrogenic differentiation. PMID:18282772

Enhancing and maintaining chondrogenesis of synovial fibroblasts by cartilage extracellular matrix protein matrilins.

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Pei, M; Luo, J; Chen, Q

2008-09-01

Cartilage-specific extracellular matrix (ECM) proteins have been proposed to play key roles in modulating cellular phenotypes during chondrogenesis of mesenchymal stem cells. Matrilin (MATN)1 and MATN3 are among the most up-regulated ECM proteins during chondrogenesis. The aim of this study was to analyze their roles in chondrogenesis of mesenchymal fibroblasts from synovium. Primary synovial fibroblasts (SFBs) were purified from porcine synovium and incubated in pellet culture for 18 days. Chondrogenesis of SFB was analyzed by histological staining with safranin-O/fast green, and by quantifying glycosaminoglycans (GAG) with dimethylmethylene blue assay. The mRNA levels of chondrogenic markers including collagen II, aggrecan, and Sox 9 were quantified by real-time reverse transcription polymerase chain reaction, while the protein levels of Col II and MATNs were determined by western blot analysis. SFBs underwent chondrogenesis after incubation with transforming growth factor-beta1 (TGF-beta1) for 3 days; however, this process was attenuated during the subsequent incubation period. Expression of a Matn1 or Matn3 cDNA maintained and further enhanced chondrogenesis of SFBs as shown by increased cartilaginous matrix areas, elevated amount of GAG, and stimulated expression of chondrogenic markers. Our findings suggest a novel function for MATN1 and MATN3 to maintain and enhance chondrogenesis of mesenchymal fibroblasts initiated by TGF-beta. Our results also support a critical role of cartilage-specific ECM proteins to modulate cellular phenotypes in the microenvironment during chondrogenic differentiation.

Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen

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Damgaard, Dres; Senolt, Ladislav; Nielsen, Michael Friberg

2014-01-01

INTRODUCTION: Members of the peptidylarginine deiminase (PAD) family catalyse the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation...... in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients. METHODS: An enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate...... for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined. RESULTS: Approximately 150 times lower levels of recombinant human PAD2 (rhPAD2...

Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

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Alivernini, Stefano; Tolusso, Barbara; Petricca, Luca; Bui, Laura; Di Sante, Gabriele; Peluso, Giusy; Benvenuto, Roberta; Fedele, Anna Laura; Federico, Franco; Ferraccioli, Gianfranco; Gremese, Elisa

2017-07-01

To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed. PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68 + , CD20 + , CD3 + cells and CD31 + vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68 + , CD20 + , CD3 + , CD31 + cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68 + (p=0.02) and CD3 + cells (p=0.04) as well as CD31 + vessels (p<0.001) than PDUS-negative patients with RA in remission. PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition. Published by the BMJ

Cell-contact-dependent activation of CD4+ T cells by adhesion molecules on synovial fibroblasts.

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Mori, Masato; Hashimoto, Motomu; Matsuo, Takashi; Fujii, Takao; Furu, Moritoshi; Ito, Hiromu; Yoshitomi, Hiroyuki; Hirose, Jun; Ito, Yoshinaga; Akizuki, Shuji; Nakashima, Ran; Imura, Yoshitaka; Yukawa, Naoichiro; Yoshifuji, Hajime; Ohmura, Koichiro; Mimori, Tsuneyo

2017-05-01

To determine how cell-cell contact with synovial fibroblasts (SF) influence on the proliferation and cytokine production of CD4 +  T cells. Naïve CD4 +  T cells were cultured with SF from rheumatoid arthritis patients, stimulated by anti-CD3/28 antibody, and CD4 +  T cell proliferation and IFN-γ/IL-17 production were analyzed. To study the role of adhesion molecules, cell contact was blocked by transwell plate or anti-intracellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1(VCAM-1) antibody. To study the direct role of adhesion molecules for CD4 +  T cells, CD161 +  or CD161 - naïve CD4 +  T cells were stimulated on plastic plates coated by recombinant ICAM-1 or VCAM-1, and the source of IFN-γ/IL-17 were analyzed. SF enhanced naïve CD4 +  T cell proliferation and IFN-γ/IL-17 production in cell-contact and in part ICAM-1-/VCAM-1-dependent manner. Plate-coated ICAM-1 and VCAM-1 enhanced naïve CD4 +  T cell proliferation and IFN-γ production, while VCAM-1 efficiently promoting IL-17 production. CD161 +  naïve T cells upregulating LFA-1 and VLA-4 were the major source of IFN-γ/IL-17 upon interaction with ICAM-1/VCAM-1. CD4 +  T cells rapidly expand and secrete IFN-γ/IL-17 upon cell-contact with SF via adhesion molecules. Interfering with ICAM-1-/VCAM-1 may be beneficial for inhibiting RA synovitis.

IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes

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Wang, Bing; Ma, Zijian; Wang, Miaomiao; Sun, Xiaotong; Tang, Yawei; Li, Ming; Zhang, Yan; Li, Fang; Li, Xia

2017-01-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction. Activation of fibroblast-like synoviocytes (FLS) is a critical step that promotes disease progression. In this study, we aimed to explore the effect of interleukin-34 (IL-34) on RA FLS as a proinflammatory factor and IL-34-stimulated FLS on the production of Th17. We found that serum IL-34 levels were increased compared to those...

Rheumatoid arthritis in the hand. Chapter 9

International Nuclear Information System (INIS)

Weston, W.J.

1979-01-01

Rheumatoid arthritis is primarily a disease of the synovial membrane. To demonstrate synovial changes it is necessary to show adequate detail of the soft tissue. This is best obtained by using industrial film and by hand-processing. The anatomy of the hand and the radiological appearance of rheumatoid arthritis are described. (author)

Synovial haemangioma presenting as monarticular arthritis of the knee.

OpenAIRE

Hawley, W L; Ansell, B M

1981-01-01

Two children with haemangioma of the synovial membrane presenting as swelling of a knee joint are described; in one patient this was associated with epiphyseal overgrowth. This condition should be considered if blood synovial fluid is obtained and clotting studies are normal.

Citrullinated Chemokines in Rheumatoid Arthritis

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2016-12-01

inflammation, thick- ness of the synovial lining layer, and vascularity (16). These observations support the hypothesis that citrulli- nated chemokines may...Gerszten RE, Garcia-Zepeda EA, Lim YC, Yoshida M, Ding HA, Gimbrone MA, et al. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium...arthritis: regulation of its production in synovial cells by interleukin-1 and tumor necrosis factor. Arthritis Rheum 1993;36:762–71. 35. Hatano Y

Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis

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Reynolds, G; Gibbon, J R; Pratt, A G; Wood, M J; Coady, D; Raftery, G; Lorenzi, A R; Gray, A; Filer, A; Buckley, C D; Haniffa, M A; Isaacs, J D; Hilkens, C M U

2016-01-01

Objective A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. Methods Production of GM-CSF by peripheral blood (PB) and synovial fluid (SF) CD4+ T cells was assessed by ELISA and flow cytometry. In vitro CD4+ T-cell polarisation experiments were performed with T-cell activating CD2/CD3/CD28-coated beads in the absence or presence of pro-Th1 or pro-Th17 cytokines. CD1c+ DC and CD16+ macrophage subsets were flow-sorted and analysed morphologically and functionally (T-cell stimulatory/polarising capacity). Results RA-SF CD4+ T cells produced abundant GM-CSF upon stimulation and significantly more than RA-SF mononuclear cells depleted of CD4+ T cells. GM-CSF-producing T cells were significantly increased in RA-SF compared with non-RA inflammatory arthritis SF, active RA PB and healthy donor PB. GM-CSF-producing CD4+ T cells were expanded by Th1-promoting but not Th17-promoting conditions. Following coculture with RA-SF CD4+ T cells, but not healthy donor PB CD4+ T cells, a subpopulation of monocytes differentiated into CD1c+ infDC; a process dependent on GM-CSF. These infDC displayed potent alloproliferative capacity and enhanced GM-CSF, interleukin-17 and interferon-γ production by CD4+ T cells. InfDC with an identical phenotype to in vitro generated cells were significantly enriched in RA-SF compared with non-RA-SF/tissue/PB. Conclusions We demonstrate a therapeutically tractable feedback loop of GM-CSF secreted by RA synovial CD4+ T cells promoting the differentiation of infDC with potent capacity to induce GM-CSF-producing CD4+ T cells. PMID:25923217

Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced inflammation, synovial hyperplasia, and cartilage destruction in rats.

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Wang, Kai; Zhang, Dongmei; Liu, Yan; Wang, Xuan; Zhao, Jiantong; Sun, Tingting; Jin, Tingting; Li, Baoli; Pathak, Janak L

2018-03-14

Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. CIA was developed in Sprague-Dawley (S.D) rats (n = 60, female) and used as a model resembling RA in humans. Rats were treated with a high or moderate dose of Bi-Qi, or methotrexate (MTX). Effects of the treatment on local joint and systemic inflammation, synovial hyperplasia, cartilage destruction, and other main features in the pathogenesis of CIA were analyzed. Inflamed and swollen ankles and joints were observed in arthritic rats, while Bi-Qi or MTX treatment alleviated these symptoms. Only the Bi-Qi moderate dose decreased RA-induced serum levels of tumor necrosis factor-alpha (TNF-α). Both Bi-Qi and MTX reduced the interleukin (IL)-18 serum level. Protein levels of cartilage oligomeric matrix protein and osteopontin in serum, synovium, and cartilage were elevated in arthritic rats, while Bi-Qi alleviated these effects. Synovial hyperplasia, inflammatory cell infiltration in synovium and a high degree of cartilage degradation was observed in RA, and Bi-Qi or MTX alleviated this effect. Bi-Qi at the moderate dose was the most effective in mitigating CIA-related clinical complications. Our findings showed that Bi-Qi alleviates CIA-induced inflammation, synovial hyperplasia, cartilage destruction, and the other main features in the pathogenesis of CIA. This provides fundamental evidence for the anti-arthritic properties of Bi-Qi and corroborates the use of Bi-Qi TCM formula for the treatment of RA.

Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis

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Marta Bianchessi

2016-01-01

Full Text Available Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP cells in equine synovial fluid (SF and to determine the effect of fibroblast growth factor 2 (FGF-2 on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU assays were performed during primary cultures. At first passage, SF-cells were seeded at low density, with or without FGF-2. Following monolayer expansion and serial immunophenotyping, cells were transferred to chondrogenic pellet cultures. Pellets were analyzed for chondrogenic mRNA expression and cartilage matrix secretion. There was a mean of 59.2 CFU/mL of SF. FGF-2 increased the number of population doublings during two monolayer passages and halved the population doubling times. FGF-2 did not alter the immunophenotype of SF-CPs during monolayer expansion, nor did FGF-2 compromise chondrogenesis. Hypertrophic phenotypic markers were not expressed in control or FGF-2 groups. FGF-2 did prevent the development of a “fibroblastic” cell layer around pellet periphery. FGF-2 significantly accelerates in vitro SF-CP expansion, the major hurdle to clinical application of this cell population, without detrimentally affecting subsequent chondrogenic capacity.

Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel.

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Suzuki, Tomoto; Takakubo, Yuya; Oki, Hiroharu; Liu, Xing; Honma, Ryusuke; Naganuma, Yasushi; Goodman, Stuart B; Kaneko, Mika K; Kato, Yukinari; Takagi, Michiaki

2018-02-01

Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.

Clinicopathological correlations of podoplanin (gp38 expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.

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Manuel J Del Rey

Full Text Available Synovial fibroblasts (SF undergo phenotypic changes in rheumatoid arthritis (RA that contribute to inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38 expression by RA SF.Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-α therapy, changes in gp38 expression were determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF migratory and invasive properties, and to SF platelet crosstalk.gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid neogenesis (LN, and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive gp38 expression that was further induced by TNF-α. In RA patients, anti-TNF-α therapy significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet interaction.In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-α therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute to gene expression by SF.

Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis.

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Chen, J R; Takahashi, M; Suzuki, M; Kushida, K; Miyamoto, S; Inoue, T

1998-12-01

Pentosidine is an advanced glycation endproduct formed by glycosylation and oxidation. Our aim was to develop a means to measure pentosidine in synovial fluid (SF), and to compare its concentration in SF in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to investigate the relationship between its concentration in SF and the disease activity of RA. SF was collected from knee joints in 31 patients with RA and 40 with OA, who had hydrarthrosis. One patient with RA and 7 with OA who had the complication of diabetes mellitus or chronic renal failure made up the DM/CRF group, and the remaining patients made up the RA group (n = 30) and the OA group (n = 33). Pentosidine was measured by the direct HPLC method with column switching after hydrolysis of SF. Pentosidine was detected in all SF and was greater in RA (83.9 +/- 46.0 nmol/l, mean +/- SD) than in OA (40.1 +/- 19.6 nmol/l). Three DM/CRF patients undergoing hemodialysis had markedly high pentosidine levels (482.5 +/- 280.8 nmol/l). There was a significant correlation between pentosidine and C-reactive protein (CRP), erythrocyte sedimentation rate, and Lansbury Index (p Patients with RA were divided into high and low activity groups according to the CRP and Lansbury Index. Pentosidine was significantly higher in the high activity group (CRP > or = 2.0 mg/dl and Lansbury Index > or = 50%) than in the low activity group (CRP < 2.0 and/or Lansbury Index < 50) (100.9 +/- 42.8 vs 58.5 +/- 39.6 nmol/; p = 0.0013). Pentosidine in synovial fluid was higher in RA than in OA. Pentosidine levels in SF were related to the disease activity in RA.

Are Bicipital Synovial Cysts in Children with Systemic Juvenile Idiopathic Arthritis still a Significant Clinical Challenge?

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Kyvsgaard, Nini; Herlin, Troels

2015-01-01

-onset painless swelling on the flexor aspect of the proximal upper arm. This type of synovial cyst has been described as a complication to systemic onset JIA (sJIA). Patients usually have active disease when the cysts develop and most cysts resolve with the medical treatment for arthritis. In some cases...... prednisolone between two and eleven months prior (initial dosage 1-1.5 mg/kg, followed by an attempt to taper off the dose). Two of these patients were also in methotrexate (MTX) treatment. None of the patients had received anti-IL1 nor anti-IL-6 biologics. The remaining patient presented with the cyst...

Doppler ultrasound imaging techniques for assessment of synovial inflammation

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Filippucci E

2013-09-01

Full Text Available Emilio Filippucci,1 Fausto Salaffi,1 Marina Carotti,2 Walter Grassi1 1Rheumatology Department, Polytechnic University of the Marche, Ancona, Italy; 2Department of Radiology, Polytechnic University of the Marche, Ancona, Italy Abstract: Ultrasound is an evolving technique, and the rapid progress made in ultrasound technology over the past ten years has dramatically increased its range of applications in rheumatology. One of the most exciting advances is the use of Doppler ultrasound imaging in the assessment of blood flow abnormalities at the synovial tissue level in patients with chronic inflammatory arthritis. This review describes the Doppler techniques available and their main applications in patients with inflammatory arthritis, discusses the evidence supporting their use, and outlines the latest advances in hardware and software. Spectral, color, and power Doppler allow sensitive assessment of vascular abnormalities at the synovial tissue level. Use of contrast agents enhances visualization of the small synovial vessels using color or power Doppler ultrasound and allows for accurate characterization of the rheumatoid pannus. Doppler techniques represent a unique method for assessment of synovial inflammation, showing blood flow characteristics in real time. They are safe, noninvasive, cost-effective, and have high sensitivity in revealing and monitoring synovitis. However, several questions still need to be answered. In the near future, the Doppler techniques described here, together with upcoming hardware and software facilities, will be investigated further and a consensus will be reached on their feasibility and appropriate use in daily rheumatologic practice. Keywords: power and color Doppler techniques, ultrasound, contrast media, synovitis, rheumatoid arthritis

Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression

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Xinjing Luo

2016-01-01

Full Text Available Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA. Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients. In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α.

Cyclophilin A secreted from fibroblast-like synoviocytes is involved in the induction of CD147 expression in macrophages of mice with collagen-induced arthritis

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Nishioku Tsuyoshi

2012-11-01

Full Text Available Abstract Background Cyclophilin A (CypA, a member of the immunophilin family, is a ubiquitously distributed intracellular protein. Recent studies have shown that CypA is secreted by cells in response to inflammatory stimuli. Elevated levels of extracellular CypA and its receptor, CD147 have been detected in the synovium of patients with RA. However, the precise process of interaction between CypA and CD147 in the development of RA remains unclear. This study aimed to investigate CypA secretion from fibroblast-like synoviocytes (FLS isolated from mice with collagen-induced arthritis (CIA and CypA-induced CD147 expression in mouse macrophages. Findings CIA was induced by immunization with type II collagen in mice. The expression and localization of CypA and CD147 was investigated by immunoblotting and immunostaining. Both CypA and CD147 were highly expressed in the joints of CIA mice. CD147 was expressed in the infiltrated macrophages in the synovium of CIA mice. In vitro, spontaneous CypA secretion from FLS was detected and this secretion was increased by stimulation with lipopolysaccharide. CypA markedly increased CD147 levels in macrophages. Conclusions These findings suggest that an interaction in the synovial joints between extracellular CypA and CD147 expressed by macrophages may be involved in the mechanisms underlying the development of arthritis.

Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort.

LENUS (Irish Health Repository)

Bowes, John

2012-08-01

A number of rheumatoid arthritis (RA) susceptibility genes have been identified in recent years. Given the overlap in phenotypic expression of synovial joint inflammation between RA and psoriatic arthritis (PsA), the authors explored whether RA susceptibility genes are also associated with PsA.

The accuracy of MRI-determined synovial membrane and joint effusion volumes in arthritis. A comparison of pre- and post-aspiration volumes

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Østergaard, Mikkel; Stoltenberg, M; Henriksen, O

1995-01-01

Magnetic resonance imaging (MRI) of 18 knees of patients with arthritis was performed before and immediately after arthrocentesis. Pre- and post-aspiration volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal...... T1-weighted MR-images. The difference between MRI-determined and syringe-determined volumes of aspirated joint fluid was 0-7 ml, median 2 ml, corresponding to 0-18%, median 7%, of the pre-aspiration effusion volume. Synovial membrane volumes, determined before and after arthrocentesis varied 0-10 ml......, median 3 ml (0-17%, median 7%). No significant systematic misinterpretation of the borderline between joint fluid and synovium was found. We conclude that effusion volumes and in all probability also synovial membrane volumes, can be determined by MRI with a maximal analytical error of approximately 20...

Express-diagnostics of rheumatoid arthritis and osteoarthrosis

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Zoltan M. Sigal

2017-09-01

Full Text Available Introduction: Diseases of bones and joints have the third greatest impact on the health of the world population. Rheumatoid arthritis and osteoarthritis are uppermost inflammatory diseases of the joints. The aim of the study is the assessment of the ultrasonography and transillumination pulsooptometry of the knee joint as the diagnostic tools for rheumatoid arthritis and osteoarthrosis. Materials and Methods: 2 266 people (29 % – rheumatoid arthritis, 62 % – osteoarthritis, 9 % – healthy, aged 19–75 years took part in the study. The ultrasonography and transillumination pulsooptometry were conducted. Measurements of hemodynamics and optical density were performed using the device and method of Z. M. Sigal (2007. Results. Various indicators were established, for example, the volume of synovial fluid in the suprapatellar bag for rheumatoid arthritis and osteoarthritis. Optical density for rheumatoid arthritis is three times less than for osteoarthritis. There are significant differences in the amplitude of pulse oscillations in rheumatoid arthritis and osteoarthritis. Results: Various indicators were established, for example, the volume of synovial fluid in the suprapatellar bag for rheumatoid arthritis and osteoarthritis. Optical density for rheumatoid arthritis is three times less than for osteoarthritis. There are significant differences in the amplitude of pulse oscillations in rheumatoid arthritis and osteoarthritis. Discussion and Conclusions: The volume of synovial fluid in the suprapatellar bag of the knee joint with rheumatoid arthritis is higher than in osteoarthritis and normal: 55.8 cm3 and above and 3,29 cm3, 1,85 cm3 and below, respectively. With osteoarthritis and normal amount of synovial fluid did not differ significantly. The optical density in the suprapatellar bag of the knee joint for rheumatoid arthritis was 0.56 ± 0.2, the amplitude of pulse oscillations was 13.45 ± 3.62 mm. In osteoarthritis, these values were 1

Characterization of the porcine synovial fluid proteome and a comparison to the plasma proteome

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Tue Bjerg Bennike

2015-12-01

In addition, we analyzed the proteome of human plasma, and compared the proteomes to the obtained porcine synovial fluid proteome. The proteome of the two body fluids were found highly similar, underlining the detected plasma derived nature of many synovial fluid components. The healthy porcine synovial fluid proteomics data, human rheumatoid arthritis synovial fluid proteomics data used in the method optimization, human plasma proteomics data, and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD000935.

Ultrasound guided synovial biopsy of the wrist

NARCIS (Netherlands)

van Vugt, R. M.; van Dalen, A.; Bijlsma, J. W.

1997-01-01

Seven patients (4 female and 3 male, mean age 46) with arthritis of the wrist (n = 7) without known etiology were evaluated. High-definition ultrasound equipment was used for localization of synovial hypertrophy, suitable for ultrasound guided biopsy without risk. A 18-gauge diameter Tru-cut biopsy

Megakaryocytes compensate for Kit insufficiency in murine arthritis.

Science.gov (United States)

Cunin, Pierre; Penke, Loka R; Thon, Jonathan N; Monach, Paul A; Jones, Tatiana; Chang, Margaret H; Chen, Mary M; Melki, Imene; Lacroix, Steve; Iwakura, Yoichiro; Ware, Jerry; Gurish, Michael F; Italiano, Joseph E; Boilard, Eric; Nigrovic, Peter A

2017-05-01

The growth factor receptor Kit is involved in hematopoietic and nonhematopoietic development. Mice bearing Kit defects lack mast cells; however, strains bearing different Kit alleles exhibit diverse phenotypes. Herein, we investigated factors underlying differential sensitivity to IgG-mediated arthritis in 2 mast cell-deficient murine lines: KitWsh/Wsh, which develops robust arthritis, and KitW/Wv, which does not. Reciprocal bone marrow transplantation between KitW/Wv and KitWsh/Wsh mice revealed that arthritis resistance reflects a hematopoietic defect in addition to mast cell deficiency. In KitW/Wv mice, restoration of susceptibility to IgG-mediated arthritis was neutrophil independent but required IL-1 and the platelet/megakaryocyte markers NF-E2 and glycoprotein VI. In KitW/Wv mice, platelets were present in numbers similar to those in WT animals and functionally intact, and transfer of WT platelets did not restore arthritis susceptibility. These data implicated a platelet-independent role for the megakaryocyte, a Kit-dependent lineage that is selectively deficient in KitW/Wv mice. Megakaryocytes secreted IL-1 directly and as a component of circulating microparticles, which activated synovial fibroblasts in an IL-1-dependent manner. Transfer of WT but not IL-1-deficient megakaryocytes restored arthritis susceptibility to KitW/Wv mice. These findings identify functional redundancy among Kit-dependent hematopoietic lineages and establish an unanticipated capacity of megakaryocytes to mediate IL-1-driven systemic inflammatory disease.

MR imaging of transient synovitis: differentiation from septic arthritis

International Nuclear Information System (INIS)

Yang, W.J.; Im, S.A.; Lim, G.Y.; Chun, H.J.; Jung, N.Y.; Sung, M.S.; Choi, B.G.

2006-01-01

Transient synovitis is the most common cause of acute hip pain in children. However, MR imaging findings in transient synovitis and the role of MR imaging in differentiating transient synovitis from septic arthritis have not been fully reported. To describe the MR findings of transient synovitis and to determine whether the MR characteristics can differentiate this disease entity from septic arthritis. Clinical findings and MR images of 49 patients with transient synovitis (male/female 36/13, mean age 6.1 years) and 18 patients with septic arthritis (male/female 10/8, mean age 4.9 years) were retrospectively reviewed. MR findings of transient synovitis were symptomatic joint effusion, synovial enhancement, contralateral joint effusion, synovial thickening, and signal intensity (SI) alterations and enhancement in surrounding soft tissue. Among these, SI alterations and enhancement in bone marrow and soft tissue, contralateral joint effusion, and synovial thickening were statistically significant MR findings in differentiating transient synovitis from septic arthritis. The statistically significant MR findings in transient synovitis are contralateral (asymptomatic) joint effusions and the absence of SI abnormalities of the bone marrow. It is less common to have SI alterations and contrast enhancement of the soft tissues. The statistically significant MR findings in septic arthritis are SI alterations of the bone marrow, and SI alterations and contrast enhancement of the soft tissue. Ipsilateral effusion and synovial thickening and enhancement are present in both diseases

Oleanolic acid acetate inhibits rheumatoid arthritis by modulating T cell immune responses and matrix-degrading enzymes

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Choi, Jin Kyeong [Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Kim, Sung-Wan; Kim, Duk-Sil [Department of Thoracic and Cardiovascular Surgery, CHA Gumi Medical Center, CHA University, Gumi 730-040 (Korea, Republic of); Lee, Jong Yeong [Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Lee, Soyoung [Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185 (Korea, Republic of); Oh, Hyun-Mee [Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185 (Korea, Republic of); Ha, Yeong Su; Yoo, Jeongsoo [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Park, Pil-Hoon [College of Pharmacy, Yeungnam University, Gyeongbuk 712-749 (Korea, Republic of); Shin, Tae-Yong [College of Pharmacy, Woosuk University, Jeonju 565-701 (Korea, Republic of); Kwon, Taeg Kyu [Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701 (Korea, Republic of); Rho, Mun-Chual, E-mail: rho-m@kribb.re.kr [Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185 (Korea, Republic of); Kim, Sang-Hyun, E-mail: shkim72@knu.ac.kr [Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

2016-01-01

ABSTRACT: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a combination of synovium joint inflammation, synovium hyperplasia, and destruction of cartilage and bone. Oleanolic acid acetate (OAA), a compound isolated from Vigna angularis, has been known to possess pharmacological activities, including anti-inflammation and anti-bone destruction. In this study, we investigated the effects of OAA on RA and the underlying mechanisms of action by using a type-II collagen-induced arthritis (CIA) mouse model and tumor necrosis factor (TNF)-α-stimulated RA synovial fibroblasts. Oral administration of OAA decreased the clinical arthritis symptoms, paw thickness, histologic and radiologic changes, and serum total and anti-type II collagen IgG, IgG1, and IgG2a levels. OAA administration reduced Th1/Th17 phenotype CD4{sup +} T lymphocyte expansions and inflammatory cytokine productions in T cell activated draining lymph nodes and spleen. OAA reduced the expression and production of inflammatory mediators, such as cytokines and matrix metalloproteinase (MMP)-1/3, in the ankle joint tissue and RA synovial fibroblasts by down-regulating Akt, mitogen-activated protein kinases, and nuclear factor-κB. Our results clearly support that OAA plays a therapeutic role in RA pathogenesis by modulating helper T cell immune responses and matrix-degrading enzymes. The immunosuppressive effects of OAA were comparable to dexamethasone and ketoprofen. We provide evidences that OAA could be a potential therapeutic candidate for RA. - Highlights: • OAA attenuated chronic CIA symptoms. • OAA had a regulating effect on the T helper cell immune reaction for CIA. • The effect of OAA on the RA was comparable to the dexamethasone or ketoprofen. • OAA might be a candidate for the treatment of arthritic diseases.

Effect of intraarticular osmic acid on synovial membrane volume and inflammation, determined by magnetic resonance imaging

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Gideon, P

1995-01-01

The changes in MR-determined synovial membrane volume, early synovial enhancement, and cartilage and bone erosions after osmic acid knee synovectomy were studied. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) of 18 knees with persistent arthritis was performed before and 1 month after...

Value of contrast-enhanced ultrasound in rheumatoid arthritis

International Nuclear Information System (INIS)

Zordo, Tobias de; Mlekusch, Sabine P.; Feuchtner, Gudrun M.; Mur, Erich; Schirmer, Michael; Klauser, Andrea S.

2007-01-01

The purpose of this review is to describe the spectrum of sonographic findings in rheumatic diseases with respect to the diagnostic potential using US contrast media which prove activity or inactivity in synovial tissue where new treatment regimes target. Synovial activity can be found in non-erosive and erosive forms of primary and secondary osteoarthritis, and in inflammatory forms of joint diseases like rheumatoid arthritis and peripheral manifestations of spondyloarthritis including, ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis and enteropathic arthritis. It can also be present in metabolic and endocrine forms of arthritis, in connective tissue arthropathies like systemic lupus erythematosus or scleroderma and in infectious arthritis. Ultrasound should be used as first-line imaging modality in suspected early cases of RA and other forms of arthritis, whereas contrast-enhanced ultrasound (CEUS) can further enable for sensitive assessment of vascularity which correlates with disease activity

Value of contrast-enhanced ultrasound in rheumatoid arthritis

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Zordo, Tobias de; Mlekusch, Sabine P.; Feuchtner, Gudrun M. [Department of Radiology II, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck (Austria); Mur, Erich [Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck (Austria); Schirmer, Michael [Department of Internal Medicine, Hospital of the Elisabethines Klagenfurt, Voelkermarkter Strasse 15-19, 9020 Klagenfurt (Austria); Klauser, Andrea S. [Department of Radiology II, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck (Austria)], E-mail: andrea.klauser@i-med.ac.at

2007-11-15

The purpose of this review is to describe the spectrum of sonographic findings in rheumatic diseases with respect to the diagnostic potential using US contrast media which prove activity or inactivity in synovial tissue where new treatment regimes target. Synovial activity can be found in non-erosive and erosive forms of primary and secondary osteoarthritis, and in inflammatory forms of joint diseases like rheumatoid arthritis and peripheral manifestations of spondyloarthritis including, ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis and enteropathic arthritis. It can also be present in metabolic and endocrine forms of arthritis, in connective tissue arthropathies like systemic lupus erythematosus or scleroderma and in infectious arthritis. Ultrasound should be used as first-line imaging modality in suspected early cases of RA and other forms of arthritis, whereas contrast-enhanced ultrasound (CEUS) can further enable for sensitive assessment of vascularity which correlates with disease activity.

Inhibitory Effect of Curcumol on Jak2-STAT Signal Pathway Molecules of Fibroblast-Like Synoviocytes in Patients with Rheumatoid Arthritis

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Heng Wang

2012-01-01

Full Text Available Hyperplasia of synovial membrane in rheumatoid arthritis (RA is a critical pathological foundation for inducing articular injury. The janus kinase and signal transducer and activator of transcription (Jak-STAT pathway plays a critical role in synovial membrane proliferation induced by platelet-derived growth factor (PDGF. To explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome, the changes of Jak2-STAT1/3 signal pathway-related molecules in synoviocytes were observed in vitro. In this study, the fibroblast-like synoviocytes (FLS in patients with RA were collected and cultured. The following parameters were measured: cell proliferation (WST-1 assay, cell cycles (fluorescence-activated cell sorting, FACS, STAT1 and STAT3 activities (electrophoretic mobility shift assay, EMSA, and the protein expressions of phosphorylated Jak2, STAT1, and STAT3 (Western blot. It was shown that curcumol could inhibit the RA-FLS proliferation and DNA synthesis induced by PDGF-BB in a dose-dependent manner in vitro. The transcription factors activities of STAT1 and STAT3 were obviously elevated after PDGF-BB stimulation (P<0.05. Super-shift experiments identified the STAT1 or STAT3 proteins in the complex. Furthermore, the different concentration curcumol could downregulate the DNA binding activities of STAT1 and STAT3 (P<0.05 and inhibit the phosphorylation of Jak2 while it had no effect on the protein expressions of STAT1 and STAT3. Positive correlations were found between changes of cell proliferation and DNA-binding activities of STAT1 and STAT3, respectively (P<0.01. In conclusion, curcumol might suppress the FLS proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2 phosphorylation, downregulating STAT1 and STAT3 DNA-binding activities, which could provide theoretical foundation for clinical treatment of RA.

Tendon synovial cells secrete fibronectin in vivo and in vitro

International Nuclear Information System (INIS)

Banes, A.J.; Link, G.W.; Bevin, A.G.; Peterson, H.D.; Gillespie, Y.; Bynum, D.; Watts, S.; Dahners, L.

1988-01-01

The chemistry and cell biology of the tendon have been largely overlooked due to the emphasis on collagen, the principle structural component of the tendon. The tendon must not only transmit the force of muscle contraction to bone to effect movement, but it must also glide simultaneously over extratendonous tissues. Fibronectin is classified as a cell attachment molecule that induces cell spreading and adhesion to substratum. The external surface of intact avian flexor tendon stained positively with antibody to cellular fibronectin. However, if the surface synovial cells were first removed with collagenase, no positive reaction with antifibronectin antibody was detected. Analysis of immunologically stained frozen sections of tendon also revealed fibronectin at the tendon synovium, but little was associated with cells internal in tendon. The staining pattern with isolated, cultured synovial cells and fibroblasts from the tendon interior substantiated the histological observations. Analysis of polyacrylamide gel profiles of 35 S-methionine-labeled proteins synthesized by synovial cells and internal fibroblasts indicated that fibronectin was synthesized principally by synovial cells. Fibronectin at the tendon surface may play a role in cell attachment to prevent cell removal by the friction of gliding. Alternatively, fibronectin, with its binding sites for hyaluronic acid and collagen, may act as a complex for boundary lubrication

Intraarticular volume and clearance in human synovial effusions

International Nuclear Information System (INIS)

Wallis, W.J.; Simkin, P.A.; Nelp, W.B.; Foster, D.M.

1985-01-01

Intraarticular volumes were measured by radiolabeled albumin (RISA) distribution in chronic knee effusions from 11 rheumatoid arthritis patients and 9 osteoarthritis patients. Volumes of synovial fluid obtained at joint aspiration were substantially less than those found by RISA dilution. Up to 24 hours was needed for full distribution of RISA throughout the intraarticular compartment. Measured 123I and RISA radioactivity over the knee described monoexponential rate constants, lambda (minute-1). The clearance of 123I and RISA from synovial effusions was derived by the formulation volume (ml) X lambda (minute-1) = clearance (ml/minute). RISA clearance in rheumatoid effusions was significantly greater than that found in osteoarthritis effusions. Intraarticular volume and isotope clearance were easily quantified and provide measures for further evaluating the microvascular physiology of synovial effusions

Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli.

Science.gov (United States)

Alsaleh, Ghada; Nehmar, Ramzi; Blüml, Stephan; Schleiss, Cédric; Ostermann, Eleonore; Dillenseger, Jean-Philippe; Sayeh, Amira; Choquet, Philippe; Dembele, Doulaye; Francois, Antoine; Salmon, Jean-Hugues; Paul, Nicodème; Schabbauer, Gernot; Bierry, Guillaume; Meyer, Alain; Gottenberg, Jacques-Eric; Haas, Gabrielle; Pfeffer, Sebastien; Vallat, Laurent; Sibilia, Jean; Bahram, Seiamak; Georgel, Philippe

2016-08-01

While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ). The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay. We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli. The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses. © 2016, American College of Rheumatology.

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways.

Science.gov (United States)

Walsh, Alice M; Wechalekar, Mihir D; Guo, Yanxia; Yin, Xuefeng; Weedon, Helen; Proudman, Susanna M; Smith, Malcolm D; Nagpal, Sunil

2017-01-01

This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission.

β1-Integrin Expression in the Rheumatoid Synovial-Pannus Formation

OpenAIRE

Ishikawa, Hitoshi; Hirata, Soichiro; Isobe, Takashi; Nishibayashi, Yasurou; Kubo, Hitoshi; Nannbae, Masahiro; Nakagawa, Natsuko; Andoh, Yoshihiro

1994-01-01

In order to investigate the mechanism of synovial pannus formation in rheumatoid arthritis, using an immunohistochemical staining technique with monoclonal antibodies against adhesion molecules, anti-CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), CDw49d (VLA-4) and CDw49e (VLA-5), the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction has been investigated. Twelve samples of rheumatoid articular cartilage covered with pannus were examined. Treatment with...

Mechanisms involved in the therapeutic effects of Paeonia lactiflora Pallas in rheumatoid arthritis.

Science.gov (United States)

Zhang, Wei; Dai, Sheng-Ming

2012-09-01

Paeonia lactiflora Pallas, also named Chinese Paeony, is a Chinese herb. A decoction of its root has been used to treat painful or inflammatory disorders in traditional Chinese medicine. A water/ethanol extract of Radix Paeoniae is known as total glycosides of paeony (TGP), of which paeoniflorin is the major active component. Preclinical studies show that TGP/paeoniflorin is able to diminish pain, joint swelling, synovial hypertrophy, and the severity of bone erosion and cartilage degradation in experimental arthritis. TGP/paeoniflorin suppresses inflammatory process by reducing the production of prostaglandin E2, leukotriene B4, nitric oxide, reactive oxygen species, proinflammatory cytokines and chemokines. TGP/paeoniflorin also inhibits the proliferation of lymphocytes and fibroblast-like synoviocytes, the formation of new blood vessels, and the production of matrix metalloproteinases. Clinical data show that TGP is effective to relieve the symptoms and signs of rheumatoid arthritis without significant adverse effects. Recently, TGP is widely used to treat rheumatoid arthritis in China. Copyright © 2012 Elsevier B.V. All rights reserved.

Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

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Joong Kyong Ahn

Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3, which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin. Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA.

Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

Science.gov (United States)

Ahn, Joong Kyong; Kim, Sooah; Hwang, Jiwon; Kim, Jungyeon; Lee, You Sun; Koh, Eun-Mi; Kim, Kyoung Heon; Cha, Hoon-Suk

2015-01-01

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin). Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA.

Extracts of Bauhinia championii (Benth.) Benth. inhibit NF-B-signaling in a rat model of collagen-induced arthritis and primary synovial cells.

Science.gov (United States)

Xu, Wei; Huang, Mingqing; Zhang, Yuqin; Li, Huang; Zheng, Haiyin; Yu, Lishuang; Chu, Kedan

2016-06-05

Bauhinia championii (Benth.) Benth. is used in Chinese traditional medicine to treat arthritis, especially has been used a long time ago on rheumatoid arthritis (RA) in She ethnic minority group. To investigate the anti-RA effect of Bauhinia championii (Benth.) Benth ethyl acetate extract (BCBEE) and the molecular bases of it. BCBEE was studied on a rat model of RA induced by Ⅱcollagen in vivo, as well as on primary synovial cells in vitro. After BCBEE treatment, in vivo, it was showed that paw and joint edema was inhibited, pathological joint changes was ameliorated and the levels of interleukin (IL)-1β and tumor necrosis factor-(TNF-α) was decreased significantly. The protein and mRNA expressions of nuclear factor-B (NF-κB)(p65), IκB, p-IκB and IκB kinase beta (IκKβ) were also down-regulated. Moreover, the in vitro study revealed that BCBEE treatment inhibited primary synovial cells proliferation, and promoted down-regulation of NF-κB(p65), IκB, p-IκB and IκKβ. Taken together, the present study demonstrates that BCBEE produces a protection in a rat model of RA induced by Ⅱcollagen via inhibiting paw and joint edema, ameliorating pathological joint changes and regulating the levels of cytokines and its action mechanism maybe is via down-regulating NF-κB(p65), IκB, p-IκB and IκKβ expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells

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Hai-Shu Lin

2013-11-01

Full Text Available MS-275 (entinostat and SAHA (vorinostat, two histone deacetylase (HDAC inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA. To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α  MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1, an endogenous suppressor of p38α  in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation of p38α  was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2, monocyte chemotactic protein-2 (MCP-2 and macrophage migration inhibitory factor (MIF in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors.

Synovial cyst of the hip joint as a rare cause of unlateral leg edema; A case report

Energy Technology Data Exchange (ETDEWEB)

Kang, Ji Hun; Chang, Il Soo; Park, Sang Woo; Yun, Ik Jin; Park, Hyung Kyu; Kim, Wan Seop; Lee, Hui Jin; Kim, Na Ra; Moon, Sung Gyu [Konkuk University School of Medicine, Seoul (Korea, Republic of)

2015-06-15

A synovial cyst of the hip joint is a rare cause of unilateral leg edema, and it is usually associated with arthropathies such as rheumatoid arthritis and osteoarthritis. An asymptomatic synovial cyst of the hip joint that is not associated with an arthritic condition occurs infrequently. In this paper, we described the case of a 52-year-old woman who presented with unilateral right leg edema caused by a synovial cyst of the hip joint.

False-Negative Rate of Gram-Stain Microscopy for Diagnosis of Septic Arthritis: Suggestions for Improvement

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Paul Stirling

2014-01-01

Full Text Available We quantify the false-negative diagnostic rate of septic arthritis using Gram-stain microscopy of synovial fluid and compare this to values reported in the peer-reviewed literature. We propose a method of improving the diagnostic value of Gram-stain microscopy using Lithium Heparin containers that prevent synovial fluid coagulation. Retrospective study of the Manchester Royal Infirmary microbiology database of patients undergoing synovial fluid Gram-stain and culture between December 2003 and March 2012 was undertaken. The initial cohort of 1896 synovial fluid analyses for suspected septic arthritis was reduced to 143 after exclusion criteria were applied. Analysis of our Gram-stain microscopy yielded 111 false-negative results from a cohort size of 143 positive synovial fluid cultures, giving a false-negative rate of 78%. We report a false-negative rate of Gram-stain microscopy for septic arthritis of 78%. Clinicians should therefore avoid the investigation until a statistically significant data set confirms its efficacy. The investigation's value could be improved by using Lithium Heparin containers to collect homogenous synovial fluid samples. Ongoing research aims to establish how much this could reduce the false-negative rate.

MR imaging findings of acute gouty arthritis

International Nuclear Information System (INIS)

Lee, Gyung Kyu; Lee, Jee Young; Suh, Jin Suck

2006-01-01

The purpose of this study was to describe the clinical and MR imaging features of acute gouty arthritis and to define the characteristic findings that would be helpful for differentiating acute gouty arthritis from septic arthritis. The authors retrospectively studied seven patients who suffered from acute gouty arthritis. The MR imaging findings were analyzed by two musculoskeletal radiologists who focused on joint effusion, subchondral bone erosion, bone marrow edema, synovial thickening (regular and even, or irregular and nodular), and the soft tissue changes (edema or abscess). The clinical records of the patients were reviewed with regard to age and gender, the clinical presentation and the laboratory findings (serum uric acid, WBC, erythrocyte sedimentation rate, C-reactive protein and synovial fluid culture). The patients consisted of six men and one woman whose mean age was 41 years (age range:24-65 years). The joints involved were the knee (n=6), and ankle (n=1). Two patients had medical histories of gouty attacks that involved the first metatarsophalangeal joint. In six cases, the serum uric acid level during acute attacks was elevated. In all the patients, the affected joint became swollen, hot, erythematous and extremely tender, and this was accompanied by a high ESR and a high C-reactive protein level at the time of presentation. The results of Gram stain and culture of the synovial fluid were negative. In all patients, the MR images showed large amounts of joint effusion, thick irregular and nodular synovial thickening and soft tissue edema without subchondral bone erosions and soft tissue abscess. In one case, subchondral bone marrow edema of the medial femoral condyle was present. In five cases, there were multiple low signal foci in the joint on the spin-echo T2-weighted MR image. Even though the MR imaging findings of acute gouty arthritis are nonspecific, it should be considered as a possible diagnosis when a large amount of joint effusion

Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus.

Science.gov (United States)

Shekhani, Mohammed Talha; Forde, Toni S; Adilbayeva, Altynai; Ramez, Mohamed; Myngbay, Askhat; Bexeitov, Yergali; Lindner, Volkhard; Adarichev, Vyacheslav A

2016-07-19

The formation of destructive hypercellular pannus is critical to joint damage in rheumatoid arthritis (RA). The collagen triple helix repeat containing 1 (CTHRC1) protein expressed by activated stromal cells of diverse origin has previously been implicated in tissue remodeling and carcinogenesis. We recently discovered that the synovial Cthrc1 mRNA directly correlates with arthritis severity in mice. This study characterizes the role of CTHRC1 in arthritic pannus formation. Synovial joints of mice with collagen antibody-induced arthritis (CAIA) and human RA-fibroblast-like synoviocytes (FLS) were immunostained for CTHRC1, FLS and macrophage-specific markers. CTHRC1 levels in plasma from patients with RA were measured using sandwich ELISA. The migratory response of fibroblasts was studied with a transwell migration assay and time-lapse microscopy. Velocity and directness of cell migration was analyzed by recording the trajectories of cells treated with rhCTHRC1. Immunohistochemical analysis of normal and inflamed synovium revealed highly inducible expression of CTHRC1 in arthritis (10.9-fold). At the tissue level, CTHRC1-expressing cells occupied the same niche as large fibroblast-like cells positive for α-smooth muscle actin (α-SMA) and cadherin 11 (CDH11). CTHRC1 was produced by activated FLS predominantly located at the synovial intimal lining and at the bone-pannus interface. Cultured RA-FLS expressed CDH11, α-SMA, and CTHRC1. Upon treatment with exogenous rhCTHRC1, embryonic fibroblasts and RA-FLS significantly increased migration velocity, directness, and cell length along the front-tail axis (1.4-fold, p pannus.

Value of CT scan in synovial diseases

Energy Technology Data Exchange (ETDEWEB)

Tamisier, J.N.; Regent, D.; Thomas, P.; Pere, P.; Gaucher, A.; Capesius, P.

1986-02-01

The authors have developed a technique of CT arthroscan which, by the use of a gas or opaque contrast medium, is able to demonstrate the synovial structures of the knee, the shoulder and the hip. Among the essential indications, they include the demonstration of neoplasia of the synovium and the evaluation of the pannus in rheumatoid arthritis. Their secondary indications include the demonstration of fluid effusions in the hip, the precise evaluation of hyperostotic lesions in the same joint, the detection of ossification phenomena in the capsule of the inter-apophyseal joints in ankylosing spondylitis and, in some cases, following negative or doubtful arthrography for the detection of synovial plica. They also recall the usefulness or the arthroscan in the diagnosis of lesions of the labrum glenoidale.

Effect of Sodium Alginate Addition to Resveratrol on Acute Gouty Arthritis

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Peng Wang

2015-04-01

Full Text Available Objective: Resveratrol has been shown to exert anti-inflammatory and antioxidant effects, while sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory properties. We performed an animal study to investigate the effect of sodium alginate addition to resveratrol on acute gouty arthritis. Methods: Twenty-four SPF Wistar mice were randomized to four groups receiving the combination of sodium alginate and resveratrol, resveratrol alone, colchicine, and placebo, respectively. Acute gouty arthritis was induced by injection of 0.05 ml monosodium urate (MSU solution (25g/mL into ankle joint cavity. IL-1β, CCR5, and CXCL10 levels in both serum and synovial fluid were measured using ELISA. NLRP3 expression in the synovial tissues was measured using western plot. Results: The combination of sodium alginate and resveratrol significantly reduced synovial levels of IL-1β, CCR5, and CXCL10 when compared with colchicines, and all P values were less than 0.0001. The combination of sodium alginate and resveratrol was also superior to resveratrol in terms of both serum levels and synovial levels of IL-1β, CCR5, and CXCL10. In addition, resveratrol, with or without sodium alginate, could reduce NLRP3 expression obviously in the synovial tissues. Conclusion: The combination of sodium alginate and resveratrol has better effect over colchicines in treating MSU-induced acute gouty arthritis.

Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

Science.gov (United States)

Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

A systems approach to rheumatoid arthritis.

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Sungyong You

Full Text Available Rheumatoid arthritis (RA is a chronic autoimmune disease that primarily attacks synovial joints. Despite the advances in diagnosis and treatment of RA, novel molecular targets are still needed to improve the accuracy of diagnosis and the therapeutic outcomes. Here, we present a systems approach that can effectively 1 identify core RA-associated genes (RAGs, 2 reconstruct RA-perturbed networks, and 3 select potential targets for diagnosis and treatments of RA. By integrating multiple gene expression datasets previously reported, we first identified 983 core RAGs that show RA dominant differential expression, compared to osteoarthritis (OA, in the multiple datasets. Using the core RAGs, we then reconstructed RA-perturbed networks that delineate key RA associated cellular processes and transcriptional regulation. The networks revealed that synovial fibroblasts play major roles in defining RA-perturbed processes, anti-TNF-α therapy restored many RA-perturbed processes, and 19 transcription factors (TFs have major contribution to deregulation of the core RAGs in the RA-perturbed networks. Finally, we selected a list of potential molecular targets that can act as metrics or modulators of the RA-perturbed networks. Therefore, these network models identify a panel of potential targets that will serve as an important resource for the discovery of therapeutic targets and diagnostic markers, as well as providing novel insights into RA pathogenesis.

Macrophages in synovial inflammation

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Aisling eKennedy

2011-10-01

Full Text Available AbstractSynovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage-pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA. There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished.Here we will briefly review our current understanding of macrophages and macrophage polarisation in RA as well as the elements implicated in controlling polarisation, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype and may represent a novel therapeutic paradigm.

AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis

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Bonnet, Cleo S; Williams, Anwen S; Gilbert, Sophie J; Harvey, Ann K; Evans, Bronwen A; Mason, Deborah J

2015-01-01

Objectives Synovial fluid glutamate concentrations increase in arthritis. Activation of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6 (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA and KA GluRs are expressed in human arthritis, and that intra-articular NBQX (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced arthritis (AIA). Methods GluR immunohistochemistry was related to synovial inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). A single intra-articular NBQX injection was given at induction, and knee swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging, RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human primary osteoblast (HOB) activity were determined. Results AMPAR2 and KA1 immunolocalised to remodelling bone, cartilage and synovial cells in human OA and RA, and rat AIA. All arthritic tissues showed degradation and synovial inflammation. NBQX reduced GluR abundance, knee swelling (parthritis. PMID:24130267

Differences in MRI findings between subgroups of recent-onset childhood arthritis

International Nuclear Information System (INIS)

Kirkhus, Eva; Flatoe, Berit; Smith, Hans-Joergen; Riise, Oeystein; Reiseter, Tor

2011-01-01

MRI is sensitive for joint inflammation, but its ability to separate subgroups of arthritis in children has been questioned. Infectious arthritis (IA), postinfectious arthritis (PA), transient arthritis (TA) and juvenile idiopathic arthritis (JIA) are subgroups that may need early, different treatment. To determine whether MRI findings differ in IA, PA/TA and JIA in recent-onset childhood arthritis. Fifty-nine children from a prospective study of incidence of arthritis (n = 216) were, based on clinical and biochemical criteria, examined by MRI. Joint fluid, synovium, bone marrow, soft tissue and cartilage were scored retrospectively and analysed by Pearson chi-square test and logistic regression analysis. Fifty-nine children had MRI of one station. IA was suggested by bone marrow oedema (OR 7.46, P = 0.011) and absence of T1-weighted and T2-weighted low signal intensity synovial tissue (OR 0.06, P = 0.015). Furthermore, soft-tissue oedema and reduced contrast enhancement in the epiphyses were more frequent in children with IA. JIA correlated positively with low signal intensity synovial tissue (OR 13.30, P < 0.001) and negatively with soft-tissue oedema (OR 0.20, P = 0.018). No significant positive determinants were found for PA/TA, but bone marrow oedema, soft-tissue oedema, irregular thickened synovium and low signal intensity synovial tissue was less frequent than in IA/JIA. In children with high clinical suspicion of recent onset arthritis, there was a significant difference in the distribution of specific MRI features among the diagnostic groups. (orig.)

Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis

NARCIS (Netherlands)

Noordenbos, Troy; Yeremenko, Nataliya; Gofita, Ioana; van de Sande, Marleen; Tak, Paul P.; Caňete, Juan D.; Baeten, Dominique

2012-01-01

Objective Studies comparing spondylarthritis (SpA) to rheumatoid arthritis (RA) synovitis suggest that innate immune cells may play a predominant role in the pathogenesis of SpA. Recent observations have indicated a marked synovial mast cell infiltration in psoriatic SpA. We therefore undertook the

Fetal Programming in Rheumatoid Arthritis

NARCIS (Netherlands)

F.D.O. de Steenwinkel (Florentien)

2013-01-01

markdownabstract__Abstract__ Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, autoimmune disease mainly affecting synovial tissues, which can lead to severe morbidity and progressive joint destruction resulting in deformations and disability. Other important outcomes include

MR findings of tuberculous arthritis; significance of tuberculoma

International Nuclear Information System (INIS)

Jang, Han Won; Kim, Jeen Woo; Cho, Kil Ho

2001-01-01

To determine the magnetic resonance (MR) imaging findings of tuberculous arthritis, and the frequency-in such cases-with which tuberculoma occurs. MR images of 26 patients (M;F, 14;12: mean age, 46.2 years) with pathologically proven tuberculous arthritis were retrospectively reviewed. The presence of joint effusion, subchondral erosion, synovial proliferation and soft tissue abscess, and whether the inner wall of this abscess was smooth, were assessed. In particular, we determined whether a nodular lesion which showed low SI on T1WI, central low SI with peripheral hjigh SI on T2WI, and rim enhancement on contrast study, was a tuberculoma. The joints involved were those of the knee (n=7), hip (n=7), shoulder (n=4), sacroiliac region (n=3), elbow (n=3), and ankle (n=2). Joint effusion was noted in 15 cases (58%), and subchondral erosion in 24 (92%). synovial proliferation was found in 23 cases (88%), and soft tissue abscess in 24 (92%). The inner wall of this abscess was irregular in 17 cases (71%). A tuberculoma was present in intra-or extra-or extra-articular soft tissue in 18 cases (69%). The MR findings of tuberculous arthritis were subchondral erosion, synovial proliferation, and soft tissue abscess. The presence of a tuberculoma in intra-or extra-articular soft tissue, a specific finding in tuberculous arthritis, was noted in 69% of our cases

MR findings of tuberculous arthritis; significance of tuberculoma

Energy Technology Data Exchange (ETDEWEB)

Jang, Han Won; Kim, Jeen Woo; Cho, Kil Ho [Yeungnam Univ. College of Medicine, Taegu (Korea, Republic of)

2001-02-01

To determine the magnetic resonance (MR) imaging findings of tuberculous arthritis, and the frequency-in such cases-with which tuberculoma occurs. MR images of 26 patients (M;F, 14;12: mean age, 46.2 years) with pathologically proven tuberculous arthritis were retrospectively reviewed. The presence of joint effusion, subchondral erosion, synovial proliferation and soft tissue abscess, and whether the inner wall of this abscess was smooth, were assessed. In particular, we determined whether a nodular lesion which showed low SI on T1WI, central low SI with peripheral hjigh SI on T2WI, and rim enhancement on contrast study, was a tuberculoma. The joints involved were those of the knee (n=7), hip (n=7), shoulder (n=4), sacroiliac region (n=3), elbow (n=3), and ankle (n=2). Joint effusion was noted in 15 cases (58%), and subchondral erosion in 24 (92%). synovial proliferation was found in 23 cases (88%), and soft tissue abscess in 24 (92%). The inner wall of this abscess was irregular in 17 cases (71%). A tuberculoma was present in intra-or extra-or extra-articular soft tissue in 18 cases (69%). The MR findings of tuberculous arthritis were subchondral erosion, synovial proliferation, and soft tissue abscess. The presence of a tuberculoma in intra-or extra-articular soft tissue, a specific finding in tuberculous arthritis, was noted in 69% of our cases.

Value of CT scan in synovial diseases

International Nuclear Information System (INIS)

Tamisier, J.N.; Regent, D.; Thomas, P.; Pere, P.; Gaucher, A.; Capesius, P.

1986-01-01

The authors have developed a technique of CT arthroscan which, by the use of a gas or opaque contrast medium, is able to demonstrate the synovial structures of the knee, the shoulder and the hip. Among the essential indications, they include the demonstration of neoplasia of the synovium and the evaluation of the pannus in rheumatoid arthritis. Their secondary indications include the demonstration of fluid effusions in the hip, the precise evaluation of hyperostotic lesions in the same joint, the detection of ossification phenomena in the capsule of the inter-apophyseal joints in ankylosing spondylitis and, in some cases, following negative or doubtful arthrography for the detection of synovial plica. They also recall the usefulness or the arthroscan in the diagnosis of lesions of the labrum glenoidale [fr

Is early rheumatoid arthritis the same disease process as late rheumatoid arthritis?

NARCIS (Netherlands)

Tak, P. P.

2001-01-01

Thoughts on treatment for the early control of synovitis have stimulated research on pathobiological events at the site of inflammation in patients with early rheumatoid arthritis. Several studies have thus been conducted to examine synovial biopsy samples at various stages of the disease. The most

SYNOVIAL MEMBRANE CHANGES IN PATIENTS WITH RHEUMATOID ARTHRITIS REVEALED DURING ARTHROSCOPY

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E. B. Komarova

2017-01-01

Full Text Available Exudative or proliferative processes accompanied by joint destruction may predominate in the synovial membrane (SM in different stages of rheumatoid arthritis (RA. The features of SM changes should be considered in the early diagnosis of RA and in the development of combination treatment for this disease.Objective: to study arthroscopic SM changes in patients with different RA durations and different blood anti-cyclic citrullinated peptide (anti-CCP antibody levels.Subjects and methods. 37 patients with RA underwent arthroscopy with an arthroscope of a 2.4-mm diameter and 30° angle (Karl Storz GmbH, Germany. RA duration was <2 years in 17 patients and ranged from 2 to 8 years in 20; the blood level of anti-CCP antibodies did not exceed 60 IU/ml in 15 patients and it was higher in 22. SM changes were assessed by a semiquantitative method.Results and discussion. Arthroscopy revealed a preponderance of SM hyperemia with an increased vascular pattern (p<0.01 and fibrin deposits (p<0.05 in patients with a RA duration of < 2 years and that of villous hyperplasia with the formation of club-shaped villi (p<0.05 in those with a RA duration of >2 years. The increase in anti-CCP by >60 U/ml was associated with a predominance of inflammatory hyperplasia (p < 0.01, SM hyperemia with a pronounced vascular pattern (p<0.05, as well as with the presence of pannus (pp<0.01.

Protective effects of methanolic extract of Adhatoda vasica Nees leaf in collagen-induced arthritis by modulation of synovial toll-like receptor-2 expression and release of pro-inflammatory mediators

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Rana Adhikary

2016-03-01

Full Text Available RA associated with oxidative stress and chronic inflammation has been a major health problem among the population worldwide. In this study protective effect of methanolic extract of Adhatoda vasica leaf (AVE was evaluated on Collagen-induced arthritis in male Swiss albino mice. Post oral administration of AVE at 50, 100 and 200 mg/kg body weight doses decreased the arthritic index and footpad swelling. AVE administration diminished pro-inflammatory cytokines in serum and synovial tissues. Reduced chemokines and neutrophil infiltration in synovial tissues after AVE administration dictated its protective effect against RA. Decreased LPO content and SOD activity along with concomitant rise in GSH and CAT activities from liver, spleen and synovial tissues indicated regulation of oxidative stress by AVE. In addition decreased CRP in serum along with suppressed TLR-2 expression in CIA mice after AVE treatment was also observed. Protective effect of AVE in RA is further supported from histopathological studies which showed improvement during bone damage. In conclusion this study demonstrated A. vasica is capable of regulating oxidative stress during CIA and therefore down regulated local and systemic release of pro-inflammatory mediators, which might be linked to mechanism of decreasing synovial TLR-2 expression via downregulating release of its regular endogenous ligands like CRP.

Fibroblastic rheumatism

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Jyoti Ranjan Parida

2017-01-01

Full Text Available Fibroblastic rheumatism (FR is a rare dermoarthopathy reported from different parts of the world since 1980. Although the exact cause is unknown, few reports implicate infection may be a triggering event. Patients usually present with multiple skin nodules and polyarthropathy with progressive skin contractures. Laboratory parameters including acute phase reactants are usually normal. The confirmatory diagnosis is based on histopathologic study of skin nodules, which demonstrate fibroblastic proliferation, thickened collagen fibers, dermal fibrosis, and decreased number of elastic fibers. Immunoreactivity for b-catenin, smooth muscle actin, and the monoclonal antibody HHF35 show myofibroblastic differentiation. Treatments with oral prednisolone and other disease-modifying drugs such as methotrexate, infliximab, and interferon have been tried with variable success. In general, skin lesions respond more aptly than joint symptoms indicating that skin fibroblast is more amenable to treatment than synovial fibroblasts. Awareness regarding this orphan disease among clinicians and pathologists will help in more reporting of such cases and finding out optimal treatment regimen.

Effects of yttrium 90 on experimental allergic arthritis in rabbits

International Nuclear Information System (INIS)

Meier-Ruge, W.; Mueller, W.; Pavelka, K.

1976-01-01

Fifteen weeks after allergic arthritis developed in the knee joint of 17 immunized rabbits, 8 animals were given an injection of 200 μCi yttrium 90( 90 Y) into the left joint cavity and 7 were injected with 400 μCi. The animals were sacrificed at 2, 4, 8, 12, and 16 weeks, and at 6 to 12 months after the injection. Two uninjected animals used as morphological controls were sacrificed 13 weeks after immunization, and showed allergic arthritis had progressed to severe inflammation of the knee joint marked by massive round-cell infiltration, oedema, and proliferation of synovial mesothelium in the synovial villi and joint capsule. Treatment with 90 Y was effective 2 weeks after injection and the disappearance of inflammatory odema and marked regression of round-cell infiltration. This was accompanied by degeneration of the synovial mesothelium and fibrosis of the subsynovial tissue and synovial vessels as a secondary effect of the radiation. In the animals with severe allergic arthritis, the healing effects of 90 Y were more marked than the secondary effects of the radiation which were dose-dependent. Treatment with 90 Y of arthritic knee joints with the lowest effective dose of the isotope - if necessay with repeated application - seems justified. A single large dose does not have a greater therapeutic effect and causes more radiation damage to the joint. In view of the possible secondary effects in the joint, the indication for 90 Y therapy should be restricted, particularly in young patients, to cases of chronic relapsing arthritis unresponsive to other treatment. (U.K.)

Effects of yttrium 90 on experimental allergic arthritis in rabbits

Energy Technology Data Exchange (ETDEWEB)

Meier-Ruge, W [Sandoz A.G., Basel (Switzerland); Mueller, W; Pavelka, K

1976-02-01

Fifteen weeks after allergic arthritis developed in the knee joint of 17 immunized rabbits, 8 animals were given an injection of 200 ..mu..Ci yttrium 90(/sup 90/Y) into the left joint cavity and 7 were injected with 400 ..mu..Ci. The animals were sacrificed at 2, 4, 8, 12, and 16 weeks, and at 6 to 12 months after the injection. Two uninjected animals used as morphological controls were sacrificed 13 weeks after immunization, and showed allergic arthritis had progressed to severe inflammation of the knee joint marked by massive round-cell infiltration, oedema, and proliferation of synovial mesothelium in the synovial villi and joint capsule. Treatment with /sup 90/Y was effective 2 weeks after injection and the disappearance of inflammatory odema and marked regression of round-cell infiltration. This was accompanied by degeneration of the synovial mesothelium and fibrosis of the subsynovial tissue and synovial vessels as a secondary effect of the radiation. In the animals with severe allergic arthritis, the healing effects of /sup 90/Y were more marked than the secondary effects of the radiation which were dose-dependent. Treatment with /sup 90/Y of arthritic knee joints with the lowest effective dose of the isotope - if necessay with repeated application - seems justified. A single large dose does not have a greater therapeutic effect and causes more radiation damage to the joint. In view of the possible secondary effects in the joint, the indication for /sup 90/Y therapy should be restricted, particularly in young patients, to cases of chronic relapsing arthritis unresponsive to other treatment.

Tuberculous arthritis and monoarticular rheumatoid arthritis in the knee : differential diagnosis using MR imaging

International Nuclear Information System (INIS)

Lim, Yeon Soo; Park, Jeong Mi; Shinn, Kwang Heun; Jee, Won Hee; Kim, Jee Young; Chun, Kyung Ah; Lee, Jae Mun

1999-01-01

To determine the extent to which magnetic resonance(MR) imaging findings can help differentiate between tuberculous arthritis (TA) and rheumatoid arthritis(RA). This study involved sixteen patients with pathologically proven arthritis of the knee. In eight patients(mean age, 29.6 years; M:F=4:4) this was of the tuberculous variety, while eight (mean age, 47.5 years; M:F=2:6) suffered from the rheumatoid variety, which was monoarticular. For 14 patients, contrast enhancement studies were available. We retrospectively analyzed MR findings according to the demonstrated pattern of synovial thickening (regular and even, or irregular and nodular), bone erosion or abscess, bone marrow(BM) edema, the sites at which bursae were present, para-articular mass formation, and lymphadenopathy. In five of eight TA cases (62.5%), irregular and nodular enhanced synovial thickening was present, while in six of eight RA cases (75%), thickening was regular and even. Bone erosions or subarticular abscesses were found in six TA cases (75%) and small erosions in three cases (37.5%) of RA. BM edema surrounding the erosion was found in four cases of TA (50%) and two of RA (25%). In TA, edema was more extensive. In both TA and RA, all suprapatella bursae were distended while popliteal bursae were present in two cases of TA (25%) and four of RA (50%). Para-articular masses with rim like enhancement were found in six cases of TA (75%) and in one case of RA (12.5%). In particular, para-articular lymphadenopathy was seen in six cases of TA (75%), but not in RA. MR findings of irregular and nodular synovial thickening, extensive bone erosion, extensive BM edema, particular, para-articular abscess formation and lymphadenopathy, may help differentiate tuberculous arthritis of the knee from the rhumatoid variety

Characterization of nitrotyrosine as a biomarker for arthritis and joint injury

DEFF Research Database (Denmark)

Misko, T P; Radabaugh, M R; Highkin, M

2013-01-01

OBJECTIVES: To characterize the utility of nitrotyrosine (NT) as a biomarker for arthritis and joint injury. DESIGN: Synovial fluid, plasma, and urine from patients diagnosed with osteoarthritis (OA), rheumatoid arthritis (RA), anterior cruciate ligament (ACL) injury, meniscus injury and pseudogout...

A computer-aided detection system for rheumatoid arthritis MRI data interpretation and quantification of synovial activity

International Nuclear Information System (INIS)

Kubassova, Olga; Boesen, Mikael; Cimmino, Marco A.; Bliddal, Henning

2010-01-01

Rational and objective: Disease assessment and follow-up of rheumatoid arthritis (RA) patients require objective evaluation and quantification. Magnetic resonance imaging (MRI) has a large potential to supplement such information for the clinician, however, time spent on data reading and interpretation slow down development in this area. Existing scoring systems of especially synovitis are too rigid and insensitive to measure early treatment response and quantify inflammation. This study tested a novel automated, computer system for analysis of dynamic MRI data acquired from patients with RA, Dynamika-RA, which incorporates efficient data processing and analysis techniques. Materials and methods: 140 MRI scans from hands and wrists of 135 active RA patients and 5 healthy controls were processed using Dynamika-RA and evaluated with RAMRIS. To reduce patient motion artefacts, MRI data were processed using Dynamika-RA, which removed motion in 2D and 3D planes. Then synovial enhancement was visualised and qualified using a novel fully automated voxel-by-voxel analysis based algorithm. This algorithm was used to replace traditional region-of-interest (ROI) and subtraction methods, yielding observer independent quantitative results. Results: Conventional scoring performed by an observer took 30-45 min per dataset. Dynamika-RA reduced motion artefacts, visualised inflammation and quantified disease activity in less than 3 min. Data processing allowed increasing signal to noise ratio by a factor 3. Due to fully automated procedure of data processing, there was no intertest variation in the results. Conclusions: Algorithms incorporated into Dynamika-RA allow for the significant enhancement of data quality through eliminating motion artefacts and reduction of time for evaluation of synovial inflammation.

Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis. A promising imaging biomarker as an alternative to gadolinium-based contrast agents

International Nuclear Information System (INIS)

Barendregt, Anouk M.; Gulik, E.C. van; Lavini, Cristina; Nusman, Charlotte M.; Hemke, Robert; Maas, Mario; Berg, J.M. van den; Schonenberg-Meinema, Dieneke; Kuijpers, Taco W.; Dolman, Koert M.

2017-01-01

To compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA). Regions of interest (ROI) were drawn in the synovium of JIA patients on T1 DCE and T2 DWI, followed by extraction of the maximum enhancement (ME), maximum initial slope (MIS), time to peak (TTP), % of different time intensity curve shapes (TIC) and apparent diffusion coefficient (ADC) of the ROIs. Mann-Whitney-U test was used for comparing parameters between MRI-active and -inactive patients (defined by the juvenile arthritis MRI scoring system). Spearman's rank was used to analyse the correlation between DCE and DWI. Thirty-five JIA patients (18 MRI active and 17 MRI inactive) were included. Median age was 13.1 years and 71% were female. ME, MIS, TTP, % TIC 5 and ADC were significantly different in MRI-active versus MRI-inactive JIA with median ADC 1.49 x 10 -3 mm 2 /s in MRI-active and 1.25 x 10 -3 mm 2 /s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 x 10 -3 mm 2 /s. ADC correlated to ME, MIS and TIC 5 shapes (r = 0.62, r = 0.45, r = -0.51, respectively, all p < 0.05). Similar to DCE parameters, DWI-derived ADC is significantly different in MRI-active JIA as compared to MRI-inactive JIA. The non-invasiveness of DWI combined with its possibility to detect synovial inflammation shows the potential of DWI. (orig.)

Clonal dominance among T-lymphocyte infiltrates in arthritis

International Nuclear Information System (INIS)

Stamenkovic, I.; Stegagno, M.; Wright, K.A.; Krane, S.M.; Amento, E.P.; Colvin, R.B.; Duquesnoy, R.J.; Kurnick, J.T.

1988-01-01

Synovial membranes in patients with rheumatoid arthritis as well as other types of chronic destructive inflammatory arthritis contain infiltrates of activated T lymphocytes that probably contribute to the pathogenesis of the disease. In an effort to elucidate the nature of these infiltrates, interleukin 2 (IL-2)-responsive T lymphocytes were grown out of synovial fragments from 14 patients undergoing surgery for advanced destructive inflammatory joint disease. Eleven of the samples examined were from patients with classical rheumatoid arthritis, while three others were obtained from individuals with clinical osteoarthritis. Southern blot analysis of T-cell receptor (TCR) β-chain genes in 13 of 14 cultures showed distinct rearrangements, indicating that each culture was characterized by the predominance of a limited number of clones. T-cell populations from peripheral blood stimulated with a variety of activators and expanded with IL-2 did not demonstrate evidence of similar clonality in long-term culture. These results suggest that a limited number of activated T-cell clones predominate at the site of tissue injury in rheumatoid synovial membranes as well as in other types of destructive inflammatory joint disease. Further characterization of these T-cell clones may aid our understanding of the pathogenesis of these rheumatic disorders

Radiological manifestations of rheumatoid arthritis; Die radiologische Manifestation der rheumatoiden Arthritis

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Kapp, H.J. [Zentrum fuer Rheumatologie, Schlangenbad (Germany). Abt. Radiologie

1997-06-01

Rheumatoid arthritis preferrably becomes manifest at the synovial joints of the limbs, especially at the small joints of the hands and feet, at bursae and synovial sheathes. The pathologic lesions are less frequently found at cartilaginous joints or entheses. The lesions very often are symmetrically distributed and are characterized by the following: 1. A periarticular, spindle-shaped opacity with a density similar to soft-tissue, induced by an inflammatory hypertrophy of the synovia, a serosynovitis, or an edematous impregnation of the periarticular tissue. 2. A juxta-articular osteoporosis, most probably caused by a neighbouring synovialitis accompanied by hyperemia. 3. A diffuse joint cavity narrowing due to a destruction of the articular cartilage by the pannus, a fibrovascular resorptive tissue. 4. Central as well as marginal erosions, caused by destruction of ossous material by the pannus. 5. Subchondral signal cysts, likewise unduced by the pannus. (Orig./AJ) [Deutsch] Die rheumatoide Arthritis manifestiert sich bevorzugt an den synovialen Gelenken der Extremitaeten, insbesondere an den kleinen Gelenken der Haende und Fuesse, an Bursae und an Sehnenscheiden. Seltener finden sich pathologische Veraenderungen an kartilaginaeren Gelenken und an Enthesen. Die Gelenkveraenderungen an Haenden und Fuessen sind oft symmetrisch verteilt und durch folgende Veraenderungen gepraegt: 1. Einer partikulaeren, spindelfoermigen weichteildichten Verschattung, hervorgerufen durch eine entsuendliche Hypertrophie der Synovia, einen Gelenkerguss und einer oedematoesen Durchtraenkung des perartikulaeren Gewebes. 2. Einer gelenknahen Osteoporose, deren Ursache die benachbarte Synovialitis mit Hyperaemie sein duerfte. 3. Einer diffusen Gelenkspaltverschmaelerung des Gelenkknorpels durch den Pannus, einem fibrovaskulaeren Resorptivgewebe. 4. Durch zentrale und marginale Erosionen, die als Folge einer Zerstoerung des Knochens durch den Pannus hervorgerufen werden. 5. Durch

Effects of Extract from Mangifera indica Leaf on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats

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Jiang, Yan; You, Xiao-Ying; Fu, Kong-Long; Yin, Wan-Le

2012-01-01

The leaves of Mangifera indica L. (Anacardiaceae) is used as a medicinal material in traditional herb medicine for a long time in India, China, and other Eastern Asian countries. Our present study investigated the therapeutic effects of the ethanol extract from Mangifera indica (EMI) in rat with monosodium urate (MSU) crystals-induced gouty arthritis. Effects of EMI (50, 100, and 200 mg/kg, p.o.) administrated for 9 days on the ankle swelling, synovial tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β) levels were assessed in MSU crystal rat. Data from our study showed that rat with gouty arthritis induced by MSU crystal demonstrated an elevation in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. Oral administration of 100 and 200 mg/kg EMI for 9 days reversed the abnormalities in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. The results indicated that the beneficial antigouty arthritis effect of EMI may be mediated, at least in part, by inhibiting TNF-α and IL-1β expression in the synovial tissues. Our study suggests that Mangifera indica and its extract may have a considerable potential for development as an anti-gouty arthritis agent for clinical application. PMID:23304232

Serodiagnosis and immune profile in rheumatoid arthritis.

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Chakraborty, P; Bhattacharya, S; Chakraborty, M; Pal, B

1997-11-01

One hundred and seventy-five cases of clinically diagnosed rheumatoid arthritis, 82 non-rheumatoid cases suffering from various other diseases and 40 healthy normal controls were investigated for detection of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of antinuclear antibody (ANA) and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor (RF) showed 64% positivity in rheumatoid group and 1.2% positivity in non-rheumatoid group. All three immunoglobulins (IgG, IgM, IgA) were found to be raised in serum of patients with rheumatoid arthritis, whereas only IgA level was elevated in serum of patients with non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 3.4% and 2.8% cases respectively in cases of clinically diagnosed rheumatoid arthritis who had been suffering from severe active rheumatoid arthritis. In non-rheumatoid group RF was positive in significant titre in only one case of leprosy. Synovial fluid and synovium were found to be heavily infiltrated by plasma cells and lymphocytes. RF appears first in synovial fluid and then in serum. Hence RF titre in blood may not attain significant level for the first several months.

Basic calcium phosphate crystal-induced Egr-1 expression stimulates mitogenesis in human fibroblasts

International Nuclear Information System (INIS)

Zeng, Xiao R.; Sun Yubo; Wenger, Leonor; Cheung, Herman S.

2005-01-01

Previously, we have reported that basic calcium phosphate (BCP) crystals stimulate mitogenesis and synthesis of matrix metalloproteinases in cultured human foreskin and synovial fibroblasts. However, the detailed mechanisms involved are still unclear. In the present study, using RT-PCR and Egr-1 promoter analysis we showed that BCP crystals could stimulate early growth response gene Egr-1 transcription through a PKCα-dependent p44/p42 MAPK pathway. Using a retrovirus gene expression system (Clontech) to overexpress Egr-1 in human fibroblast BJ-1 cells resulted in promotion of mitogenesis measured either by MTT cell proliferation analysis or by direct cell counting. The results demonstrate that Egr-1 may play a key role in mediating BCP crystal-induced synovial fibroblast mitogenesis

[Proteus mirabilis septic arthritis].

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Sbiti, Mohammed; Bouhamidi, Bahia; Louzi, Lhoussaine

2017-01-01

Acute septic arthritis is rare. It is associated with poor prognosis in terms of mortality and morbidity. We report the case of a 61-year old patient with spontaneous Proteus mirabilis septic arthritis. He suffered from complicated diabetes associated with positive blood cultures and synovial fluid cultures. Patient's evolution was favorable thanks to early diagnosis and initiation of adequate antibiotic therapy. Proteus mirabilis septic arthritis is rare. On that basis we conducted a literature review of cases of Proteus mirabilis pyogenic arthritis to highlight the risk factors, pathogenesis, treatment and evolution of these diseases. Diagnosis is commonly based on microbiological analysis, early articular puncture biopsy is performed before the initiation of antibiotic treatment, direct examination, culture and antibiogram which are useful as guidance for antibiotic therapy. Septic arthritis is a diagnostic and therapeutic emergency; early management of this disease allows total healing without after-effects.

Synovial tissue rank ligand expression and radiographic progression in rheumatoid arthritis: observations from a proof-of-concept randomized clinical trial of cytokine blockade.

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Rooney, Terence

2012-02-01

The objective of the study was to evaluate synovial tissue receptor activator of nuclear factor-kappabeta ligand (RANKL) and osteoprotegerin (OPG) as biomarkers of disease activity, progressive joint damage, and therapeutic response, during cytokine blockade in rheumatoid arthritis (RA). Patients with active RA entered a randomized open-label 12-month study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 mug\\/kg twice weekly. Arthroscopic synovial tissue biopsies were obtained at baseline, at 4 weeks and at the final time point. Following immunohistochemical staining, RANKL and OPG expression was quantified using digital image analysis. Radiographic damage was evaluated using the van der Heijde modification of the Sharp scoring system. Twenty-two patients were randomized. Baseline expression of RANKL, but not OPG, correlated significantly with baseline CRP levels (r = 0.61, P < 0.01). While a significant reduction in OPG expression following treatment was observed in clinical responders at the final time point (P < 0.05 vs. baseline), RANKL levels did not change, and the RANKL:OPG ratio remained unaltered, even at the highest levels of clinical response. When potential predictors of radiographic outcome were evaluated, baseline RANKL expression correlated with erosive progression at 1 year (r = 0.71, P < 0.01). Distinct, though related, pathophysiologic processes mediate joint inflammation and destruction in RA. Elevated synovial tissue RANKL expression is associated with progressive joint erosion, and may be independent of the clinical response to targeted therapy. The potential therapeutic importance of modulating RANKL in RA is highlighted, if radiographic arrest is to be achieved.

Electroacupuncture Inhibits Inflammation Reaction by Upregulating Vasoactive Intestinal Peptide in Rats with Adjuvant-Induced Arthritis

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Tian-Feng He

2011-01-01

Full Text Available Acupuncture is emerging as an alternative therapy for rheumatoid arthritis (RA. However, the molecular mechanism underlying this beneficial effect of acupuncture has not been fully understood. Here, we demonstrated that electroacupuncture at acupoints Zusanli (ST36, Xuanzhong (GB39; and Shenshu (BL23 markedly decreased the paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced the body weight loss in an adjuvant-induced arthritis rat model. However, the electrical stimulation at nonacupoint did not produce any beneficial effects against the experimental arthritis. Most interestingly, the electroacupuncture treatment resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP, a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was significantly negatively correlated with the scores of inflammation in the synovial tissue (r=−0.483, P=.0026. In conclusion, these findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of RA, at least partially through the induction of VIP expression.

Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis. A promising imaging biomarker as an alternative to gadolinium-based contrast agents

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Barendregt, Anouk M.; Gulik, E.C. van [Academic Medical Center/University of Amsterdam, Department of Radiology, Amsterdam (Netherlands); Academic Medical Center/University of Amsterdam, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children' s Hospital, Amsterdam (Netherlands); Lavini, Cristina; Nusman, Charlotte M.; Hemke, Robert; Maas, Mario [Academic Medical Center/University of Amsterdam, Department of Radiology, Amsterdam (Netherlands); Berg, J.M. van den; Schonenberg-Meinema, Dieneke; Kuijpers, Taco W. [Academic Medical Center/University of Amsterdam, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children' s Hospital, Amsterdam (Netherlands); Dolman, Koert M. [Reade, Department of Pediatric Rheumatology, Amsterdam (Netherlands); Onze Lieve Vrouwe Gasthuis West, Department of Pediatric Rheumatology, Amsterdam (Netherlands); Onze Lieve Vrouwe Gasthuis Oost, Department of Pediatric Rheumatology, Amsterdam (Netherlands)

2017-11-15

To compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA). Regions of interest (ROI) were drawn in the synovium of JIA patients on T1 DCE and T2 DWI, followed by extraction of the maximum enhancement (ME), maximum initial slope (MIS), time to peak (TTP), % of different time intensity curve shapes (TIC) and apparent diffusion coefficient (ADC) of the ROIs. Mann-Whitney-U test was used for comparing parameters between MRI-active and -inactive patients (defined by the juvenile arthritis MRI scoring system). Spearman's rank was used to analyse the correlation between DCE and DWI. Thirty-five JIA patients (18 MRI active and 17 MRI inactive) were included. Median age was 13.1 years and 71% were female. ME, MIS, TTP, % TIC 5 and ADC were significantly different in MRI-active versus MRI-inactive JIA with median ADC 1.49 x 10{sup -3} mm{sup 2}/s in MRI-active and 1.25 x 10{sup -3} mm{sup 2}/s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 x 10{sup -3} mm{sup 2}/s. ADC correlated to ME, MIS and TIC 5 shapes (r = 0.62, r = 0.45, r = -0.51, respectively, all p < 0.05). Similar to DCE parameters, DWI-derived ADC is significantly different in MRI-active JIA as compared to MRI-inactive JIA. The non-invasiveness of DWI combined with its possibility to detect synovial inflammation shows the potential of DWI. (orig.)

Involvement of interleukin-8 in dialysis-related arthritis.

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Takayama, F; Miyazaki, T; Aoyama, I; Tsukushi, S; Sato, M; Yamazaki, C; Shimokata, K; Niwa, T

1998-04-01

To elucidate the role of interleukin (IL)-8, a chemotactic factor for neutrophils, in dialysis-related arthritis (DRA) of patients on long-term hemodialysis, the concentration of IL-8 was measured in the synovial fluids of DRA patients with acute arthralgia and joint swelling, and was compared with those in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). We noted a marked elevation of IL-8 in the joint fluids of patients with DRA and RA as compared with OA. Furthermore, to determine the role of IL-8 in synovitis, we examined the in vivo effect of intra-articular injection of human recombinant IL-8 on leukocyte infiltration into the joint space of rabbits. A single injection of IL-8 to the joints of rabbits induced rapid infiltration of neutrophils into the joint space and synovial tissues, which reached a maximum in four hours. The oral administration of indometacin farnesil (a prodrug that is converted to indomethacin after intestinal absorption) before the injection of IL-8 alleviated the infiltration of neutrophils. When human synovial cells were incubated with tumor necrosis factor (TNF)-alpha, the expression of IL-8 mRNA and IL-8 production in the cultured synovial cells were increased. The TNF-alpha-stimulated expression of IL-8 mRNA and IL-8 production in the cultured synovial cells were markedly inhibited by dexamethasone. In conclusion, IL-8 levels were markedly elevated in the joint fluids of patients with DRA. Interleukin-8 released from synovial cells may be an important factor to induce acute inflammation in DRA. Dexamethasone and indomethacin may be effective for DRA by inhibiting the production and chemotactic actions of IL-8, respectively.

Scoring ultrasound synovitis in rheumatoid arthritis

DEFF Research Database (Denmark)

Terslev, Lene; Naredo, Esperanza; Aegerter, Philippe

2017-01-01

OBJECTIVES: To test the reliability of new ultrasound (US) definitions and quantification of synovial hypertrophy (SH) and power Doppler (PD) signal, separately and in combination, in a range of joints in patients with rheumatoid arthritis (RA) using the European League Against Rheumatisms...

IL-15 expression on RA synovial fibroblasts promotes B cell survival.

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Marta Benito-Miguel

Full Text Available INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001. IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05. Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

Locomotion and muscle mass measures in a murine model of collagen-induced arthritis

NARCIS (Netherlands)

Hartog, A.; Hulsman, J.; Garssen, J.

2009-01-01

Background: Rheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and

Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1beta.

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Dulos, John; Verbraak, Evert; Bagchus, Wilma M; Boots, Annemieke M H; Kaptein, Allard

2004-10-01

The endogenous steroid dehydroepiandrosterone (DHEA) has been reported to play a role in rheumatoid arthritis (RA). DHEA is metabolized by the P450 enzyme CYP7B into 7alpha-OH-DHEA, which has immunostimulating properties. This study was undertaken to investigate the putative role of CYP7B in arthritis using murine collagen-induced arthritis (CIA), an interleukin-1beta (IL-1beta)-dependent model. DBA/1J mice were immunized and administered a booster with type II collagen. The presence of 7alpha-OH-DHEA was determined in both arthritic and nonarthritic joints and the serum of CIA mice by radioimmunoassay. CYP7B messenger RNA (mRNA) expression was analyzed in synovial biopsy samples, and in fibroblast-like synoviocytes (FLS) isolated from these synovial biopsy samples, by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the regulatory role of IL-1beta on CYP7B activity in FLS was determined using RT-PCR, Western blotting, and high-performance liquid chromatography. In knee joint synovial biopsy samples from arthritic mice, 7alpha-OH-DHEA levels were 5-fold higher than in nonarthritic mice. Elevated levels of 7alpha-OH-DHEA were accompanied by an increase in CYP7B mRNA expression and were positively correlated with disease severity. In serum, no differences in 7alpha-OH-DHEA levels were observed between arthritic and nonarthritic mice. Incubation of FLS with IL-1beta resulted in a dose-dependent increase in 7alpha-OH-DHEA formation. In addition, IL-1beta enhanced CYP7B mRNA and CYP7B protein levels in FLS. Disease progression in CIA is correlated with enhanced CYP7B activity, which leads to locally enhanced 7alpha-OH-DHEA levels. Elevated IL-1beta levels within the arthritic joint may regulate this increase in CYP7B activity. Copyright 2004 American College of Rheumatology

Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks

DEFF Research Database (Denmark)

Andersen, Martin; Boesen, Mikael; Ellegaard, Karen

2014-01-01

was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans. METHODS: RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic.......02, approximate Spearman's ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance. CONCLUSIONS: The association between imaging activity and synovial inflammatory mediators underscores the high sensitivity of CDUS and MRI in the evaluation of RA disease activity....... The associations found in our present study have different implications for synovial mediator releases and corresponding imaging signs. For example, MCP-1 and IL-6 were associated with both general inflammation and bone destruction, in contrast to MIP-1β, which was involved solely in general synovitis. The lack...

Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy

NARCIS (Netherlands)

Baeten, Dominique; Kruithof, Elli; de Rycke, Leen; Boots, Anemieke M.; Mielants, Herman; Veys, Eric M.; de Keyser, Filip

2005-01-01

Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features of synovium reflect specific phenotypes

Different approaches to synovial membrane volume determination by magnetic resonance imaging: manual versus automated segmentation

DEFF Research Database (Denmark)

Østergaard, Mikkel

1997-01-01

Automated fast (5-20 min) synovial membrane volume determination by MRI, based on pre-set post-gadolinium-DTPA enhancement thresholds, was evaluated as a substitute for a time-consuming (45-120 min), previously validated, manual segmentation method. Twenty-nine knees [rheumatoid arthritis (RA) 13...

Distinguishing Pediatric Lyme Arthritis of the Hip from Transient Synovitis and Acute Bacterial Septic Arthritis: A Systematic Review and Meta-analysis.

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Cruz, Aristides I; Anari, Jason B; Ramirez, Jose M; Sankar, Wudbhav N; Baldwin, Keith D

2018-01-25

Objective Lyme arthritis is an increasingly recognized clinical entity that often prompts orthopaedic evaluation in pediatric patients. While Lyme arthritis is most common in the knee, the clinical presentation of Lyme arthritis of the hip can be similar to both acute bacterial septic arthritis and transient synovitis. Accurately distinguishing these clinical entities is important since the definitive treatment of each is distinct. Because there is limited literature on monoarticular Lyme arthritis of the hip, the purpose of this study was to perform a systematic review and meta-analysis of clinical and laboratory parameters associated with Lyme arthritis (LA) of the hip and compare them to septic arthritis (SA) and transient synovitis (TS).  Study design A systematic review of the literature was performed using the following search terms, including the variants and plural counterparts "hip" and "Lyme arthritis." A final database of individual patients was assembled from the published literature and direct author correspondence, when available. A previously published cohort of patients with hip transient synovitis or septic arthritis was used for comparative analysis. A comparative statistical analysis was performed to the assembled database to assess differences in laboratory and clinical variables between the three diagnoses.  Results Data on 88 patients diagnosed with Lyme arthritis of the hip was collected and consolidated from the 12 articles meeting inclusion criteria. The average age of patients presenting with Lyme arthritis was 7.5 years (± 3.5 years), the mean erythrocyte sedimentation rate (ESR), and the C-reactive protein (CRP) was 41 mm/hr and 3.9 mg/L, respectively. Peripheral white blood cell (WBC) count averaged 10.6 x 10 9 cells/L with the synovial WBC count averaging 55,888 cells/mm 3 . Compared to a previous cohort of patients with confirmed transient synovitis or septic arthritis, the 95% confidence interval for ESR was 21 - 33 mm

Isolation of Chlamydia trachomatis or Ureaplasma urealyticum from the synovial fluid of patients with Reiter's syndrome

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Pavlica Ljiljana

2003-01-01

Full Text Available Background. The aim of this study was to contribute to the insight of the role of the infectious agent in ethiopathogenesis of the Reiter’s syndrome development, which could directly influence the choise of treatment of these patients. Methods. Eighteen patients with urogenital form of the Reiter’s syndrome and 16 controls (6 with rheumatoid arthritis and 10 with pigmented villonodular synovitis were included in the study. In all patients standard laboratory analyses of the blood, urine and stool were made; antibody titer to Chlamydia trachomatis and Ureaplasma urealyticum was determined in synovial fluid and serum; isolation of Chlamydia trachomatis and Ureaplasma urealyticum in urethral, cervical and conjunctival swabs, as well as in prostatic and synovial fluid, was also made. HLA typing was done, too. Chlamydia was isolated in the McCoy cell culture treated with cycloheximide while Ureaplasma was identified according to its biochemical properties grown on cell-free liquid medium. Results. Chlamydia trachomatis was isolated from the synovial fluid of 4 patients with Reiter's syndrome 22.2%, while Ureaplasma urealyticum was isolated in 7 of them (38.9%. These microorganisms were not found in any synovial fluid of the control group patients. Conclusion. Presence of these bacteria in the inflamed joint might be an important factor in etiopathogenesis of this disease, and it supports the hypothesis that arthritis in Reiter's syndrome is probably of the infectious origin.

Study for synovial lesions by MRI using gadolinium-DTPA (Gd-DTPA) in patients with early phase of rheumatoid arthritis

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Takano, Keiyu (Saint Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine)

1993-02-01

To evaluate the usefulness of magnetic resonanse imaging (MRI) enhanced with gadolinium-DTPA (Gd-DTPA) for the detection of the inflamed synovium and for the evaluation of the responce to therapy in rheumatoid arthritis, we studied 49 patients with rheumatoid arthritis (RA) according to the 1987 revised criteria of American Rheumatism Association (ARA), 6 patients with systemic lupus erythematosus (SLE) complicated by arthritis, 3 patients with osteoarthritis (OA), 2 patients with Sjoegren syndrome, 2 patients with progressive systemic sclerosis and 10 healthy volunteers as an age matched control. The 49 patients with RA were divided into three groups: (1) early phase of RA, (2) non progressing RA and (3) slowly progressing RA, and the stage classification of plain X-ray film and enhancement pattern of MR imaging were classified into three groups. Synovial enhancement showed a linear, band-like or diffuse pattern. Almost all cases in early phase of RA group and non progressing RA group showed a linear pattern, a band-like pattern or even no enhancement, while slowly progressing group of stage II or higher showed the diffuse pattern of enhancement in all except 2 cases. Moreover, the linear pattern, the band-like pattern or even no contrast enhancement were seen in all except 1 stage I patient, whereas 26 out of 29 patients with stage II or higher change showed diffuse contrast enhancement. Furthermore, a comparison of MR images before and after administration of disease modifying antirheumatic drugs (DMARDs) in 10 patients showed that the improvement of clinical symptomes correlated fairly well with reduction of contrast enhancement. The present study suggested that MRI of the wrist using Gd-DTPA enhancement may be useful for the diagnosis of RA, the prediction of articular damage, and judgement of the response to therapy. (author).

Notch-1 mediates hypoxia-induced angiogenesis in rheumatoid arthritis.

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Gao, Wei; Sweeney, Catherine; Connolly, Mary; Kennedy, Aisling; Ng, Chin Teck; McCormick, Jennifer; Veale, Douglas J; Fearon, Ursula

2012-07-01

To examine the effect of hypoxia on Notch-1 signaling pathway components and angiogenesis in inflammatory arthritis. The expression and regulation of Notch-1, its ligand delta-like protein 4 (DLL-4) and downstream signaling components (hairy-related transcription factor 1 [HRT-1], HRT-2), and hypoxia-inducible factor 1α (HIF-1α) under normoxic and hypoxic conditions (1-3%) were assessed in synovial tissue specimens from patients with inflammatory arthritis and controls and in human dermal microvascular endothelial cells (HDMECs) by immunohistology, dual immunofluorescence staining (Notch-1/factor VIII), Western blotting, and real-time polymerase chain reaction. In vivo synovial tissue oxygen levels (tissue PO2) were measured under direct visualization at arthroscopy. HDMEC activation under hypoxic conditions in the presence of Notch-1 small interfering RNA (siRNA), the γ-secretase inhibitor DAPT, or dimethyloxalylglycine (DMOG) was assessed by Matrigel tube formation assay, migration assay, invasion assay, and matrix metalloproteinase 2 (MMP-2)/MMP-9 zymography. Expression of Notch-1, its ligand DLL-4, and HRT-1 was demonstrated in synovial tissue, with the strongest expression localized to perivascular/vascular regions. Localization of Notch-1 to synovial endothelium was confirmed by dual immunofluorescence staining. Notch-1 intracellular domain (NICD) expression was significantly higher in synovial tissue from patients with tissue PO2 of PO2 of >20 mm Hg (>3% O2). Exposure of HDMECs to 3% hypoxia induced HIF-1α and NICD protein expression and DLL-4, HRT-1, and HRT-2 messenger RNA expression. DMOG directly induced NICD expression, while Notch-1 siRNA inhibited hypoxia-induced HIF-1α expression, suggesting that Notch-1/HIF-1α signaling is bidirectional. Finally, 3% hypoxia-induced angiogenesis, endothelial cell migration, endothelial cell invasion, and proMMP-2 and proMMP-9 activities were inhibited by Notch-1 siRNA and/or the γ-secretase inhibitor DAPT. Our

Psoriatic arthritis: from pathogenesis to therapy.

LENUS (Irish Health Repository)

Fitzgerald, Oliver

2012-02-01

Psoriatic arthritis is a multigenic autoimmune disease that involves synovial tissue, entheseal sites and skin, and that may result in significant joint damage. Although there are no diagnostic tests for psoriatic arthritis, research has identified consistent features that help to distinguish the condition from other common rheumatic diseases. Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis. T-cell receptor phenotypic studies have failed to identify antigen-driven clones, and an alternative hypothesis for CD8 stimulation involving innate immune signals is proposed. Finally, imaging studies have highlighted entheseal involvement in psoriatic arthritis, and it is possible that entheseal-derived antigens may trigger an immune response that is critically involved in disease pathogenesis.

Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis

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Bhupinder Kapoor

2014-01-01

Full Text Available The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs, corticosteroids, disease modifying antirheumatic drugs (DMARDs, and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology.

Serology and immunoglobulin profile in rheumatoid arthritis.

Science.gov (United States)

Adhya, S; Chakraborty, G; Hajra, B; Bhattacharya, S; Sikdar, P K; Sinha, S; Banerjee, P P; Ghosh, E; Chakraborty, P

1998-01-01

One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

Subacromial bursitis with giant rice bodies as initial presentation of rheumatoid arthritis.

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Subramaniam, Ramesh; Tan, Justina Wei Lyn; Chau, Cora Yuk Ping; Lee, Keng Thiam

2012-10-01

Rice body formation is a nonspecific response to chronic synovial inflammation associated with tuberculous arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, seronegative inflammatory arthritis, and even osteoarthritis. Such bodies were termed rice bodies because of their close resemblance to grains of polished white rice. We present a case report of a middle-aged woman with right shoulder subacromial/subdeltoid bursitis with giant rice body formation as her initial presentation of rheumatoid arthritis. Her right shoulder symptoms resolved after subacromial and subdeltoid bursectomy and removal of the rice bodies. She subsequently developed inflammatory arthritis of other joints, met the criteria for rheumatoid arthritis, and has been treated medically.

Pannus invasion and cartilage degradation in rheumatoid arthritis: involvement of MMP-3 and interleukin-1beta.

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Ainola, M M; Mandelin, J A; Liljeström, M P; Li, T F; Hukkanen, M V J; Konttinen, Y T

2005-01-01

Synovial inflammation in rheumatoid arthritis (RA) leads to pannus tissue invasion and destruction of cartilage/bone matrix by proteinases. Our intention was to analyze some of the key matrix metalloproteinases (MMPs) in pannus tissue overlying evolving cartilage erosions in RA. Frozen tissue samples of pannus and synovium from advanced RA and synovium from osteoarthritic patients were used for immunohistochemical, western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis of MMP-1, -3, -13 and -14. Synovial fibroblast cultures, stimulated with tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), were analyzed with enzyme-linked immunosorbent assays (ELISA) and quantitative RT-PCR. MMP-3 was highly expressed in pannus tissue compared with significantly lower expression levels of MMP-1, -13 and -14. In fibroblast cultures IL-1beta was a potent stimulus for MMP-3, whereas TNF-alpha was more potent for MMP-1. This is the first study to demonstrate quantitatively in real time that MMP-3 mRNA expression is clearly higher in advanced RA pannus tissue compared to parallel RA or osteoarthritic synovium. MMP-3 mRNA levels were also clearly overexpressed in RA pannus compared to MMP-1, -13 and -14. Advanced RA has previously been found to overexpress IL-1beta. The high expression of MMP-3 in pannus and IL-1beta, mediated stimulation of MMP-3 suggest that MMP-3 plays a significant role in the progression of erosions through the proteoglycan-rich cartilage matrix.

Folate-targeted nanoparticles for rheumatoid arthritis therapy.

Science.gov (United States)

Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

2016-05-01

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiological manifestations of rheumatoid arthritis

International Nuclear Information System (INIS)

Kapp, H.J.

1997-01-01

Rheumatoid arthritis preferrably becomes manifest at the synovial joints of the limbs, especially at the small joints of the hands and feet, at bursae and synovial sheathes. The pathologic lesions are less frequently found at cartilaginous joints or entheses. The lesions very often are symmetrically distributed and are characterized by the following: 1. A periarticular, spindle-shaped opacity with a density similar to soft-tissue, induced by an inflammatory hypertrophy of the synovia, a serosynovitis, or an edematous impregnation of the periarticular tissue. 2. A juxta-articular osteoporosis, most probably caused by a neighbouring synovialitis accompanied by hyperemia. 3. A diffuse joint cavity narrowing due to a destruction of the articular cartilage by the pannus, a fibrovascular resorptive tissue. 4. Central as well as marginal erosions, caused by destruction of ossous material by the pannus. 5. Subchondral signal cysts, likewise unduced by the pannus. (Orig./AJ) [de

Imbalanced expression of RANKL and osteoprotegerin mRNA in pannus tissue of rheumatoid arthritis.

Science.gov (United States)

Ainola, M; Mandelin, J; Liljeström, M; Konttinen, Y T; Salo, J

2008-01-01

To test if the pannus tissue is characterized by a high receptor activator of nuclear factor kappaB ligand to osteoprotegerin (RANKL:OPG) ratio, which could explain local osteoclastogenesis and formation of bony erosions. Messenger RNA and protein expressions of RANKL and OPG in rheumatoid and osteoarthritic tissue samples were measured using quantitative real-time RT-PCR and Western blot/densitometry. Pannus and synovitis fibroblasts explanted from tissue samples were cultured in vitro without and with TNF-alpha, IL-1Beta or IL-17 and analyzed quantitatively for RANKL expression. The ability of pannus fibroblasts to induce formation of multinuclear osteoclast-like cells from human monocytes, with macrophage-colony stimulating factor (M-CSF) but without RANKL added, was tested. Histochemical staining was used to assess the eventual presence of RANKL and tartrate resistant acid phosphatase positive osteoclast-like cells at the pannus-bone interface. RANKL:OPG ratios of messenger RNA (ppannus (2.06+/-0.73 and 2.2+/-0.65) compared to rheumatoid (0.62+/-0.13 and 1.31+/-0.69) and osteoarthritis (0.62+/-0.32 and 0.52+/-0.16) synovial membranes. Resting and stimulated (p dependent on the cytokine used) pannus fibroblasts produced RANKL in excess (p=0.0005) and unstimulated pannus fibroblasts also effectively induced osteoclast-like cell formation from monocytes in vitro without any exogenous RANKL added. Compatible with these findings, multinuclear osteoclasts-like cells were frequent in the fibroblast- and macrophage-rich pannus tissue at the soft tissue-to-bone interface. The high RANKL:OPG ratio, together with close fibroblast-to-monocyte contacts in pannus tissue, probably favor local generation of bone resorbing osteoclasts at the site of erosion in rheumatoid arthritis.

Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.

LENUS (Irish Health Repository)

Biniecka, Monika

2012-02-01

OBJECTIVES: To assess levels of oxidative DNA damage (8-oxo-7,8-dihydro-2\\'-deoxyguanine; 8-oxo-dG) and lipid peroxidation (4-hydroxy-2-nonenal; 4-HNE) in serum, synovial fluid and tissue of patients with inflammatory arthritis in relation to in vivo hypoxia levels, disease activity and angiogenic markers. METHODS: Oxygen levels in synovial tissue were assessed using an oxygen\\/temperature probe. Nuclear and cytoplasmic 8-oxo-dG and 4-HNE levels were assessed in synovial tissue from 23 patients by immunohistochemistry. 8-Oxo-dG and 4-HNE levels in serum and synovial fluid were determined using 8-oxo-dG and hexanoyl-Lys (HEL) adduct ELISAs, respectively. Serum vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) levels were also measured by ELISA. RESULTS: The median oxygen tension in synovial tissue was profoundly hypoxic at 19.35 mm Hg (2.5%). Nuclear 8-oxo-dG levels were significantly higher than nuclear 4-HNE levels in the lining and sublining layers (all p<0.001). In contrast, cytoplasmic 4-HNE levels were higher than cytoplasmic 8-oxo-dG levels in both cell layers (all p<0.001). Reduced in vivo oxygen tension correlated with high lipid peroxidation in synovial fluid (p=0.027; r=0.54) and tissue (p=0.004; r=0.58). Serum VEGF levels were positively correlated with cytoplasmic 4-HNE expression (p=0.05; r=0.43) and intensity (p=0.006; r=0.59) in the lining layer. Serum Ang2 levels were positively correlated with nuclear 4-HNE expression and intensity in both cell layers (all p < or = 0.05). DAS28-C-reactive protein was correlated with nuclear 4-HNE expression in the sublining layer (p=0.02; r=0.48) and DAS28-erythrocyte sedimentation rate was correlated with nuclear 4-HNE expression in both cell layers (p < or = 0.03). CONCLUSIONS: Lipid peroxidation is associated with low oxygen tension in vivo, disease activity and angiogenic marker expression in inflammatory arthritis.

Effect of Bizhongxiao decoction and its dismantled formulae on IL-1 and TNF levels in collagen-induced arthritis in rat synovial joints

Directory of Open Access Journals (Sweden)

Guo Ya-jing

2012-11-01

Full Text Available Abstract Background Rheumatoid arthritis (RA, a chronic autoimmune disease, affects sufferers in many different ways. Treatment of this chronic condition is particularly challenging. Traditional Chinese Medicine (TCM provides alternatives. Bizhongxiao decoction (BZX is a TCM complex, which has been used clinically for many years to treat RA. The purpose of this study is to compare the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels in rats with RA, and to elucidate its mechanism of action. Methods Ninety healthy normal female SD rats were randomly divided into six groups: normal (control, model, BZX decoction, and the three dismantled formulae (I: heat-clearing and detoxication, II: dissipating dampness, and III: blood circulation promotion. Apart from the normal (control group, the rats in each group were injected subcutaneously with bovine type II collagen and complete Freund adjuvant to establish a collagen-induced arthritis model, so that inhibition of foot swelling in the rats by BZX decoction and its dismantled formulae could be observed. Immunohistochemistry was used to assess the levels of the inflammatory cytokines IL-1 and TNF in synovial joints at various time points. Results Twenty-one days after the model was established, the levels of TNF and IL-1 were significantly higher in the model group, BZX decoction group and dismantled formula groups I, II and III than in the normal controls (P  Conclusions BZX decoction and the three dismantled formulae examined down-regulated the inflammatory factors IL-1 and TNF in collagen-induced arthritis rat models, but BZX exerted the strongest effect.

Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes.

Science.gov (United States)

Ai, Rizi; Laragione, Teresina; Hammaker, Deepa; Boyle, David L; Wildberg, Andre; Maeshima, Keisuke; Palescandolo, Emanuele; Krishna, Vinod; Pocalyko, David; Whitaker, John W; Bai, Yuchen; Nagpal, Sunil; Bachman, Kurtis E; Ainsworth, Richard I; Wang, Mengchi; Ding, Bo; Gulko, Percio S; Wang, Wei; Firestein, Gary S

2018-05-15

Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.

Mast cell depletion in the preclinical phase of collagen-induced arthritis reduces clinical outcome by lowering the inflammatory cytokine profile.

NARCIS (Netherlands)

Velden, van der D.; Lagraauw, H.M.; Wezel, A.; Launay, P.; Kuiper, J.; Huizinga, T.W.J.; Toes, R.E.M.; Bot, I.; Stoop, J.N.

2016-01-01

BACKGROUND Rheumatoid arthritis (RA) is a multifactorial autoimmune disease, which is characterized by inflammation of synovial joints leading to the destruction of cartilage and bone. Infiltrating mast cells can be found within the inflamed synovial tissue, however their role in disease

Sonoporation-mediated transduction of siRNA ameliorated experimental arthritis using 3 MHz pulsed ultrasound.

Science.gov (United States)

Inoue, Hiroaki; Arai, Yuji; Kishida, Tsunao; Shin-Ya, Masaharu; Terauchi, Ryu; Nakagawa, Shuji; Saito, Masazumi; Tsuchida, Shinji; Inoue, Atsuo; Shirai, Toshiharu; Fujiwara, Hiroyoshi; Mazda, Osam; Kubo, Toshikazu

2014-03-01

The goal of this feasibility study was to examine whether sonoporation assisted transduction of siRNA could be used to ameliorate arthritis locally. If successful, such approach could provide an alternative treatment for the patients that have or gradually develop adverse response to chemical drugs. Tumor necrosis factor alpha (TNF-α) produced by synovial fibroblasts has an important role in the pathology of rheumatoid arthritis, inducing inflammation and bone destruction. In this study, we injected a mixture of microbubbles and siRNA targeting TNF-α (siTNF) into the articular joints of rats, and transduced siTNF into synovial tissue by exposure to a collimated ultrasound beam, applied through a probe 6mm in diameter with an input frequency of 3.0 MHz, an output intensity of 2.0 W/cm(2) (spatial average temporary peak; SATP), a pulse duty ratio of 50%, and a duration of 1 min. Sonoporation increased skin temperature from 26.8 °C to 27.3 °C, but there were no adverse effect such as burns. The mean level of TNF-α expression in siTNF-treated knee joints was 55% of those in controls. Delivery of siTNF into the knee joints every 3 days (i.e., 7, 10, 13, and 16 days after immunization) by in vivo sonoporation significantly reduced paw swelling on days 20-23 after immunization. Radiographic scores in the siTNF group were 56% of those in the CIA group and 61% of those in the siNeg group. Histological examination showed that the number of TNF-α positive cells was significantly lower in areas of pannus invasion into the ankle joints of siTNF- than of siNeg-treated rats. These results indicate that transduction of siTNF into articular synovium using sonoporation may be an effective local therapy for arthritis. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

A Synoviocyte Model for Osteoarthritis and Rheumatoid Arthritis: Response to Ibuprofen, Betamethasone, and Ginger Extract—A Cross-Sectional In Vitro Study

Directory of Open Access Journals (Sweden)

Søren Ribel-Madsen

2012-01-01

Full Text Available This study aimed at determining if synovial cell cultures from rheumatoid arthritis (RA, osteoarthritis (OA, and healthy controls (HC differ and are suitable disease models in pharmacological studies, and tested their response to some anti-inflammatory drugs. Synovial cells were isolated from synovial membrane or joint fluid. Cells were cultivated and exposed to no or TNF-α stimulation without, or in the presence of, betamethasone, ibuprofen, or a standardized ginger extract. Concentrations of a panel of cytokines, growth factors, and chemokines were mapped for each culture and condition. Our cells secreted an increased amount of the cytokines IL-1β, IL-6, and IL-8 in response to TNF-α stimulation in all conditions. OA cells showed a higher IL-6 and IL-8 and a lower IL-1β production, when not stimulated, than RA and HC cells, which were similar. TNF-α stimulation caused similar IL-1β, IL-6, and IL-8 release in all groups. Ibuprofen showed no effect on cytokine production, while ginger extract was similar to betamethasone. Ginger extract was as effective an anti-inflammatory agent as betamethasone in this in vitro model. Cultured fibroblast-like synoviocytes from OA and RA subjects promise to be a useful pharmacological disease model, but further studies, to support results from such a model are needed.

Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target

Directory of Open Access Journals (Sweden)

Mingxia Wang

2014-01-01

Full Text Available Sonic hedgehog (Shh signaling controls many aspects of human development, regulates cell growth and differentiation in adult tissues, and is activated in a number of malignancies. Rheumatoid arthritis (RA is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS. We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1 in RA synovial tissues was examined by immunohistochemistry (IHC and in FLS by IHC, immunofluorescence (IF, quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (P<0.05. Cyclopamine (a specific inhibitor of Shh signaling decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G1 phase. Our data show that Shh signaling is activated in synovium of RA patients in vivo and in cultured FLS form RA patients in vitro, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA.

Analysis of synovial fluid components of hydrarthrosis in long-term hemodialysis patients.

Science.gov (United States)

Shiota, E; Maekawa, M; Ohtani, M

1999-01-01

The synovial fluid components in long-term hemodialysis patients (HD; 43 knees in 43 patients) were investigated and compared with those in patients with osteoarthritis (OA; 21 knees in 21 patients) and rheumatoid arthritis (RA; 26 knees in 26 patients). The average ages in the three groups were, respectively, 60.7 years (range, 34-79 years), 63.2 years (range, 48-88 years), and 59.7 years (range, 37-76 years). The duration of hemodialysis in the HD group averaged 14.0 years (range, 4-24 years). The concentrations of hyaluronic acid, protein, and isomers of chondroitin sulfate (chondroitin 6-sulfate [C6S] and chondroitin 4-sulfate [C4S]) in the synovial fluid, and its viscosity were measured. Differences in each of the parameters were investigated according to disease clinical stage, roentgenological grade, and periods of dialysis in the HD group. The viscosity of the synovial fluid and the concentration of hyaluronic acid in HD patients were similar to those in OA patients; however, the C6S/C4S ratio in the synovial fluid of HD patients was similar to that in RA patients. The latter finding suggests that synovitis may be present in the hydrarthrosis of HD patients. The cause of this synovitis in HD patients remains to be elucidated.

Familial Mediterranean fever mimicking septic arthritis: distinguishing with diffusion weighted imaging

International Nuclear Information System (INIS)

Oner, Ali Yusuf; Ucar, Murat; Akpek, Sergin; Tokgoz, Nil

2007-01-01

FMF arthritis is generally monoarticular in origin. The affected joint is hot, tender, red and mimics septic arthritis. Conventional imaging findings, including magnetic resonance imaging (MRI) and ultrasound, do not help differentiate between these two entities. The final diagnosis depends on culture of the synovial fluid, and therefore initiation of proper drug therapy can be delayed. Diffusion weighted imaging (DWI), with its ability to detect altered water-proton mobility, might play an important role as a fast and non-invasive problem-solving tool in this setting. We here present MRI and DWI findings of a case of FMF arthritis mimicking septic arthritis. (orig.)

Analysis of the levels of endotoxin and β-d-glucan in the synovial fluid of hemodialysis patients.

Science.gov (United States)

Shiota, E; Maekawa, M; Kono, T

2001-12-01

Abstract We analyzed the levels of endotoxin and β-d-glucan, which possibly induce cytokine production, in the synovial fluid of patients on long-term hemodialysis and compared the results to those in patients with osteoarthritis and rheumatoid arthritis. We studied 42 knees in 42 hemodialysis patients, 21 in 21 osteoarthritis patients, and 26 in 26 rheumatoid arthritis patients. The mean ages were 60.7, 63.2, and 59.7 years, respectively. The duration of hemodialysis in the long-term hemodialysis group averaged 14.0 years. The concentrations of endotoxin and β-d-glucan in the synovial fluid of these three groups were measured. The concentration of endotoxin was the same in the three groups. However, the concentration of β-d-glucan was significantly higher in long-term hemodialysis patients. This finding suggests that β-d-glucan may have some relation to the pathogenesis of the synovitis which exists in the hydrarthrosis of long-term hemodialysis patients.

Wrist and finger joint MR imaging in rheumatoid arthritis

DEFF Research Database (Denmark)

Klarlund, Mette; Østergaard, Mikkel; Gideon, P

1999-01-01

PURPOSE: To elaborate the best MR imaging protocol for studies in rheumatoid arthritis (RA) and to evaluate the sensitivity and interobserver agreement with respect to detection of bone erosions (MR and radiography) and grading of synovial membrane hypertrophy (MR imaging only). MATERIAL...

The roles of MR imaging in monitoring therapeutic effectiveness in rheumatoid arthritis: preliminary result

Energy Technology Data Exchange (ETDEWEB)

Yun, Mi Jin; Suh, Jin Suck; Lee, Soo Kon; Lee, Ji Soo [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of); Cho, Jae Hyun [Ajou Univ. College of Medicine, Asan (Korea, Republic of)

1996-07-01

It is difficult to determine objectively therapeutic response in rheumatoid arthritis. This study was carried out in order to assess the feasibility of MR imaging to determine disease status following antirheumatoid medication. Eight patients with rheumatoid arthritis underwent MR studies before treatment and approximately one year after the beginning of antirheumatoid medication. Coronal images were obtained, using a T1- and T2-weighted spin echo(n=8), contrast-enhanced T1-weighted image(n=8) and dynamic contrast-enhanced image(n=4). Bone erosions, synovial hypertrophy and bone marrow enhancement in pre-and post-medication studies were compared. On dynamic study, enhancement ratio(E) of pannus was measured(E=SNR at 30sec/ SNR at precontrast). Changes of MRI findings and enhancement ratio between pre- and post-medication were compared with disease status as assessed by clinical index. In three patients, improvement of bone marrow edema and synovial hypertrophy was noted, and in addition, there was no evidence of newly developed bone erosion. In two of these patients, complete remission was noted on the basis of the ARA criteria. In another three patients, despite improvement of bone marrow edema and synovial hypertrophy and improved clinical parameters including morning stiffness and ESR, discrete and newly developed bone erosions were noted. In one patient with a poor response to antirheumatoid medication, aggravation of bone marrow edema and synovial hypertrophy was seen, but no definite change in bone erosions was noted. In the remaining one patient, no remarkable changes were seen in bone marrow edema, synovial hypertrophy or bone erosion. Clinically this patient showed no morning stiffness or elevated ESR. The enhancement ratio of pannus decreased in all 4 cases, especially where there were complete remission. Synovial extent, bone marrow enhancement, bone erosions and enhancement ratio of pannus may be good parameters for monitoring disease activity in the

The roles of MR imaging in monitoring therapeutic effectiveness in rheumatoid arthritis: preliminary result

International Nuclear Information System (INIS)

Yun, Mi Jin; Suh, Jin Suck; Lee, Soo Kon; Lee, Ji Soo; Cho, Jae Hyun

1996-01-01

It is difficult to determine objectively therapeutic response in rheumatoid arthritis. This study was carried out in order to assess the feasibility of MR imaging to determine disease status following antirheumatoid medication. Eight patients with rheumatoid arthritis underwent MR studies before treatment and approximately one year after the beginning of antirheumatoid medication. Coronal images were obtained, using a T1- and T2-weighted spin echo(n=8), contrast-enhanced T1-weighted image(n=8) and dynamic contrast-enhanced image(n=4). Bone erosions, synovial hypertrophy and bone marrow enhancement in pre-and post-medication studies were compared. On dynamic study, enhancement ratio(E) of pannus was measured(E=SNR at 30sec/ SNR at precontrast). Changes of MRI findings and enhancement ratio between pre- and post-medication were compared with disease status as assessed by clinical index. In three patients, improvement of bone marrow edema and synovial hypertrophy was noted, and in addition, there was no evidence of newly developed bone erosion. In two of these patients, complete remission was noted on the basis of the ARA criteria. In another three patients, despite improvement of bone marrow edema and synovial hypertrophy and improved clinical parameters including morning stiffness and ESR, discrete and newly developed bone erosions were noted. In one patient with a poor response to antirheumatoid medication, aggravation of bone marrow edema and synovial hypertrophy was seen, but no definite change in bone erosions was noted. In the remaining one patient, no remarkable changes were seen in bone marrow edema, synovial hypertrophy or bone erosion. Clinically this patient showed no morning stiffness or elevated ESR. The enhancement ratio of pannus decreased in all 4 cases, especially where there were complete remission. Synovial extent, bone marrow enhancement, bone erosions and enhancement ratio of pannus may be good parameters for monitoring disease activity in the

Synovial fluid analysis

Science.gov (United States)

Joint fluid analysis; Joint fluid aspiration ... El-Gabalawy HS. Synovial fluid analysis, synovial biopsy, and synovial pathology. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR, eds. Kelly's Textbook of ...

Inhibition of furin results in increased growth, invasiveness and cytokine production of synoviocytes from patients with rheumatoid arthritis.

Science.gov (United States)

Wu, Changshun; Song, Zezhong; Liu, Huiling; Pan, Jihong; Jiang, Huiyu; Liu, Chao; Yan, Zexing; Feng, Hong; Sun, Shui

2017-07-01

Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis play a key role by local production of cytokines and proteolytic enzymes that degrade the extracellular matrix and cartilage. These synoviocytes acquire phenotypic characteristics commonly observed in transformed cells, like anchorage-independent growth, increased proliferation and invasiveness, and insensitivity to apoptosis. Furin is a ubiquitous proprotein convertase that is capable of cleaving precursors of a wide variety of proteins. In patients with rheumatoid arthritis, furin is reported to be highly expressed in the synovial pannus compared with healthy persons. However, the mechanisms are poorly understood. This study is to explore the effect of furin overexpression in rheumatoid synoviocytes. In this study, RNA interference was used to knock down furin expression and to assess the resultant effects on biological behaviors of synoviocytes, such as cell proliferation, invasion, migration, cell cycle and cell apoptosis. In addition, the production of inflammatory cytokines was evaluated. The results showed that the inhibition of furin enhanced proliferation, invasion, and migration of synoviocytes in vitro. Cell cycle was accelerated and cell death was affected by furin knockdown. Also, the inhibition of furin increased interleukin-1β and tumor necrosis factor-α secretion of synoviocytes. Inhibition of furin enhances invasive phenotype of synoviocytes from patients with rheumatoid arthritis, implying a protective role of furin. Agents targeting upregulation of furin may have therapeutic potential for rheumatoid arthritis. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

/sup 133/Xe clearance of the knee joint of patients suffering from arthritis and osteoarthrosis

Energy Technology Data Exchange (ETDEWEB)

Balint, G.; Reviczky, L.A.; Lendvay, J.; Boehm, U.; Kucsera, K.; Genti, Gy. (Orszagos Reuma es Fizioterapias Intezet, Budapest (Hungary))

1982-01-01

65 inflammed and 13 non-inflammed knee joints of patients suffering from osteoarthrosis were examined by the Xe/sup 133/ clearance method. The control group consisted of 27 patients with exsudative arthritis of the knee. The counts of 80 ..mu..C /sup 133/Xe given intraarticcularly were measured above the knee joint by NK 350 energy selective counter. The time needed to halve the count rate measured in the 4th minute after administration (biological half life (T1/2)) was significantly different in the three groups. It was the longest in the non-inflammed arthrosis, the shortest in the exsudative arthritis group. Significant differences were apparent regarding joint pain and tenderness in all the three groups. Though the synovial protein level and the C/sub 3/ complement level were significantly different, in the three groups no relationship was found between the T1/2 and synovial/serum protein ratio or between the synovial/serum C/sub 3/ ratio. The authors concluded that /sup 133/Xe clearance, which measures the perfusion of the synovial membrane, can be used for measuring the inflammatory activity of knee joint synovitis.

RAGE and activation of chondrocytes and fibroblast-like synoviocytes in joint diseases

NARCIS (Netherlands)

Steenvoorden, Marjan Maria Claziena

2007-01-01

This dissertation describes a new model in which cartilage degradation can be studied. New cartilage is formed by bovine chondrocytes obtained from the slaughterhouse and cocultured with synovial cells from rheumatoid arthritis (RA) patients to study the interaction between the chondrocytes and

Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.

Science.gov (United States)

Ota, Yuri; Niiro, Hiroaki; Ota, Shun-Ichiro; Ueki, Naoko; Tsuzuki, Hirofumi; Nakayama, Tsuyoshi; Mishima, Koji; Higashioka, Kazuhiko; Jabbarzadeh-Tabrizi, Siamak; Mitoma, Hiroki; Akahoshi, Mitsuteru; Arinobu, Yojiro; Kukita, Akiko; Yamada, Hisakata; Tsukamoto, Hiroshi; Akashi, Koichi

2016-03-16

The efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation. Peripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells. RANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro. Our current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.

MR imaging of arthropathies of juvenile arthritis and hemophilia

International Nuclear Information System (INIS)

Yulish, B.S.; Lieberman, J.; Mulopoulos, G.P.; Strandjord, S.; Newman, A.; Goodfellow, D.; Bryan, P.J.; Modic, M.T.

1986-01-01

The arthropathies of juvenile arthritis and hemophilia have in common abnormal hyperplastic synovium leading to marginal bone erosion, articular cartilage destruction, subchondral bone exposure, and dissolution and ultimately collapse of the affected joint. The authors examined children and young adults with juvenile arthritis and hemophilia by MR imaging and found that they could identify hyperplastic synovium, articular cartilage lesions, bone erosions, and joint effusions. This has therapeutic implications since identification of progressive synovial hyperplasia and/or early cartilage or marginal bone erosion may lead to earlier synovectomy in patients with hemophilia or switch to second line drugs in patients with juvenile arthritis, in an attempt to prevent progressive joint destruction

Readout-segmented multi-shot diffusion-weighted MRI of the knee joint in patients with juvenile idiopathic arthritis.

Science.gov (United States)

Sauer, Alexander; Li, Mengxia; Holl-Wieden, Annette; Pabst, Thomas; Neubauer, Henning

2017-10-12

Diffusion-weighted MRI has been proposed as a new technique for imaging synovitis without intravenous contrast application. We investigated diagnostic utility of multi-shot readout-segmented diffusion-weighted MRI (multi-shot DWI) for synovial imaging of the knee joint in patients with juvenile idiopathic arthritis (JIA). Thirty-two consecutive patients with confirmed or suspected JIA (21 girls, median age 13 years) underwent routine 1.5 T MRI with contrast-enhanced T1w imaging (contrast-enhanced MRI) and with multi-shot DWI (RESOLVE, b-values 0-50 and 800 s/mm 2 ). Contrast-enhanced MRI, representing the diagnostic standard, and diffusion-weighted images at b = 800 s/mm 2 were separately rated by three independent blinded readers at different levels of expertise for the presence and the degree of synovitis on a modified 5-item Likert scale along with the level of subjective diagnostic confidence. Fourteen (44%) patients had active synovitis and joint effusion, nine (28%) patients showed mild synovial enhancement not qualifying for arthritis and another nine (28%) patients had no synovial signal alterations on contrast-enhanced imaging. Ratings by the 1st reader on contrast-enhanced MRI and on DWI showed substantial agreement (κ = 0.74). Inter-observer-agreement was high for diagnosing, or ruling out, active arthritis of the knee joint on contrast-enhanced MRI and on DWI, showing full agreement between 1st and 2nd reader and disagreement in one case (3%) between 1st and 3rd reader. In contrast, ratings in cases of absent vs. little synovial inflammation were markedly inconsistent on DWI. Diagnostic confidence was lower on DWI, compared to contrast-enhanced imaging. Multi-shot DWI of the knee joint is feasible in routine imaging and reliably diagnoses, or rules out, active arthritis of the knee joint in paediatric patients without the need of gadolinium-based i.v. contrast injection. Possibly due to "T2w shine-through" artifacts, DWI does not reliably

15-hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes.

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Kim, Hak-Jae; Lee, Sora; Lee, Haw-Yong; Won, Hansol; Chang, Sung-Hae; Nah, Seong-Su

2015-09-01

15-Hydroxyprostaglandin dehydrogenase (HPGD) is the key enzyme responsible for the metabolic inactivation of prostaglandin E2 (PGE2) catabolism. PGE2 is one of the predominant catabolic factors involved in rheumatoid arthritis (RA). However, the expression and regulation of HPGD in RA fibroblast‑like synoviocyte (FLS) remain to be elucidated. Disease‑modifying anti‑rheumatic drugs (DMARDs) are the most important anti‑arthritic drugs, which reduce the effect of joint injury. The aim of the present study was to assess the expression of HPGD in RA tissues and cells, and normal synovial tissues and cells. The effect of the most popular DMARDs, hydroxychloroquine, on the expression of HPGD in RA‑FLS was also investigated. Western blotting and immunohistochemical analysis demonstrated that the expression levels of HPGD in human synovium were lower in RA synovium compared with the normal and OA synovium. In RA‑FLS, the expression of HPGD was increased following treatment with several DMARDs, including sulfasalazine, methotrexate, and hydroxychloroquine. Hydroxychloroquine (10 µM) treatment induced the phosphorylation of ERK, SAPK/JNK and p38. Hydroxychloroquine induced a decrease in the release of PGE2, which was restored by mitogen‑activated protein (MAP) kinase pathway inhibitors. Hydroxychloroquine may therefore, affect the pathogenesis of RA through the MAP kinase pathway by regulating the expression of HPGD.

MRI findings of the knee in rheumatoid arthritis

International Nuclear Information System (INIS)

Kanno, Hiromasa; Yuasa, Shoichi; Choukan, Toshinori; Oonuma, Shinichi; Matsunaga, Toshiki

1996-01-01

The studies were done to know in what extent MRI can image the pannus invasion and cysts in the subcartilagious tissues which are not revealed by the scout roentgenogram and how the synovial membrane can be enhanced by gadolinium-DTPA (Gd-DTPA). Twenty five knees in rheumatoid arthritis of 21 patients, mean age of 57.8 years, were subjected to the studies. Thirteen knees were in Larsen grade 0, 3 in grade I, 4 in grade II, 2 in grade III and 3 in grade IV, whose osteolytic degree were small. MRI system was 0.5 Tesla superconducting Toshiba MRT50A. Imaging was performed by the field echo method with 4 mm-thick slice of T1, T2 weighted images of sagittal and frontal sections, and 5 min after intravenous injection of Gd-DTPA, of T1 weighted images of frontal and sagittal sections. Subcartilagious cysts not detectable on the scout roentgenogram were found in 13 knees (52%) on the MRI image. MRI after Gd-DTPA gave the enhanced images of surroundings of joint capsule in 15 cases, of dotted or reticular synovial membrane in 2 and of joint capsule surroundings with dotted membrane in 2. One case showed no enhancement. MRI was thus found useful for detection of cysts and pannus in the early knee rheumatoid arthritis with insignificant osteolysis. MRI after Gd-DTPA enhanced the surroundings of joint capsule in most cases, and in some cases, the synovial membrane in a dotted or reticular manner, which was considered to show the dilated blood vessels or necrotic coagulations of synovial villi. (H.O.)

MRI findings of the knee in rheumatoid arthritis

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Kanno, Hiromasa; Yuasa, Shoichi; Choukan, Toshinori; Oonuma, Shinichi; Matsunaga, Toshiki [Jusendo General Hospital, Koriyama, Fukushima (Japan)

1996-03-01

The studies were done to know in what extent MRI can image the pannus invasion and cysts in the subcartilagious tissues which are not revealed by the scout roentgenogram and how the synovial membrane can be enhanced by gadolinium-DTPA (Gd-DTPA). Twenty five knees in rheumatoid arthritis of 21 patients, mean age of 57.8 years, were subjected to the studies. Thirteen knees were in Larsen grade 0, 3 in grade I, 4 in grade II, 2 in grade III and 3 in grade IV, whose osteolytic degree were small. MRI system was 0.5 Tesla superconducting Toshiba MRT50A. Imaging was performed by the field echo method with 4 mm-thick slice of T1, T2 weighted images of sagittal and frontal sections, and 5 min after intravenous injection of Gd-DTPA, of T1 weighted images of frontal and sagittal sections. Subcartilagious cysts not detectable on the scout roentgenogram were found in 13 knees (52%) on the MRI image. MRI after Gd-DTPA gave the enhanced images of surroundings of joint capsule in 15 cases, of dotted or reticular synovial membrane in 2 and of joint capsule surroundings with dotted membrane in 2. One case showed no enhancement. MRI was thus found useful for detection of cysts and pannus in the early knee rheumatoid arthritis with insignificant osteolysis. MRI after Gd-DTPA enhanced the surroundings of joint capsule in most cases, and in some cases, the synovial membrane in a dotted or reticular manner, which was considered to show the dilated blood vessels or necrotic coagulations of synovial villi. (H.O.)

Acral synovial chondrosarcoma

International Nuclear Information System (INIS)

Wenger, D.E.; Sundaram, M.; Unni, K.K.; Janney, C.G.; Merkel, K.

2002-01-01

Acral chondrosarcoma is rare. Synovial chondrosarcoma is even rarer. Synovial chondrosarcoma arising without evidence of pre-existing or concurrent synovial chondromatosis is exceedingly rare. We present a case of acral synovial chondrosarcoma involving both sides of the metacarpophalangeal joint of the thumb in a 69-year-old man. Radiographically, the lesion mimicked gout. On MR imaging, the lobulated contours of the soft tissue mass suggested synovial chondromatosis. Histological examination revealed a chondrosarcoma, which on the basis of imaging findings we present as having arisen from the synovium. The tumor invaded a portion of the cartilage of the metacarpophalangeal joint and equally destroyed the bones of the distal metacarpal and base of the proximal phalanx of the thumb, while sparing the bony joint surfaces. (orig.)

Exposure to Candida albicans polarizes a T-cell driven arthritis model towards Th17 responses, resulting in a more destructive arthritis.

Science.gov (United States)

Marijnissen, Renoud J; Koenders, Marije I; van de Veerdonk, Frank L; Dulos, John; Netea, Mihai G; Boots, Annemieke M H; Joosten, Leo A B; van den Berg, Wim B

2012-01-01

Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis. Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of C. albicans or Zymosan A. During the chronic phase of the arthritis, the cytokine levels, mRNA expression and histopathological analysis of the joints were performed. To investigate the phenotype of the IL-17 producing T-cells, synovial cells were isolated and analyzed by flowcytometry. Intra-articular injection of either Zymosan A or C. albicans on top of the SCW injection both resulted in enhanced joint swelling and inflammation compared to the normal SCW group. However, only the addition of C. albicans during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to C. albicans led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and RORγT. Moreover, the C. albicans-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-γ. This study clearly shows that minute amounts of fungal components, like C. albicans, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype.

Bone pathology inpsoriatic arthritis

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V. V. Badokin

2007-01-01

Full Text Available Objective. To study different variants of osteolysis in pts with psoriatic arthritis (PA and to reveal their relationship with other clinico-radiological features of joint damage. Material and methods. 370 pts with definite PA having different variants of joint damage were included. Radiological examination of bones and joints (in some cases large picture frame was performed. Morphological evaluation of synovial biopsies was done in 34 pts with PA and 10 pts with rheumatoid arthritis (RA. Results. Different types of osteolysis were revealed in 80 (21,6% pts. Osteolytic variant of joint damage was present in 29 pts. 33 pts had acral, 48 — intra-articular osteolysis and 16 - true bone atrophy. Frequency and intensity of bone resorption were associated with severity of PA. Acral osteolysis correlated with arthritis of distal interphalangeal joints and onychodystrophy. Intra-articular osteolysis was most often present in distal interphalangeal joints of hands and metacarpophalangeal joints (39,6% and 41,7% respectively. Characteristic feature of PA was combination of prominent resorption with formation of bone ankylosis and periosteal reaction. Ankylosis was present in 33,3% of pts with intra-articular osteolysis and in 60% of pts with combination of different osteolysis variants. Systemic reaction of microcirculation in synovial biopsies was most prominent in osteolytic variant: marked thickening of capillary and venule basal membrane with high level of acid phosphatase, increased capillary and precapillary blood flow with stasis features, vascular lymphocyte and macrophage infiltration, productive vasculitis with annular wall thickening, thrombovasculitis and villi deep layer sclerosis. Conclusion. Different variants of osteolysis show bone involvement in PA. Acral and intra- articular osteolysis association with bone ankylosis and periostitis proves their common pathogenetic entity.

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular point. Part I: histological effects

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Nyengaard Jens R

2009-02-01

Full Text Available Abstract Background Temporomandibular joint (TMJ arthritis in children causes alterations in craniomandibular growth. This abnormal growth may be prevented by an early anti-inflammatory intervention. We have previously shown that intra-articular (IA corticosteroid reduces TMJ inflammation, but causes concurrent mandibular growth inhibition in young rabbits. Blockage of TNF-α has already proven its efficacy in children with juvenile idiopathic arthritis not responding to standard therapy. In this paper we evaluate the effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in rabbits on histological changes using histomorphometry and stereology. This article presents the data and discussion on the anti-inflammatory effects of systemic and IA etanercept. In Part II the data on the effects of systemic and IA etanercept on facial growth are presented. Methods Forty-two rabbits (10 weeks old pre-sensitized with ovalbumin and locally induced inflammation in the temporomandibular joints were divided into three groups: a placebo group receiving IA saline injections in both joints one week after arthritis induction (n = 14, an IA etanercept group receiving 0.1 mg/kg etanercept per joint one week after arthritis induction (n = 14 and a systemic etanercept group receiving 0.8 mg/kg etanercept weekly throughout the 12-week study (n = 14. Arthritis was maintained by giving four inductions three weeks apart. Additional IA saline or etanercept injections were also given one week after the re-inductions. Histomorphometric and unbiased stereological methods (optical fractionator were used to assess and estimate the inflammation in the joints. Results The histomorphometry showed synovial proliferation in all groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating with systemic etanercept but not with IA etanercept. Semi-quantitative assessments of synovial proliferation and

Arthritis severity locus Cia4 is an early regulator of IL-6, IL-1β, and NF-κB activators' expression in pristane-induced arthritis

OpenAIRE

Brenner, Max; Laragione, Teresina; Gulko, Pércio S.

2013-01-01

Cia4 is a locus on rat chromosome 7 that regulates disease severity and joint damage in models of rheumatoid arthritis, including pristane-induced arthritis (PIA). To identify molecular processes regulated by Cia4, synovial tissues from MHC-identical DA (severe erosive) and DA.F344(Cia4) congenics (mild nonerosive) rats were collected at preclinical and recent onset stages following the induction of PIA and analyzed for gene expression levels. Il6 levels were significantly higher in DA compar...

Synovial volume--a marker of disease severity in rheumatoid arthritis? Quantification by MRI

DEFF Research Database (Denmark)

Østergaard, Mikkel; Gideon, P; Henriksen, O

1994-01-01

Volumes of synovial membrane and joint effusion were determined by magnetic resonance imaging (MRI) in patients with inflammatory gonarthritis. Volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted...

Triggering of the dsRNA sensors TLR3, MDA5, and RIG-I induces CD55 expression in synovial fibroblasts.

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Olga N Karpus

Full Text Available CD55 (decay-accelerating factor is a complement-regulatory protein highly expressed on fibroblast-like synoviocytes (FLS. CD55 is also a ligand for CD97, an adhesion-type G protein-coupled receptor abundantly present on leukocytes. Little is known regarding the regulation of CD55 expression in FLS.FLS isolated from arthritis patients were stimulated with pro-inflammatory cytokines and Toll-like receptor (TLR ligands. Transfection with polyinosinic-polycytidylic acid (poly(I:C and 5'-triphosphate RNA were used to activate the cytoplasmic double-stranded (dsRNA sensors melanoma differentiation-associated gene 5 (MDA5 and retinoic acid-inducible gene-I (RIG-I. CD55 expression, cell viability, and binding of CD97-loaded beads were quantified by flow cytometry.CD55 was expressed at equal levels on FLS isolated from patients with rheumatoid arthritis (RA, osteoarthritis, psoriatic arthritis and spondyloarthritis. CD55 expression in RA FLS was significantly induced by IL-1β and especially by the TLR3 ligand poly(I:C. Activation of MDA5 and RIG-I also enhanced CD55 expression. Notably, activation of MDA5 dose-dependently induced cell death, while triggering of TLR3 or RIG-I had a minor effect on viability. Upregulation of CD55 enhanced the binding capacity of FLS to CD97-loaded beads, which could be blocked by antibodies against CD55.Activation of dsRNA sensors enhances the expression of CD55 in cultured FLS, which increases the binding to CD97. Our findings suggest that dsRNA promotes the interaction between FLS and CD97-expressing leukocytes.

Temporomandibular joint involvement in rheumatoid arthritis patients: association between clinical and tomographic data

OpenAIRE

Cordeiro, Patrícia C. F; Guimaraes, Josemar P; de Souza, Viviane A; Dias, Isabela M; Silva, Jesca N. N; Devito, Karina L; Bonato, Leticia L

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and synovial hyperplasia, which usually affects multiple joints. The temporomandibular joint (TMJ) becomes susceptible to the development of changes resulting from RA. The aim of this study was to evaluate the presence of TMD and degenerative bone changes in TMJ in patients diagnosed with RA (rheumatoid arthritis). The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/ TMD) questio...

Evidence-based diagnostics: adult septic arthritis.

Science.gov (United States)

Carpenter, Christopher R; Schuur, Jeremiah D; Everett, Worth W; Pines, Jesse M

2011-08-01

% to 38%). With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or skin infection overlying a prosthetic joint (+LR = 15.0), history, physical examination, and serum tests do not significantly alter posttest probability. Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely. The interval LR for synovial white blood cell (sWBC) counts of 0 × 10(9)-25 × 10(9)/L was 0.33; for 25 × 10(9)-50 × 10(9)/L, 1.06; for 50 × 10(9)-100 × 10(9)/L, 3.59; and exceeding 100 × 10(9)/L, infinity. Synovial lactate may be useful to rule in or rule out the diagnosis of septic arthritis with a +LR ranging from 2.4 to infinity, and negative likelihood ratio (-LR) ranging from 0 to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the causative organism within 3 hours. Based on 56% sensitivity and 90% specificity for sWBC counts of >50 × 10(9)/L in conjunction with best-evidence estimates for diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis test threshold is 5%, with a treatment threshold of 39%. Recent joint surgery or cellulitis overlying a prosthetic hip or knee were the only findings on history or physical examination that significantly alter the probability of nongonococcal septic arthritis. Extreme values of sWBC (>50 × 10(9)/L) can increase, but not decrease, the probability of septic arthritis. Future ED-based diagnostic trials are needed to evaluate the role of clinical gestalt and the efficacy of nontraditional synovial markers such as lactate. © 2011 by the Society for Academic Emergency Medicine.

Synovial volume--a marker of disease severity in rheumatoid arthritis? Quantification by MRI

DEFF Research Database (Denmark)

Østergaard, Mikkel; Gideon, P; Henriksen, O

1994-01-01

MR-images. Ten knees with clinically active gonarthritis (CAG), 8 knees with clinically inactive gonarthritis (CIG) and 5 healthy controls (HC) were examined. The synovial volume of CAG-, CIG- and HC-knees were significantly different. The median volumes were 79 ml, 21 ml and 3 ml, respectively...

The role of ultrasound in the diagnosis and follow-up of early inflammatory arthritis

International Nuclear Information System (INIS)

Spencer, S.P.; Ganeshalingam, S.; Kelly, S.; Ahmad, M.

2012-01-01

The inflammatory arthritides are a group of chronic, often debilitating disorders characterized by synovial inflammation and progressive joint destruction. The primary diagnostic aim is to recognize the inflammatory arthritis at an early stage, such that therapies may be implemented before irreversible joint destruction has occurred. The radiologist now plays a pivotal role both in making an accurate and early diagnosis of inflammatory arthritis as well as assessing treatment response. This article reviews the current literature and presents our approach to the sonographic assessment of early inflammatory arthritis.

The Synovial Lining and Synovial Fluid Properties after Joint Arthroplasty

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Michael Shang Kung

2015-05-01

Full Text Available The lubrication of the cartilaginous structures in human joints is provided by a fluid from a specialized layer of cells at the surface of a delicate tissue called the synovial lining. Little is known about the characteristics of the fluids produced after a joint arthroplasty procedure. A literature review was carried out to identify papers that characterized the synovial lining and the synovial fluids formed after total hip or knee arthroplasty. Five papers about synovial lining histology and six papers about the lubricating properties of the fluids were identified. The cells making up the re-formed synovial lining, as well as the lining of interface membranes, were similar to the typical Type A and B synoviocytes of normal joints. The synovial fluids around joint replacement devices were typically lower in viscosity than pre-arthroplasty fluids but the protein concentration and phospholipid concentrations tended to be comparable, suggesting that the lining tissue function was preserved after arthroplasty. The widespread, long-term success of joint arthroplasty suggests that the lubricant formed from implanted joint synovium is adequate for good clinical performance in the majority of joints. The role the fluid plays in component wear or failure is a topic for future study.

Tumour necrosis factor-α inhibitors are glucocorticoid-sparing in rheumatoid arthritis

DEFF Research Database (Denmark)

Nilsson, Anna Christine; Christensen, Anne Friesgaard; Junker, Peter

2011-01-01

Rheumatoid arthritis (RA) is a chronic disease with autoimmune traits of unknown aetiology which primarily affects synovial joints. Glucocorticoids (GCs) are still widely used in RA treatment despite the expanding use of targeted and very efficient agents. The objective of this study was to assess...

Interleukin-33 Receptor (ST2 Deficiency Improves the Outcome of Staphylococcus aureus-Induced Septic Arthritis

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Larissa Staurengo-Ferrari

2018-05-01

Full Text Available The ST2 receptor is a member of the Toll/IL-1R superfamily and interleukin-33 (IL-33 is its agonist. Recently, it has been demonstrated that IL-33/ST2 axis plays key roles in inflammation and immune mediated diseases. Here, we investigated the effect of ST2 deficiency in Staphylococcus aureus-induced septic arthritis physiopathology. Synovial fluid samples from septic arthritis and osteoarthritis individuals were assessed regarding IL-33 and soluble (s ST2 levels. The IL-33 levels in samples from synovial fluid were significantly increased, whereas no sST2 levels were detected in patients with septic arthritis when compared with osteoarthritis individuals. The intra-articular injection of 1 × 107 colony-forming unity/10 μl of S. aureus American Type Culture Collection 6538 in wild-type (WT mice induced IL-33 and sST2 production with a profile resembling the observation in the synovial fluid of septic arthritis patients. Data using WT, and ST2 deficient (−/− and interferon-γ (IFN-γ−/− mice showed that ST2 deficiency shifts the immune balance toward a type 1 immune response that contributes to eliminating the infection due to enhanced microbicide effect via NO production by neutrophils and macrophages. In fact, the treatment of ST2−/− bone marrow-derived macrophage cells with anti-IFN-γ abrogates the beneficial phenotype in the absence of ST2, which confirms that ST2 deficiency leads to IFN-γ expression and boosts the bacterial killing activity of macrophages against S. aureus. In agreement, WT cells achieved similar immune response to ST2 deficiency by IFN-γ treatment. The present results unveil a previously unrecognized beneficial effect of ST2 deficiency in S. aureus-induced septic arthritis.

MRI features of Lyme arthritis of the hips

International Nuclear Information System (INIS)

Amini, Behrang; Geller, Matthew D.; Mathew, Manesh; Gerard, Perry

2007-01-01

Diagnosing Lyme arthritis without a history of travel to endemic regions or erythema migrans can be a challenge. Radiographic and ultrasonographic findings are nonspecific for the diagnosis of Lyme arthritis. We present the MRI features of Lyme disease of the hip in a 4-year-old boy who presented with hip pain and was found to have Lyme disease by Western blot. Our findings include bilateral hip effusions and synovial enhancement, normal bone marrow signal intensity without enhancement, minimal adjacent muscular and soft-tissue edema, and bilateral inguinal lymph nodes measuring up to 1 cm. (orig.)

MRI features of Lyme arthritis of the hips

Energy Technology Data Exchange (ETDEWEB)

Amini, Behrang [Maimonides Medical Center, Department of Surgery, Brooklyn, NY (United States); Geller, Matthew D. [New York College of Osteopathic Medicine, Old Westbury, NY (United States); Mathew, Manesh; Gerard, Perry [Maimonides Medical Center, Department of Radiology, Brooklyn, NY (United States)

2007-11-15

Diagnosing Lyme arthritis without a history of travel to endemic regions or erythema migrans can be a challenge. Radiographic and ultrasonographic findings are nonspecific for the diagnosis of Lyme arthritis. We present the MRI features of Lyme disease of the hip in a 4-year-old boy who presented with hip pain and was found to have Lyme disease by Western blot. Our findings include bilateral hip effusions and synovial enhancement, normal bone marrow signal intensity without enhancement, minimal adjacent muscular and soft-tissue edema, and bilateral inguinal lymph nodes measuring up to 1 cm. (orig.)

Septic arthritis: a 12 years retrospective study in a rheumatological university clinic

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L. Riato

2011-09-01

Full Text Available Background: Septic arthritis is a disabling and potentially life-threatening condition that requires prompt diagnosis and treatment. The most important risk factors are joint prosthesis, pre-existing joint disease and immunosuppressive drugs. The aim of our study therefore was to revaluate all septic arthritis cases discharged from our Rheumatologic Unit in the last 12 years, to assess the risk factors, the clinical and laboratory characteristics, the causative microorganisms and its possible increase in frequency. Methods: The medical records of 42 consecutive patients with septic arthritis discharged from our Rheumatology Unit between January 1995 and December 2006 were reviewed. The patients ranged in age from 23 to 90 and there isn’t gender predominance. Septic arthritis was diagnosed based on the finding of purulent material in the joint space and/or the isolation of a bacterial pathogen from joint fluid. Demographic data, risk factors, co-morbidity, clinical manifestations, time interval between symptoms onset and diagnosis, treatment and laboratory data including serum white blood cell count, erythrocyte sedimentation rate (ESR, C reactive protein (CRP, synovial white blood cells and culture results were analysed. We considered these parameters in the whole population and in two different age groups (≤60, >60 and tried to determine if there was a change of microorganisms involved in septic arthritis during the years. Results: Of 42 patients, 47% were aged 60 and younger. Only 10 patients were admitted to our unit before 2001. A predisposing factor was recorded in 90,5% of cases: 15 patients had rheumatoid arthritis, 8 were diabetic, 6 had seronegative arthritis, 4 had a connective tissue disease, 8 patients had a prosthetic infection and 3 were subjected recently to arthrocentesis. We found that patients aged 60 and younger were more frequently affected by joint disease and had a synovial white blood cell count lower than patients

Rheumatoid arthritis of the wrist; Dynamic Gd-DTPA enhanced MRT. Rheumatoide Arthritis des Handgelenkes; Dynamische Gd-DTPA-verstaerkte MRT

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Naegele, M. (Radiologische Universitaetsklinik, Bonn (Germany)); Kunze, V. (Radiologische Universitaetsklinik, Bonn (Germany)); Koch, W. (Orthopaedische Universitaetsklinik, Bonn (Germany)); Bruening, R. (Radiologische Universitaetsklinik, Bonn (Germany)); Seelos, K. (Radiologische Universitaetsklinik, Bonn (Germany)); Stroehmann, I. (Radiologische Universitaetsklinik, Bonn (Germany)); Woell, B. (Radiologische Universitaetsklinik, Bonn (Germany)); Reiser, M. (Radiologische Universitaetsklinik, Bonn (Germany))

1993-02-01

21 patients with rheumatoid arthritis of the wrist diagnosed according to the criteria of the American Rheumatism Association were examined by dynamic MRT before and after the i.v. injection of Gd-DTPA (0.1 mmol/kg). The results were correlated with the clinical and radiological findings. The increased signal intensity of the pannus was 1.17[+-]0.45%/sec and this differed significantly (p<0.001) from bone marrow (0.16[+-]0.11%/sec) and from muscle (0.25[+-]0.16%/sec). Blood sedimentation rate correlated with the gradient of synovial proliferation (p<0.05). There were no further statistically significant correlations between the clinical, radiological and MRT findings and the change in signal intensity from synovial proliferation as shown by dynamic MRT. (orig.)

Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals.

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Karen I Maijer

Full Text Available We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA.Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF and/or anti-citrullinated protein antibodies (ACPA, without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27. Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry.The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2; p = 0.020, also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5; p = 0.016. This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529 and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520 and ESR (leptin r = 0.512, chemerin r = 0.708, p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis.In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals.

Radiographic manifestations of arthritis in AIDS patients

International Nuclear Information System (INIS)

Rosenberg, Z.S.; Norman, A.; Solomon, G.

1988-01-01

The purpose of this study is to familiarize the radiologist with a newly discovered association between arthritis and acquired immunodeficiency syndrome (AIDS). The authors retrospectively reviewed the clinical and radiographic findings in 31 patients with human immunodeficiency virus (HIV) infection referred to their rheumatology clinic with musculoskeletal complaints. The patients carried a wide range of clinical diagnosis including Reiter syndrome, psoriatic arthritis, undifferentiated seronegative arthritis, isolated enthesopathies, rheumatoid arthritis and osteonecrosis. Radiographs were available in 24 of the 31 patients, and in 20 they showed radiographic features of arthritis, which included soft-tissue swelling periarticular osteoporosis, synovial effusions, sacroiliitis, periosteal reaction, joint space narrowing, marginal erosions, and osteonecrosis. Although the radiographic abnormalities were frequently mild, they were significant, given the short duration of disease in many of their patients (weeks to months) at the time radiographs were obtained. The range of radiographic findings in their series was varied and paralleled the wide range of clinical diagnoses. No findings were pathognomonic for HIV-associated arthritis. Nevertheless, HIV infection needs to be considered in any patient belonging to a recognized risk group who presents with musculoskeletal disease. This is particularly important since immunosupressive drugs used for the treatment of arthritis can be detrimental to patients with HIV infection

Synovial and inflammatory diseases in childhood: role of new imaging modalities in the assessment of patients with juvenile idiopathic arthritis

International Nuclear Information System (INIS)

Damasio, Maria Beatrice; Malattia, Clara; Martini, Alberto; Toma, Paolo

2010-01-01

Juvenile idiopathic arthritis (JIA) represents a group of heterogeneous diseases characterized by a chronic inflammatory process primarily targeting the synovial membrane. A persistent synovitis is associated with an increased risk of osteocartilaginous damage. With the advent of effective structure-modifying treatment for JIA, it may be possible to significantly reduce or even completely prevent structural damage and associated functional disability. The trend towards early suppression of inflammation, in order to prevent erosive disease, shifts the emphasis away from conventional radiographic detectable structural damage to the slightest traces of early joint damage, and drives the need for alternative imaging techniques more sensitive in detecting early signs of disease activity and damage. In this regard MRI and US are playing an increasing role in the evaluation of arthritic joints. This article will review the key aspects of the current status and recent important advances of imaging techniques available to investigate the child with rheumatic disease, briefly discussing conventional radiography, and particularly focusing on MRI and US. In this era of advancing imaging technology, knowledge of the relative values of available imaging techniques is necessary to optimize the management of children with JIA. (orig.)

Quantitative magnetic resonance imaging as marker of synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy: a one year follow up study

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Østergaard, Mikkel; Ejbjerg, B; Stoltenberg, M

2001-01-01

OBJECTIVES: By repeated magnetic resonance imaging (MRI) to study synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) and other (non-RA) causes of persistent knee joint synovitis. METHODS: Contrast enhanced...... at two months. No significant differences between volumes in RA and non-RA knees were seen. Synovial membrane volumes at two months were significantly inversely correlated with the duration of clinical remission, for all knees considered together (Spearman's correlation r(s)=-0.67; p

LEVELS OF ANGIOGENESIS-REGULATORY CHEMOKINES IN THE SYNOVIAL FLUID OF PATIENTS WITH RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

D. A. Zhebrun

2015-01-01

Full Text Available The role of chemokines in the immunopathogenesis of rheumatoid arthritis (RA has been actively investigated in recent years. Angiogenic and angiostatic chemokines are important mediators of angiogenesis in the development and extent of pannus. Peripheral blood and synovial fluid (SF is a major biomaterial in clinical and immunological studies. At the same time, it is the SF test that may yield the most informative results since that gives an idea of the processes that occur locally within a joint. Objective: to perform a comparative analysis of the levels of a number of CXC, CC, and CX3C chemokines in the SF of patients with RA, osteoarthritis (OA, and joint injuries. Subjects and methods. The multiplex analysis using xMAP technology (Luminex, USA was used to analyze levels of CXC, CC, and CX3C chemokines in SF and serum of patients with RA (n = 20, OA (n = 9 and controls (n = 9. Results and discussion. The SF levels of CCL24/eotaxin-2, as well as those of the angiostatic chemokines CXCL9/MIG, CXCL10/IP10, CXCL11/ITAC, and CXCL13/BCA-1 were higher in the RA group than in the control and OA groups. There was a direct correlation between SF levels of CCL5/RANTES and DAS28, as well as patient global disease activity assessment on visual analogue scale, and that between the level of CCL2/MCP-1 in the SF and that of anticyclic citrullinated peptide (anti-CCP antibodies in the serum. The SF concentrations of CXCL5/ENA78 and CXCL7/NAP-2 were shown to depend on the presence of serum anti-CCP. Serum CXCL13/BCA-1 levels were higher in RA than those in OA, as that of CXCL7/NAP-2 than in the control group.

Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology

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Axelsen, Mette Bjørndal; Stoltenberg, M.; Poggenborg, R.

2012-01-01

, the average grade of histological synovial inflammation was determined from four biopsies obtained during surgery. A preoperative series of T(1)-weighted dynamic fast low-angle shot (FLASH) MR images was obtained. Parameters characterizing contrast uptake dynamics, including the initial rate of enhancement...... capsule of the knee joint (Precise ROI). Intra- and interreader agreement was assessed using the intra-class correlation coefficient (ICC). Results: The IRE from the Quick ROI and the Precise ROI revealed high correlations to the grade of histological inflammation (Spearman's correlation coefficient (rho......) = 0.70, p = 0.001 and rho = 0.74, p = 0.001, respectively). Intraand inter-reader ICCs were very high (0.93-1.00). No Whole slice parameters were correlated to histology. Conclusion: DCE-MRI provides fast and accurate assessment of synovial inflammation in RA patients. Manual outlining of the joint...

The expression change of β-arrestins in fibroblast-like synoviocytes from rats with collagen-induced arthritis and the effect of total glucosides of paeony.

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Wang, Qing-Tong; Zhang, Ling-Ling; Wu, Hua-Xun; Wei, Wei

2011-01-27

To investigate the expression of β-arrestins in fibroblast-like synoviocytes (FLS) from collagen-induced arthritis (CIA) rats and the effect of total glucosides of paeony (TGP). TGP and glucosides of tripterygium wilfordii (GTW) were intragastriclly administrated to collagen-induced arthritis (CIA) rats after immunization. The secondary inflammatory reaction was evaluated by hind paw swelling, polyarthritis index and histopathological changes. Antibodies to type II collagen (CII) were determined by enzyme-linked immunosorbent assay (ELISA). Synoviocyte proliferations were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The expression of β-arrestins in synoviocytes from CIA rats was measured by western blot. The administration of TGP (25, 50, 100 mg/kg) depressed hind paw swelling and decreased the arthritis scores of CIA rats. TGP improved the pathologic manifestations of CIA. Serum anti-CII antibodies level increased significantly in CIA rats, while TGP had no effect on it. Fibroblast-like synoviocytes (FLS) proliferation was inhibited by TGP (50, 100 mg/kg). On d14, d28 after immunization, β-arrestins expression greatly up-regulated in synoviocytes from CIA rats and then returned to baseline levels on d42 after immunization. TGP (50, 100 mg/kg) significantly reduced the expression of β-arrestins. An inflammatory process in vivo induces an up-regulation of β-arrestins in synoviocytes from CIA rats while TGP can inhibit this change, which might be one of the important mechanisms for TGP to produce a marked therapeutic effect on RA. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

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Trentham, David E.; Dynesius-Trentham, Roselynn A.; Orav, E. John; Combitchi, Daniel; Lorenzo, Carlos; Sewell, Kathryn Lea; Hafler, David A.; Weiner, Howard L.

1993-09-01

Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.

Autoimmunity and inflammation are independent of class II transactivator type PIV-dependent class II major histocompatibility complex expression in peripheral tissues during collagen-induced arthritis.

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Waldburger, Jean-Marc; Palmer, Gaby; Seemayer, Christian; Lamacchia, Celine; Finckh, Axel; Christofilopoulos, Panayiotis; Baeten, Dominique; Reith, Walter; Gabay, Cem

2011-11-01

To determine the regulation of class II major histocompatibility complex (MHC) expression in fibroblast-like synoviocytes (FLS) in order to investigate their role as nonprofessional antigen-presenting cells in collagen-induced arthritis (CIA). Expression of class II MHC, class II MHC transactivator (CIITA), and Ciita isoforms PI, PIII, and PIV was examined by real-time quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry in human synovial tissues, arthritic mouse joints, and human and murine FLS. CIA was induced in mice in which isoform PIV of Ciita was knocked out (PIV(-/-) ), in PIV(-/-) mice transgenic for CIITA in the thymus (K14 CIITA), and in their control littermates. HLA-DRA, total CIITA, and CIITA PIII messenger RNA levels were significantly increased in synovial tissue samples from patients with rheumatoid arthritis compared with the levels in tissue from patients with osteoarthritis. Human FLS expressed surface class II MHC via CIITA PIII and PIV, while class II MHC expression in murine FLS was entirely mediated by PIV. Mice with a targeted deletion of CIITA PIV lack CD4+ T cells and were protected against CIA. The expression of CIITA was restored in the thymus of PIV(-/-) K14 CIITA-transgenic mice, which had a normal CD4+ T cell repertoire and normal surface levels of class II MHC on professional antigen-presenting cells, but did not induce class II MHC on FLS. Synovial inflammation and immune responses against type II collagen were similar in PIV(-/-) K14 CIITA-transgenic mice and control mice with CIA, but bone erosion was significantly reduced in the absence of PIV. Overexpression of class II MHC is tightly correlated with CIITA expression in arthritic synovium and in FLS. Selective targeting of Ciita PIV in peripheral tissues abrogates class II MHC expression by murine FLS but does not protect against inflammation and autoimmune responses in CIA. Copyright © 2011 by the American College of Rheumatology.

Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

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Spengler, Julia; Lugonja, Božo; Jimmy Ytterberg, A.; Zubarev, Roman A.; Creese, Andrew J.; Pearson, Mark J.; Grant, Melissa M.; Milward, Michael; Lundberg, Karin; Buckley, Christopher D.; Filer, Andrew; Raza, Karim; Cooper, Paul R.; Chapple, Iain L.

2015-01-01

Objective In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. Methods Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. Results Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. Conclusion Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA. PMID:26245941

Sterile Osteitis and Suppurative Arthritis Associated with Pannus Responding to Colchicine

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Mehmet Engin Tezcan

2013-01-01

Full Text Available Sterile suppurative arthritis is characterized by neutrophilic infiltration of joints without any causative pathogen. Here, we present a 32-year-old man with refractory osteitis and erosive suppurative oligoarthritis with pannus. Treatments with multiple disease modifying antirheumatic drugs were all unsuccessful. However, he had clinical response to colchicine and the synovial hypertrophy and the pannus in the MRI of his left shoulder resolved. In this case, the effects of colchicine on neutrophils might have played a role in treating neutrophilic sterile suppurative arthritis, which, in adults, might be a distinct oligoarticular disease.

Sterile osteitis and suppurative arthritis associated with pannus responding to colchicine.

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Tezcan, Mehmet Engin; Ekinci, Ozgür; Uçar, Murat; Göker, Berna

2013-01-01

Sterile suppurative arthritis is characterized by neutrophilic infiltration of joints without any causative pathogen. Here, we present a 32-year-old man with refractory osteitis and erosive suppurative oligoarthritis with pannus. Treatments with multiple disease modifying antirheumatic drugs were all unsuccessful. However, he had clinical response to colchicine and the synovial hypertrophy and the pannus in the MRI of his left shoulder resolved. In this case, the effects of colchicine on neutrophils might have played a role in treating neutrophilic sterile suppurative arthritis, which, in adults, might be a distinct oligoarticular disease.

Expression of soluble CD83 in plasma from early-stage rheumatoid arthritis patients is not modified by anti-TNF-alpha therapy

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Kristensen, Anne-Mette; Stengaard-Pedersen, Kristian; Hetland, Merete Lund

2017-01-01

Rheumatoid arthritis (RA) is an autoimmune disease which may lead to severe disabilities due to structural joint damage and extraarticular manifestations The dendritic cell marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with autoimmune diseases. In RA...... higher in synovial fluid than in plasma, and only a limited amount of membrane bound CD83 expression was detected on the surface of cells from peripheral blood and synovial fluid. Finally, confocal microscopy of RA synovial membranes revealed that CD83 was mainly localized intracellularly in a group...

Synovial tissue sublining CD68 expression is a biomarker of therapeutic response in rheumatoid arthritis clinical trials: consistency across centers.

LENUS (Irish Health Repository)

Bresnihan, Barry

2012-02-01

OBJECTIVE: To determine whether the correlation between the mean change in disease activity and the mean change in synovial sublining (sl) CD68 expression could be demonstrated across different academic centers. METHODS: Synovial biopsies obtained at arthroscopy from patients with rheumatoid arthritis before and 160 days after rituximab therapy were selected and coded. Paired sections were processed independently at Amsterdam Medical Center (AMC) and at St. Vincent\\'s University Hospital (SVUH), Dublin. Digital image analysis (DIA) was employed at both centers to quantify sublining CD68 expression. RESULTS: After analysis of CD68sl expression at centers in 2 different countries, high levels of intracenter and intercenter agreement were observed. For the pooled sections stained at AMC, the correlation between 2 investigators was R = 0.942, p = 0.000, and for sections stained at SVUH, R = 0.899, p = 0.001. Similarly, the intracenter correlations for DeltaCD68sl expression after treatment were R = 0.998, p = 0.000, for sections stained at AMC and R = 0.880, p = 0.000, for sections stained at SVUH. The intercenter correlation for the pooled scores of sections stained at AMC was R = 0.85, p = 0.000, and for the sections stained at SVUH, R = 0.62, p = 0.001. The consistent correlation between DeltaDAS (Disease Activity Score) and DeltaCD68sl expression across different studies (Pearson correlation = 0.895, p < 0.001) was confirmed. The standardized response mean values for DeltaCD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change. CONCLUSION: The correlation between mean DeltaDAS and mean DeltaCD68sl expression was confirmed across 2 centers. Examination of serial biopsy samples can be used reliably to screen for interesting biological effects at the site of inflammation at an early stage of drug development.

MRI findings of treated bacterial septic arthritis

International Nuclear Information System (INIS)

Bierry, Guillaume; Huang, Ambrose J.; Chang, Connie Y.; Torriani, Martin; Bredella, Miriam A.

2012-01-01

The purpose of this study was to report the MRI findings that can be encountered in successfully treated bacterial septic arthritis. The study included 12 patients (8 male and 4 female; mean age 38 years, range 9-85) with 13 proven cases of bacterial septic arthritis. The joints involved were hip (n = 3), knee (n = 3), shoulder (n = 2), sacroiliac (n = 2), ankle (n = 1), wrist (n = 1), and elbow (n = 1). MRI examinations following surgical debridement and at initiation of antibiotic therapy and after successful treatment were compared for changes in effusion, synovium, bone, and periarticular soft tissues. Imaging findings were correlated with microbiological and clinical findings. Joint effusions were present in all joints at baseline and regressed significantly at follow-up MRI (p = 0.001). Abscesses were present in 5 cases (38 %), and their sizes decreased significantly at follow-up (p = 0.001). Synovial enhancement and thickening were observed in all joints at both baseline and follow-up MRI. Myositis/cellulitis was present in 10 cases (77 %) at baseline and in 8 cases (62 %) at follow-up MRI. Bone marrow edema was present in 10 joints (77 %) at baseline and persisted in 8 joints (62 %). Bone erosions were found in 8 joints (62 %) and persisted at follow-up MRI in all cases. The sizes of joint effusions and abscesses appear to be the factors with the most potential for monitoring therapy for septic arthritis, since both decreased significantly following successful treatment. Synovial thickening and enhancement, periarticular myositis/cellulitis, and bone marrow edema can persist even after resolution of the infection. (orig.)

MRI findings of treated bacterial septic arthritis

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Bierry, Guillaume; Huang, Ambrose J.; Chang, Connie Y.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States)

2012-12-15

The purpose of this study was to report the MRI findings that can be encountered in successfully treated bacterial septic arthritis. The study included 12 patients (8 male and 4 female; mean age 38 years, range 9-85) with 13 proven cases of bacterial septic arthritis. The joints involved were hip (n = 3), knee (n = 3), shoulder (n = 2), sacroiliac (n = 2), ankle (n = 1), wrist (n = 1), and elbow (n = 1). MRI examinations following surgical debridement and at initiation of antibiotic therapy and after successful treatment were compared for changes in effusion, synovium, bone, and periarticular soft tissues. Imaging findings were correlated with microbiological and clinical findings. Joint effusions were present in all joints at baseline and regressed significantly at follow-up MRI (p = 0.001). Abscesses were present in 5 cases (38 %), and their sizes decreased significantly at follow-up (p = 0.001). Synovial enhancement and thickening were observed in all joints at both baseline and follow-up MRI. Myositis/cellulitis was present in 10 cases (77 %) at baseline and in 8 cases (62 %) at follow-up MRI. Bone marrow edema was present in 10 joints (77 %) at baseline and persisted in 8 joints (62 %). Bone erosions were found in 8 joints (62 %) and persisted at follow-up MRI in all cases. The sizes of joint effusions and abscesses appear to be the factors with the most potential for monitoring therapy for septic arthritis, since both decreased significantly following successful treatment. Synovial thickening and enhancement, periarticular myositis/cellulitis, and bone marrow edema can persist even after resolution of the infection. (orig.)

A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A.

LENUS (Irish Health Repository)

Mullan, Ronan Hugh

2012-02-01

Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression\\/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology\\/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial\\/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.

Leucocyte esterase in the rapid diagnosis of paediatric septic arthritis.

LENUS (Irish Health Repository)

Kelly, E G

2013-02-01

Septic arthritis may affect any age group but is more common in the paediatric population. Infection is generally bacterial in nature. Prompt diagnosis is crucial, as delayed treatment is associated with lifelong joint dysfunction. A clinical history and application of Kocher\\'s criteria may indicate that there is a septic arthritis. However, definitive diagnosis is made on culture of septic synovial fluid. The culture process can take over 24h for the initial culture to yield bacterial colonies. Leucocyte esterase is released by leucocytes at the site of an infection. We hypothesise that leucocyte esterase can be utilized in the rapid diagnosis of septic arthritis and shorten the time to decisive treatment whilst simultaneously decreasing unnecessary treatment of non-septic joints.

Magnetic Resonance Imaging Comparison of Intra-Articular Cavernous Synovial Hemangioma and Cystic Synovial Hyperplasia of the Knee

International Nuclear Information System (INIS)

De Filippo, M.; Rovani, C.; Sudberry, J. J.; Rossi, F.; Pogliacomi, F.; Zompatori, M.

2006-01-01

Purpose: To identify and compare magnetic resonance imaging (MRI) characteristics, with and without intravenous contrast medium, of cavernous synovial hemangiomas and cystic synovial hyperplasia. Material and Methods: Four cases of cavernous synovial hemangioma and five of cystic synovial hyperplasia of the knee were studied retrospectively. The patients (5 F and 4 M; 15-25 years of age) all had long-standing knee pain. At clinical examination we observed elastic swelling and pain without significant joint effusion. The patients underwent conventional radiography and MRI without and following intravenous contrast medium before arthroscopic biopsy. Results: The radiographs were interpreted as negative in all patients. MRI examination without contrast medium revealed a similar multicystic appearance for both lesions. Following intravenous contrast agent administration, cavernous synovial hemangiomas demonstrated avid, rather homogenous enhancement, whereas cystic synovial hyperplasia demonstrated less intense, peripheral enhancement only. Arthroscopy with histological examination of the lesions confirmed the MRI diagnosis in every case. Conclusion: In our experience, cavernous synovial hemangioma and cystic synovial hyperplasia have a similar appearance on unenhanced MRI, but can be reliably differentiated on the basis of enhancement characteristics following intravenous contrast administration. Keywords: Cavernous synovial hemangioma; cystic synovial hyperplasia; knee; MRI

Computational design and application of endogenous promoters for transcriptionally targeted gene therapy for rheumatoid arthritis.

NARCIS (Netherlands)

Geurts, J.; Joosten, L.A.B.; Takahashi, N.; Arntz, O.J.; Gluck, A.; Bennink, M.B.; Berg, W.B. van den; Loo, F.A.J. van de

2009-01-01

The promoter regions of genes that are differentially regulated in the synovial membrane during the course of rheumatoid arthritis (RA) represent attractive candidates for application in transcriptionally targeted gene therapy. In this study, we applied an unbiased computational approach to define

Targeting the Fas/FasL system in Rheumatoid Arthritis therapy: Promising or risky?

NARCIS (Netherlands)

Calmon-Hamaty, Flavia; Audo, Rachel; Combe, Bernard; Morel, Jacques; Hahne, Michael

2015-01-01

Rheumatoid Arthritis (RA) is a chronic inflammatory disease affecting synovial joints. Tumor necrosis factor (TNF) α is a key component of RA pathogenesis and blocking this cytokine is the most common strategy to treat the disease. Though TNFα blockers are very efficient, one third of the RA

The visualization of pannus in rheumatoid arthritis using NMR imaging. Pannusdarstellung bei rheumatoider Arthritis mittels Kernspintomographie

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Schnarkowski, P. (Abt. fuer Roentgendiagnostik, Klinikum der Univ. Ulm (Germany)); Bader, C. (Abt. fuer Roentgendiagnostik, Klinikum der Univ. Ulm (Germany)); Goldmann, A. (Abt. fuer Roentgendiagnostik, Klinikum der Univ. Ulm (Germany)); Friedrich, J.M. (Abt. fuer Roentgendiagnostik, Klinikum der Univ. Ulm (Germany))

1992-12-01

The knee joints of 15 patients afflicted with rheumatoid arthritis were investigated using the method of nmr imaging. Parameters of investigation were the spin-echo and fast-field-echo sequences as well as the MR signal behaviour of proliferative synovial changes following intravenous administration of gadolinium dtpa. Pannus having formed on the articular surfaces or beneath the articular cartilages was distinguishable from other changes on the basis of the increased signal intensities to be observed after gadolinium dtpa had been given. (orig./GD)

Salmonella enteridis Septic Arthritis: A Report of Two Cases

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Esat Uygur

2013-01-01

Full Text Available Introduction. Nontyphoidal salmonellosis causes significant morbidity, is transmitted via fecal-oral route, and is a worldwide cause of gastroenteritis, bacteremia, and local infections. Salmonella is a less common etiologic factor for septic arthritis compared with other gram-negative bacteria. Cases. We present two septic arthritis cases with Salmonella enteridis as a confirmed pathogen and also discuss the predisposing factors and treatment. Discussion. Septic arthritis is an orthopedic emergency. The gold standard treatment of septic arthritis is joint debridement, antibiotic therapy according to the culture results, and physiotherapy, which should start in the early postoperative period to prevent limitation of motion. Salmonella is an atypical agent for septic arthritis. It must be particularly kept in mind as an etiologic factor for the acute arthritis of a patient with sickle cell anemia and systemic lupus erythematosus. Clinicians should be cautious that the white blood cell count in synovial fluid can be under 50.000/mm3 in immune compromised individuals with septic arthritis. The inflammatory response can be deficient, or the microorganism may be atypical. Conclusion. Atypical bacteria such as Salmonella species in immune compromised patients can cause joint infections. Therefore, Salmonella species must always be kept in mind for the differential diagnosis of septic arthritis in a clinically relevant setting.

The initial ultrasonographic examination of hands and feet joints in patients with early rheumatoid arthritis

Directory of Open Access Journals (Sweden)

Monika Ponikowska

2015-09-01

Full Text Available Objectives : The aim was to assess of the morphology, intensity, and activity of changes in the first ultrasonographic (US examination of hands and feet in patients with early arthritis (lasting up to 12 months who were ultimately diagnosed with rheumatoid arthritis (RA. An attempt was made to demonstrate a correlation between the intensity of lesions in US and selected laboratory parameters. Material and methods : Ultrasonographic examination was performed using a LOGIC GE 500 device on a group of 60 patients with arthritis (46 women, 14 men aged 18–80, previously untreated. In total, 3120 hand and feet joints were examined. The assessment focused on the presence of joint effusion, synovial proliferation and power Doppler signals (assessed on a semi-quantitative scale. Each patient underwent laboratory tests, necessary for making a diagnosis. In order to analyze the correlations between changes in US and laboratory parameters, erythrocyte sedimentation rate (ESR, reactive protein test (CRP, rheumatoid factor (RF, and anti-citrullinated protein antibodies (ACPAs were used. Results : In the study group, the average duration of arthritis symptoms until the first US examination was 5.6 months. Among the 3120 examined hand and foot joints, deviations from the norm appeared in 1093 joints, synovial hypertrophy was found in 471 joints (grade 1 synovial hypertrophy was reported most frequently, while presence of signal in Power Doppler was revealed in 261 joints (grade 1 was observed most frequently. A statistically significant correlation was found between the intensity of changes in Power Doppler and CRP concentration. Conclusions : In patients with increased concentrations of CRP, we may expect arthritis of higher intensity, therefore, in order to prevent the progression of destructive changes, it is necessary to quickly implement effective disease-modifying antirheumatic treatment. The conducted research showed that the activity of joint

Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation

DEFF Research Database (Denmark)

Chockalingam, P S; Glasson, S S; Lohmander, Stefan

2013-01-01

meniscus lesions, isolated knee meniscus injury, acute inflammatory arthritis (AIA) and knee osteoarthritis (OA). TN-C was measured in synovial fluid samples using an enzyme-linked immunosorbent assay (ELISA) and results correlated to other cartilage markers. TN-C release was also monitored in joints...

Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients?

NARCIS (Netherlands)

Loo, F.A.J. van de; Smeets, R.L.L.; Berg, W.B. van den

2004-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints, with progressive destruction of cartilage and bone. Anti-tumour necrosis factor-alpha therapies (e.g. soluble tumour necrosis factor receptors) ameliorate disease in 60-70% of patients with RA. However, the need for

Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.

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Jyh-Horng Wang

Full Text Available Fibroblast-like synoviocytes (FLS play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs. The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5'-Diallyl-biphenyl-2,2'-diol, the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E(2, and matrix metalloproteinases (MMPs by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL-induced cytokine expression in a concentration-dependent manner (2.5-25 µg/mL. In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases.

Gram staining in the diagnosis of acute septic arthritis.

Science.gov (United States)

Faraj, A A; Omonbude, O D; Godwin, P

2002-10-01

This study aimed at determining the sensitivity and specificity of Gram staining of synovial fluid as a diagnostic tool in acute septic arthritis. A retrospective study was made of 22 patients who had arthroscopic lavage following a provisional diagnosis of acute septic arthritis of the knee joint. Gram stains and cultures of the knee aspirates were compared with the clinical and laboratory parameters, to evaluate their usefulness in diagnosing acute arthritis. All patients who had septic arthritis had pain, swelling and limitation of movement. CRP was elevated in 90% of patients. The incidence of elevated white blood cell count was higher in the group of patients with a positive Gram stain study (60%) as compared to patients with a negative Gram stain study (33%). Gram staining sensitivity was 45%. Its specificity was however 100%. Gram staining is an unreliable tool in early decision making in patients requiring urgent surgical drainage and washout.

Case report 511: Fibroblastic rheumatism

International Nuclear Information System (INIS)

Hernandez, R.J.; Martel, W.; Headington, J.T.; Kaufman, R.A.; Cincinnati Univ., OH

1989-01-01

We report a ten-year-old child with the newly described entity of fibroblastic rheumatism. This child developed rapid, progressive, symmetrical polyarthritis, similar to the radiographic appearance of juvenile rheumatoid arthritis, except for the rapidity of progression. The polyarthritis was preceded by the development of skin nodules with characteristic histological changes. (orig./GDG)

FoxP3 mRNA splice forms in synovial CD4+ T cells in rheumatoid arthritis and psoriatic arthritis

DEFF Research Database (Denmark)

Ryder, L Rebekka; Bartels, Else Marie; Woetmann, Anders

2012-01-01

Our aim was to elucidate the relative amount of the different splice forms of FoxP3 mRNA in CD4+ T cells in peripheral blood (PB) compared to synovial fluid (SF) in RA and PsA patients. FoxP3 mRNA was measured using a quantitative real-time PCR method. CD4+ T cells were isolated from 17 paired...... samples of PB and SF from RA and PsA patients, and PB from 10 controls. FoxP3fl and FoxP3Δ2 mRNA was significantly increased (6.7 and 2.1-fold, respectively) in PB CD4+ T cells from RA patients compared to controls. FoxP3fl and Δ2 mRNA in SF CD4+ T cells was increased compared to controls in sero......-negative RA and PsA, but not in sero-positive RA patients, who had a high FoxP3 expression in both PB and SF. The FoxP3Δ2Δ7 mRNA was barely detectable in patient samples, and not at all in healthy individuals. We provide evidence of an increased expression of FoxP3 splice forms in synovial CD4+ T cells from...

Avastin exhibits therapeutic effects on collagen-induced arthritis in rat model.

Science.gov (United States)

Wang, Yong; Da, Gula; Li, Hongbin; Zheng, Yi

2013-12-01

Avastin is the monoclonal antibody for vascular endothelial growth factor (VEGF). This study aimed to investigate therapeutic effect of Avastin on type II collagen-induced arthritis. Type II chicken collagen was injected into the tails of Wistar rats, and 60 modeled female rats were randomly divided into three groups (n = 20): Avastin group, Etanercept group, and control group. Arthritis index and joint pad thickness were scored, and the pathology of back metapedes was analyzed. The results showed that compared to control group, the arthritis index, target-to-non-target ratio, synovial pathological injury index, serum levels of VEGF and tumor necrosis factor alpha, and VEGF staining were decreased significantly 14 days after Avastin or Etanercept treatment, but there were no significant differences between Avastin group and Etanercept group. These data provide evidence that Avastin exhibits similar effects to Etanercept to relieve rheumatoid arthritis in rat model and suggest that Avastin is a promising therapeutic agent for rheumatoid arthritis.

Transport mechanisms and their pathology-induced regulation govern tyrosine kinase inhibitor delivery in rheumatoid arthritis.

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Christian Schmidt-Lauber

Full Text Available BACKGROUND: Tyrosine kinase inhibitors (TKIs are effective in treating malignant disorders and were lately suggested to have an impact on non-malignant diseases. However, in some inflammatory conditions like rheumatoid arthritis (RA the in vivo effect seemed to be moderate. As most TKIs are taken up actively into cells by cell membrane transporters, this study aimed to evaluate the role of such transporters for the accumulation of the TKI Imatinib mesylates in RA synovial fibroblasts as well as their regulation under inflammatory conditions. METHODOLOGY/PRINCIPAL FINDINGS: The transport and accumulation of Imatinib was investigated in transporter-transfected HEK293 cells and human RA synovial fibroblasts (hRASF. Transporter expression was quantified by qRT-PCR. In transfection experiments, hMATE1 showed the highest apparent affinity for Imatinib among all known Imatinib transporters. Experiments quantifying the Imatinib uptake in the presence of specific transporter inhibitors and after siRNA knockdown of hMATE1 indeed identified hMATE1 to mediate Imatinib transport in hRASF. The anti-proliferative effect of Imatinib on PDGF stimulated hRASF was quantified by cell counting and directly correlated with the uptake activity of hMATE1. Expression of hMATE1 was investigated by Western blot and immuno-fluorescence. Imatinib transport under disease-relevant conditions, such as an altered pH and following stimulation with different cytokines, was also investigated by HPLC. The uptake was significantly reduced by an acidic extracellular pH as well as by the cytokines TNFα, IL-1β and IL-6, which all decreased the expression of hMATE1-mRNA and protein. CONCLUSION/SIGNIFICANCE: The regulation of Imatinib uptake via hMATE1 in hRASF and resulting effects on their proliferation may explain moderate in vivo effects on RA. Moreover, our results suggest that investigating transporter mediated drug processing under normal and pathological conditions is important

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

LENUS (Irish Health Repository)

Guo, Yanxia

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA\\/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

Science.gov (United States)

Guo, Yanxia; Walsh, Alice M; Canavan, Mary; Wechalekar, Mihir D; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M; Pitzalis, Costantino; Smith, Malcolm D; Friedman, Joshua R; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J; Fearon, Ursula; Nagpal, Sunil

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

Non-Enzymatic Decomposition of Collagen Fibers by a Biglycan Antibody and a Plausible Mechanism for Rheumatoid Arthritis

Energy Technology Data Exchange (ETDEWEB)

Antipova, Olga; Orgel, Joseph P.R.O. (IIT)

2013-04-08

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory and destructive joint disorder that affects tens of millions of people worldwide. Normal healthy joints maintain a balance between the synthesis of extracellular matrix (ECM) molecules and the proteolytic degradation of damaged ones. In the case of RA, this balance is shifted toward matrix destruction due to increased production of cleavage enzymes and the presence of (autoimmune) immunoglobulins resulting from an inflammation induced immune response. Herein we demonstrate that a polyclonal antibody against the proteoglycan biglycan (BG) causes tissue destruction that may be analogous to that of RA affected tissues. The effect of the antibody is more potent than harsh chemical and/or enzymatic treatments designed to mimic arthritis-like fibril de-polymerization. In RA cases, the immune response to inflammation causes synovial fibroblasts, monocytes and macrophages to produce cytokines and secrete matrix remodeling enzymes, whereas B cells are stimulated to produce immunoglobulins. The specific antigen that causes the RA immune response has not yet been identified, although possible candidates have been proposed, including collagen types I and II, and proteoglycans (PG's) such as biglycan. We speculate that the initiation of RA associated tissue destruction in vivo may involve a similar non-enzymatic decomposition of collagen fibrils via the immunoglobulins themselves that we observe here ex vivo.

Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway.

Science.gov (United States)

Mun, Se Hwan; Kim, Hyuk Soon; Kim, Jie Wan; Ko, Na Young; Kim, Do Kyun; Lee, Beob Yi; Kim, Bokyung; Won, Hyung Sik; Shin, Hwa-Sup; Han, Jeung-Whan; Lee, Hoi Young; Kim, Young Mi; Choi, Wahn Soo

2009-09-01

We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway.

Stromal cells and osteoclasts are responsible for exacerbated collagen-induced arthritis in interferon-beta-deficient mice

DEFF Research Database (Denmark)

Treschow, Alexandra P; Teige, Ingrid; Nandakumar, Kutty S

2005-01-01

OBJECTIVE: Clinical trials using interferon-beta (IFNbeta) in the treatment of rheumatoid arthritis have shown conflicting results. We undertook this study to understand the mechanisms of IFNbeta in arthritis at a physiologic level. METHODS: Collagen-induced arthritis (CIA) was induced in IFNbeta....... Differences in osteoclast maturation were determined in situ by histology of arthritic and naive paws and by in vitro maturation studies of naive bone marrow cells. The importance of IFNbeta-producing fibroblasts was determined by transferring fibroblasts into mice at the time of CIA immunization. RESULTS...

Sphingolipids in human synovial fluid--a lipidomic study.

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Marta Krystyna Kosinska

Full Text Available Articular synovial fluid (SF is a complex mixture of components that regulate nutrition, communication, shock absorption, and lubrication. Alterations in its composition can be pathogenic. This lipidomic investigation aims to quantify the composition of sphingolipids (sphingomyelins, ceramides, and hexosyl- and dihexosylceramides and minor glycerophospholipid species, including (lysophosphatidic acid, (lysophosphatidylglycerol, and bis(monoacylglycerophosphate species, in the SF of knee joints from unaffected controls and from patients with early (eOA and late (lOA stages of osteoarthritis (OA, and rheumatoid arthritis (RA. SF without cells and cellular debris from 9 postmortem donors (control, 18 RA, 17 eOA, and 13 lOA patients were extracted to measure lipid species using electrospray ionization tandem mass spectrometry--directly or coupled with hydrophilic interaction liquid chromatography. We provide a novel, detailed overview of sphingolipid and minor glycerophospholipid species in human SF. A total of 41, 48, and 50 lipid species were significantly increased in eOA, lOA, and RA SF, respectively when compared with normal SF. The level of 21 lipid species differed in eOA SF versus SF from lOA, an observation that can be used to develop biomarkers. Sphingolipids can alter synovial inflammation and the repair responses of damaged joints. Thus, our lipidomic study provides the foundation for studying the biosynthesis and function of lipid species in health and most prevalent joint diseases.

Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis

NARCIS (Netherlands)

Maurice, M. M.; Nakamura, H.; Gringhuis, S.; Okamoto, T.; Yoshida, S.; Kullmann, F.; Lechner, S.; van der Voort, E. A.; Leow, A.; Versendaal, J.; Muller-Ladner, U.; Yodoi, J.; Tak, P. P.; Breedveld, F. C.; Verweij, C. L.

1999-01-01

OBJECTIVE: To examine the expression of the thioredoxin (TRX)-thioredoxin reductase (TR) system in patients with rheumatoid arthritis (RA) and patients with other rheumatic diseases. METHODS: Levels of TRX in plasma and synovial fluid (SF) were measured using enzyme-linked immunosorbent assay.

The Roles of Interleukin-6 in the Pathogenesis of Rheumatoid Arthritis

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Misato Hashizume

2011-01-01

Full Text Available Several clinical studies have demonstrated that the humanized anti-interleukin-6 (IL-6 receptor antibody tocilizumab (TCZ improves clinical symptoms and prevents progression of joint destruction in rheumatoid arthritis (RA. However, the precise mechanism by which IL-6 blockade leads to the improvement of RA is not well understood. IL-6 promotes synovitis by inducing neovascularization, infiltration of inflammatory cells, and synovial hyperplasia. IL-6 causes bone resorption by inducing osteoclast formation via the induction of RANKL in synovial cells, and cartilage degeneration by producing matrix metalloproteinases (MMPs in synovial cells and chondrocytes. Moreover, IL-6 is involved in autoimmunity by altering the balance between Th17 cells and Treg. IL-6 also acts on changing lipid concentrations in blood and on inducing the production of hepcidin which causes iron-deficient anemia. In conclusion, IL-6 is a major player in the pathogenesis of RA, and current evidence indicates that the blockade of IL-6 is a beneficial therapy for RA patients.

Potential of Topical Curcumin in Reduction of TNF-α expression and Synovium Hyperplasia on Wistar Rats of Rheumatoid Arthritis Model

OpenAIRE

Ferri Widodo; Diana Lyrawati; Bagus Putu Putra Suryana

2016-01-01

Rheumatoid arthritis is a chronic inflammatory autoimmune disease associated with articular and systemic effects. This disease affects synovial joints covered by a special tissue called synovium. Curcumin has a potent antioxidant, antiinflammatory agent, antiangiogenic and anticarcinogenic. Curcumin can downregulate the expression of various proinflammatory cytokines and is reported beneficial effects in arthritis, but has a poor solubility dan bioavailability as well. The purpose of this res...

Proinflammatory Soluble Interleukin-15 Receptor Alpha Is Increased in Rheumatoid Arthritis

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Ana Cecilia Machado Diaz

2012-01-01

Full Text Available Rheumatoid arthritis (RA is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA in samples of synovial fluid from patients with RA and osteoarthritis (OA. The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.

Ultrasonographic findings of septic arthritis and osteomyelitis in neonatal hip

International Nuclear Information System (INIS)

Lee, Seung Hoon; Jung, Kun Sik; Koh, Jung Kon; Im, Myung Ah; Kwon, Kwi Ryun; Kim, Sung Soo

2000-01-01

To evaluate ultrasonographic findings of neonatal patients who confirmed and treated as hip joint septic arthritis and osteomyelitis. We retrospectively examined clinical feature and radiologic findings of 7 neonatal patients ranging from 8 to 28 days of age who were examined from January 1966 to December 1998 at nursery and were confirmed and treated on the diagnosis of septic arthritis and osteomyelitis. Clinical features of the patients were comparatively analyzed with radiologic findings including plain radiographs, ultrasonography, bone scan and MRI. We emphasized importance of ultrasonographic findings of these patients. Ultrasonography was performed first of all in all cases after the symptom onset. Other examinations were performed on the same day or a few days later after ultrasonography. Ultrasonography revealed abnormal finding in 85.7% (6/7) of all cases. Plain radiographs revealed abnormal findings in 28.6% (2/7). Bone scan revealed decreased uptake in 66.7%(2/3). MRI revealed abnormal signal intensity in 100%(3/3). Ultrasonographic findings of the patients were deep soft swelling in 85.7% (6/7) of all cases, periosteal elevation in 57.1% (4/7), synovial thickening in 42.8% (3/7), synovial effusion in 42.8%(3/7), echogenic debris or clot in 28.5% (2/7), cortical erosion in 28.5% (2/7), and subperiosteal abscess in 14.2% (1/7). Ultrasonography is a useful modality to diagnose septic arthritis and osteomyelitis in neonatal hip.

Gram and acridine orange staining for diagnosis of septic arthritis in different patient populations.

Science.gov (United States)

Cunningham, Gregory; Seghrouchni, Khalid; Ruffieux, Etienne; Vaudaux, Pierre; Gayet-Ageron, Angèle; Cherkaoui, Abdessalam; Godinho, Eduardo; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

2014-06-01

The sensitivity of Gram staining is known to be suboptimal for the diagnosis of native joint septic arthritis. We lack information about the accuracy of Gram compared to other microscopic staining techniques for predicting infection in different patient populations. This was a cohort study with cost evaluations at the Orthopaedic Service of Geneva University Hospitals (January 1996-October 2012). Among 500 episodes of arthritis (196 with immunosuppression, 227 with underlying arthroplasties and 69 with gout or other crystals in synovial fluid), Gram staining revealed pathogens in 146 episodes (146/500, 29 %) or in 146 of the 400 culture-positive episodes (37 %). Correlation between the Gram and acridine staining of the same sample was good (Spearman 0.85). Overall, the sensitivity, specificity, positive predictive value and negative predictive value of Gram stain for rapid diagnosis of septic arthritis was 0.37, 0.99, 0.99 and 0.28, respectively, compared to microbiological cultures. Quite similar values were recorded across the different patient subpopulations, in particular for sensitivity values that were 0.33 for patients with prosthetic joint infections, 0.40 for immunosuppressed patients, 0.36 for patients under antibiotic administration and 0.52 for patients with concomitant crystalline disease. The sensitivity of Gram or acridine orange staining for a rapid diagnosis of episodes of septic arthritis is suboptimal compared to microbiological culture, regardless of underlying conditions, immunosuppression or antibiotic therapy. The sensitivity in the presence of synovial fluid crystals is moderate. Acridine orange and Gram stains are equivalent.

[Imaging of the elbow joint with focus MRI. Part 2: muscles, nerves and synovial membranes].

Science.gov (United States)

Rehm, J; Zeifang, F; Weber, M-A

2014-03-01

This review article discusses the magnetic resonance imaging (MRI) features and pathological changes of muscles, nerves and the synovial lining of the elbow joint. Typical imaging findings are illustrated and discussed. In addition, the cross-sectional anatomy and anatomical variants, such as accessory muscles and plicae are discussed. Injuries of the muscles surrounding the elbow joint, as well as chronic irritation are particularly common in athletes. Morphological changes in MRI, for example tennis or golfer's elbow are typical and often groundbreaking. By adapting the examination sequences, imaging planes and slices, complete and incomplete tendon ruptures can be reliably diagnosed. Although the clinical and electrophysiological examinations form the basis for the diagnosis of peripheral neuropathies, MRI provides useful additional information about the precise localization due to its high resolution and good soft tissue contrast and helps to rule out differential diagnoses. Synovial diseases, such as inflammatory arthritis, proliferative diseases and also impinging plicae must be considered in the MRI diagnostics of the elbow joint.

Photoacoustic and ultrasound dual-modality imaging for inflammatory arthritis

Science.gov (United States)

Xu, Guan; Chamberland, David; Girish, Gandikota; Wang, Xueding

2014-03-01

Arthritis is a leading cause of disability, affecting 46 million of the population in the U.S. Rendering new optical contrast in articular tissues at high spatial and temporal resolution, emerging photoacoustic imaging (PAI) combined with more established ultrasound (US) imaging technologies provides unique opportunities for diagnosis and treatment monitoring of inflammatory arthritis. In addition to capturing peripheral bone and soft tissue images, PAI has the capability to quantify hemodynamic properties including regional blood oxygenation and blood volume, both abnormal in synovial tissues affected by arthritis. Therefore, PAI, especially when performed together with US, should be of considerable help for further understanding the pathophysiology of arthritis as well as assisting in therapeutic decisions, including assessing the efficacy of new pharmacological therapies. In this paper, we will review our recent work on the development of PAI for application to the diagnostic imaging and therapeutic monitoring of inflammatory arthritis. We will present the imaging results from a home-built imaging system and another one based on a commercial US. The performance of PAI in evaluating pharmacological therapy on animal model of arthritis will be shown. Moreover, our resent work on PAI and US dual-modality imaging of human peripheral joints in vivo will also be presented.

The dual regulation of substance P-mediated inflammation via human synovial mast cells in rheumatoid arthritis

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Yuki Okamura

2017-09-01

Conclusions: Activated synovial MCs may rapidly degrade SP, which may downregulate the SP-mediated activation of synoviocytes in RA. On the other hand, SP activates MCs to induce inflammatory mediators, suggesting the dual regulation of SP-mediated inflammation by MCs in RA.

Aetiology of arthritis in hospitalised children: an observational study.

Science.gov (United States)

Aupiais, Camille; Ilharreborde, Brice; Doit, Catherine; Blachier, Audrey; Desmarest, Marie; Job-Deslandre, Chantal; Mazda, Keyvan; Faye, Albert; Bonacorsi, Stéphane; Alberti, Corinne; Lorrot, Mathie

2015-08-01

Arthritis in children has many causes and includes septic and viral arthritis, reactive arthritis and juvenile idiopathic arthritis (JIA). We aimed to describe the different types of arthritis among children hospitalised for a first episode of arthritis. Retrospective, descriptive case series study. A French tertiary care centre. Children under 16 years of age hospitalised for an arthritis episode between 1 January 2008 and 31 December 2009. Demographic and clinical features were compared with χ(2) or Fisher's exact tests and non-parametric tests. 173 children were hospitalised for a first episode of arthritis during the study period, with a male/female ratio of 1.14. The most frequent cause of hospitalisation was septic arthritis (43.4% of cases, 69.3% of which were due to Kingella kingae and 10.7% to Staphylococcus aureus). JIA was responsible for 8.1% of cases and arthritis without any definitive diagnosis for 40.4%. Median age at diagnosis was 2.7 years (IQR 0.3-14.6) and was lower in the septic arthritis group (1.5 years; 1.1-3.4) than in the JIA group (4.7 years; 2.5-10.9) (p<0.01). Septic arthritis involved a single joint in 97.3% of cases, while JIA involved four joints in 14.3% of cases and two to four joints in 28.6% of cases (p<0.01). Septic arthritis was the most frequent cause of arthritis in hospitalised children. Despite the increasing application of microbiological molecular methods to synovial fluid analysis, further measures are required to improve the diagnosis of arthritis of unknown cause. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Methyl salicylate lactoside inhibits inflammatory response of fibroblast-like synoviocytes and joint destruction in collagen-induced arthritis in mice.

Science.gov (United States)

Xin, Wenyu; Huang, Chao; Zhang, Xue; Xin, Sheng; Zhou, Yiming; Ma, Xiaowei; Zhang, Dan; Li, Yongjie; Zhou, Sibai; Zhang, Dongming; Zhang, Tiantai; Du, Guanhua

2014-07-01

Methyl salicylate 2-O-β-d-lactoside (MSL), whose chemical structure is similar to that of salicylic acid, is a natural product derivative isolated from a traditional Chinese herb. The aim of this study was to investigate the therapeutic effect of MSL in mice with collagen-induced arthritis (CIA) and explore its underlying mechanism. The anti-arthritic effects of MSL were evaluated on human rheumatoid fibroblast-like synoviocytes (FLS) in vitro and CIA in mice in vivo by obtaining clinical scores, measuring hind paw thickness and inflammatory cytokine levels, radiographic evaluations and histopathological assessments. Treatment with MSL after the onset of arthritis significantly prevented the progression and development of rheumatoid arthritis (RA) in CIA mice without megascopic gastric mucosa damage. In addition, MSL inhibited the production of pro-inflammatory mediators, the phosphorylation and translocation of NF-κB, and cell proliferation induced by TNF-α in FLS. MSL non-selectively inhibited the activity of COX in vitro, but was a more potent inhibitor of COX-2 than COX-1. MSL also inhibited the phosphorylation of inhibitor of NF-κB kinase, IκBα and p65, thus blocking the nuclear translocation of NF-κB in TNF-α-stimulated FLS. MSL exerts therapeutic effects on CIA mice, suppressing the inflammatory response and joint destruction by non-selectively inhibiting the activity of COX and suppressing activation of the NF-κB signalling pathway, but without damaging the gastric mucosa. Therefore, MSL has great potential to be developed into a novel therapeutic agent for the treatment of RA. © 2014 The British Pharmacological Society.

Synovial osteochondromatosis of the temporomandibular joint

International Nuclear Information System (INIS)

Nemnon, Jorge; Nemnon, Marcelo; Staffieri, Roberto; Villavicencio, C.; Marconi, G.; Masjoan, Diego

2004-01-01

Synovial osteochondromatosis (SO) is a meta plastic process by which synovial mesenchymal cells transform into chondroblasts and chondrocytes. This disease affects most frequently the knee, the hip, the elbow, and uncommonly the temporomandibular joint (TMJ). The authors present 2 cases of synovial osteochondromatosis of the TMJ. (author)

Synovial folds in equine articular process joints

DEFF Research Database (Denmark)

Thomsen, Line Nymann; Berg, Lise Charlotte; Markussen, Bo

2013-01-01

Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses.......Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses....

Sulforaphane Modulates Joint Inflammation in a Murine Model of Complete Freund’s Adjuvant-Induced Mono-Arthritis

Directory of Open Access Journals (Sweden)

João Francisco Silva Rodrigues

2018-04-01

Full Text Available Rheumatoid arthritis (RA is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund’s Adjuvant (CFA-10 µg/joint, in 10 µL into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg or vehicle (3% DMSO in saline, intraperitoneally (i.p., twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C+ and Ly6G+ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G+ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation.

Legionella Bozemanae, a New Cause of Septic Arthritis diagnosed by 16S PCR followed by specific culture

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Just, Søren Andreas; Bonde Knudsen, John; Skov, Marianne Nielsine

This is the first report ever to demonstrate that L. Bozemanae can colonize synovial joints leading to infectious arthritis. L. Bozemanae is a rare Legionella species, earlier described as a cause of cavitating lung infections with up to 40% mortality (2). L. Bozemanae is missed by standard...

DNA Methylome Signature in Synoviocytes From Patients With Early Rheumatoid Arthritis Compared to Synoviocytes From Patients With Longstanding Rheumatoid Arthritis

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Ai, Rizi; Whitaker, John W.; Boyle, David L.; Tak, Paul Peter; Gerlag, Danielle M.; Wang, Wei; Firestein, Gary S.

2015-01-01

Epigenetics can contribute to pathogenic mechanisms in autoimmunity. We recently identified an imprinted DNA methylation pattern in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) involving multiple genes in pathways implicated in cell migration, matrix regulation and immune

A model of synovial fluid lubricant composition in normal and injured joints

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M E Blewis

2007-03-01

Full Text Available The synovial fluid (SF of joints normally functions as a biological lubricant, providing low-friction and low-wear properties to articulating cartilage surfaces through the putative contributions of proteoglycan 4 (PRG4, hyaluronic acid (HA, and surface active phospholipids (SAPL. These lubricants are secreted by chondrocytes in articular cartilage and synoviocytes in synovium, and concentrated in the synovial space by the semi-permeable synovial lining. A deficiency in this lubricating system may contribute to the erosion of articulating cartilage surfaces in conditions of arthritis. A quantitative intercompartmental model was developed to predict in vivo SF lubricant concentration in the human knee joint. The model consists of a SF compartment that (a is lined by cells of appropriate types, (b is bound by a semi-permeable membrane, and (c contains factors that regulate lubricant secretion. Lubricant concentration was predicted with different chemical regulators of chondrocyte and synoviocyte secretion, and also with therapeutic interventions of joint lavage and HA injection. The model predicted steady-state lubricant concentrations that were within physiologically observed ranges, and which were markedly altered with chemical regulation. The model also predicted that when starting from a zero lubricant concentration after joint lavage, PRG4 reaches steady-state concentration ~10-40 times faster than HA. Additionally, analysis of the clearance rate of HA after therapeutic injection into SF predicted that the majority of HA leaves the joint after ~1-2 days. This quantitative intercompartmental model allows integration of biophysical processes to identify both environmental factors and clinical therapies that affect SF lubricant composition in whole joints.

Synovial sarcoma of the abdominal wall

International Nuclear Information System (INIS)

Matushita, J.P.K.; Matushita, J.S.

1989-01-01

A case report of synovial sarcoma arising in the abdominal wall is presented. A brief review of the clinical and radiological features of synovial sarcoma is made. Pre-operative diagnosis of an abdominal wall synovial sarcoma is virtually impossible, but should be considered when a soft tissue swelling is found to show amorphous stippled calcification X-ray. (author) [pt

A dynamic real time in vivo and static ex vivo analysis of granulomonocytic cell migration in the collagen-induced arthritis model.

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Ruth Byrne

Full Text Available Neutrophilic granulocytes and monocytes (granulomonocytic cells; GMC drive the inflammatory process at the earliest stages of rheumatoid arthritis (RA. The migratory behavior and functional properties of GMC within the synovial tissue are, however, only incompletely characterized. Here we have analyzed GMC in the murine collagen-induced arthritis (CIA model of RA using multi-photon real time in vivo microscopy together with ex vivo analysis of GMC in tissue sections.GMC were abundant as soon as clinical arthritis was apparent. GMC were motile and migrated randomly through the synovial tissue. In addition, we observed the frequent formation of cell clusters consisting of both neutrophilic granulocytes and monocytes that actively contributed to the inflammatory process of arthritis. Treatment of animals with a single dose of prednisolone reduced the mean velocity of cell migration and diminished the overall immigration of GMC.In summary, our study shows that the combined application of real time in vivo microscopy together with elaborate static post-mortem analysis of GMC enables the description of dynamic migratory characteristics of GMC together with their precise location in a complex anatomical environment. Moreover, this approach is sensitive enough to detect subtle therapeutic effects within a very short period of time.

Euglena gracilis Z and its carbohydrate storage substance relieve arthritis symptoms by modulating Th17 immunity.

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Kengo Suzuki

Full Text Available Euglena gracilis Z is a microorganism classified as a microalga and is used as a food or nutritional supplement. Paramylon, the carbohydrate storage substance of E. gracilis Z, is reported to affect the immunological system. This study evaluated the symptom-relieving effects of E. gracilis Z and paramylon in rheumatoid arthritis in a collagen-induced arthritis mouse model. The efficacy of both substances was assessed based on clinical arthritis signs, as well as cytokine (interleukin [IL]-17, IL-6, and interferon [IFN]-γ levels in lymphoid tissues. Additionally, the knee joints were harvested and histopathologically examined. The results showed that both substances reduced the transitional changes in the visual assessment score of arthritis symptoms compared with those in the control group, indicating their symptom-relieving effects on rheumatoid arthritis. Furthermore, E. gracilis Z and paramylon significantly reduced the secretion of the cytokines, IL-17, IL-6, and IFN-γ. The histopathological examination of the control group revealed edema, inflammation, cell hyperplasia, granulation tissue formation, fibrosis, and exudate in the synovial membrane, as well as pannus formation and articular cartilage destruction in the femoral trochlear groove. These changes were suppressed in both treatment groups. Particularly, the E. gracilis Z group showed no edema, inflammation, and fibrosis of the synovial membrane, or pannus formation and destruction of articular cartilage in the femoral trochlear groove. Furthermore, E. gracilis Z and paramylon exhibited symptom-relieving effects on rheumatoid arthritis and suppressed the secretion of cytokines IL-17, IL-6, and IFN-γ. These effects were likely mediated by the regulatory activities of E. gracilis Z and paramylon on Th17 immunity. In addition, the symptom-relieving effects of both substances were comparable, which suggests that paramylon is the active component of Euglena gracilis Z.

Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy.

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Baeten, Dominique; Kruithof, Elli; De Rycke, Leen; Boots, Anemieke M; Mielants, Herman; Veys, Eric M; De Keyser, Filip

2005-01-01

Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features of synovium reflect specific phenotypes and/or global disease activity in SpA. Synovial biopsies obtained from 99 SpA and 86 RA patients with active knee synovitis were analyzed for 15 histological and immunohistochemical markers. Correlations with swollen joint count, serum C-reactive protein concentrations, and erythrocyte sedimentation rate were analyzed using classical and multiparameter statistics. SpA synovitis was characterized by higher vascularity and infiltration with CD163+ macrophages and polymorphonuclear leukocytes (PMNs) and by lower values for lining-layer hyperplasia, lymphoid aggregates, CD1a+ cells, intracellular citrullinated proteins, and MHC-HC gp39 complexes than RA synovitis. Unsupervised clustering of the SpA samples based on synovial features identified two separate clusters that both contained different SpA subtypes but were significantly differentiated by concentration of C-reactive protein and erythrocyte sedimentation rate. Global disease activity in SpA correlated significantly with lining-layer hyperplasia as well as with inflammatory infiltration with macrophages, especially the CD163+ subset, and with PMNs. Accordingly, supervised clustering using these synovial parameters identified a cluster of 20 SpA patients with significantly higher disease activity, and this finding was confirmed in an independent SpA cohort. However, multiparameter models based on synovial histopathology were relatively poor predictors of disease activity in individual patients. In conclusion, these data indicate that inflammatory infiltration of the synovium with CD163+ macrophages and PMNs as well as lining-layer hyperplasia reflect global disease activity in SpA, independently of the SpA subtype

Genomics, transcriptomics and proteomics to elucidate the pathogenesis of rheumatoid arthritis.

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Song, Xinqiang; Lin, Qingsong

2017-08-01

Rheumatoid arthritis is an autoimmune disease that affects several organs and tissues, predominantly the synovial joints. The pathogenesis of this disease is not completely understood, which maybe involved in the genomic variations, gene expression, protein translation and post-translational modifications. These system variations in genomics, transcriptomics and proteomics are dynamic in nature and their crosstalk is overwhelmingly complex, thus analyzing them separately may not be very informative. However, various '-omics' techniques developed in recent years have opened up new possibilities for clarifying disease pathways and thereby facilitating early diagnosis and specific therapies. This review examines how recent advances in the fields of genomics, transcriptomics and proteomics have contributed to our understanding of rheumatoid arthritis.

MRI-assessed therapeutic effects of locally administered PLGA nanoparticles loaded with anti-inflammatory siRNA in a murine arthritis model

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te Boekhorst, B.C.; Jensen, L.B.; Colombo, S.; Varkouhi, A.K.; Schiffelers, R.M.; Lammers, Twan Gerardus Gertudis Maria; Storm, Gerrit; Nielsen, H.M.; Strijkers, G.J.; Foged, C.; Nicolay, K.

2012-01-01

Abstract Rheumatoid arthritis is characterized by systemic inflammation of synovial joints leading to erosion and cartilage destruction. Although efficacious anti-tumor necrosis factor α (TNF-α) biologic therapies exist, there is an unmet medical need for safe and more efficient treatment regimens

Comparison between rheumatoid arthritis and osteoarthritis on knee joint MRI

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Wang Zhi; Meng Xianghong, Suo Yongmei; Wan Yeda

2013-01-01

Objective: To compare the MRI characteristics between the late stage rheumatoid arthritis (RA) and osteoarthritis (OA) in the knee joints. Materials and Methods: We collected knee joints MR data using 0.35 T MR from 40 patients with rheumatoid arthritis and 60 cases with osteoarthritis between July, 2010 and August, 2012. We compared the differences in the menisci, the articular cartilage, the subchondral bone, and synovial lesions between the two groups. We calculated the morbidity and analyzed the severity in each part in both groups, and compared the differences between the two groups. If P<0.05, the results had statistical significance. Results: The injury of all parts in the medial and lateral menisci in the RA group was more severe than in the OA group (P<0.05). The articular cartilage of lateral tibiofemoral joints in the RA group was more severe than in the OA group (Z values of the lateral femoral condyle and the lateral tibial plateau were 5.702 vs. 7.534, P<0.05). However, the injury did not significantly differ at the articular cartilage in the patellofemoral joints and in the medial tibiofemoral joints (P>0.05). The subchondral bone marrow lesions of both medial and lateral tibiofemoral joints in the RA group were more severe than in the OA group (the χ 2 values of the medial and lateral femoral condyle were 6.730 and 23.938, respectively; the χ 2 values of the medial and lateral tibial plateau were 12.033 and 41.017, respectively; P<0.05). However, there was no statistical significance in the subchondral bone marrow lesions in the patellofemoral joints (P>0.05). In the RA group, there were 97.5% (39/40) cases having diffuse synovial thickening, including 20 cases with bone destruction in the bare area. In the OA group, there were 21.7% (13/60) cases having synovial thickening with less extend compared to RA group, none of them had bone destruction in the bare area. Conclusions: There are diffuse synovial thickening, bare area destruction, diffuse

The joint in psoriatic arthritis.

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Mortezavi, Mahta; Thiele, Ralph; Ritchlin, Christopher

2015-01-01

Psoriatic arthritis (PsA), a chronic inflammatory joint disease associated with psoriasis, is notable for diversity in disease presentation, course and response to treatment. Equally varied are the types of musculoskeletal involvement which include peripheral and axial joint disease, dactylitis and enthesitis. In this review, we focus on the psoriatic joint and discuss pathways that underlie synovial, cartilage and bone inflammation and highlight key histopathologic features. The pivotal inflammatory mechanisms and pathobiology of PsA parallel findings in other forms of spondyloarthritis but are distinct from disease pathways described in rheumatoid synovitis and bone disease. The diagnosis of PsA from both a clinical and imaging perspective is also discussed.

Synovial Lipoma of the Subtalar Joint.

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Whitaker, Jeffrey M; Richards, Sarah; LeCastre, Michael J; Hooke, Thomas G

2017-07-01

Lipomas are benign adipose masses that are rarely associated with synovial membranes. In addition, there are only a few reports describing synovial lipomas in the foot. No reported occurrence of this lesion in the subtalar joint currently exists. This case report documents the presentation, clinical evaluation, advanced imaging, and surgical management of a 45-year-old man with a large synovial lipoma of the subtalar joint.

Influence of Angiotensin-Aldosterone System on Ultrasound of Joints in Patients with Rheumatoid Arthritis

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O.B. Komarova

2014-02-01

Full Text Available In patients with rheumatoid arthritis and high level of angiotensin II in the blood at ultrasound of joints there are often being detected effusion in the joint cavity, hypervascularization of synovium with 2–3 points and tenosynovitis characterizing inflammatory exudative processes. In patients with high level of aldosterone, hyperplasia of synovium, presence of pannus and bone and cartilage erosions, indicating proliferative-destructive processes, were predominated. Identified correlations show that with increasing levels of angiotensin II in the blood increases the intensity of the vascularization of the synovial membrane, joint effusion, and an increase in the concentration of aldosterone in the blood affects the synovial thickness indicators, the presence of pannus and bone erosions amount.

Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

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Giono Silvia

2002-06-01

Full Text Available Abstract Background Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints. Methods P-140 and PG-18 strains were each injected in the knee joints of 14 rabbits in order to evaluate and compare their arthritogenicity. P-140 was also injected in the trachea of 14 rabbits in order to test the ability of the bacteria to reach the joints and induce arthritis. Results M. fermentans produced an acute arthritis in rabbits. Joint swelling appeared first in rabbits injected with P-140, which caused a more severe arthritis than PG-18. Both strains were able to migrate to the uninoculated knee joints and they were detected viable in the joints all along the duration of the experiment. Changes in the synovial tissue were more severe by the end of the experiment and characterized by the infiltration of neutrophils and substitution of adipose tissue by connective tissue. Rabbits intracheally injected with P-140 showed induced arthritis and the bacteria could be isolated from lungs, blood, heart, kidney, spleen, brain and joints. Conclusion M. fermentans induced arthritis regardless of the inoculation route. These findings may help explain why mycoplasmas are commonly isolated from the joints of rheumatic patients.

The Impact of MicroRNA-223-3p on IL-17 Receptor D Expression in Synovial Cells.

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Nozomu Moriya

Full Text Available Rheumatoid arthritis (RA is an autoimmune inflammatory disease affecting joints. Elevated plasma levels of microRNA-223-3p (miR-223-3p in patients with RA are implicated in the pathogenesis of the disease. This study aimed to analyze the functional role of miR-223-3p in the pathogenesis of RA by overexpressing miR-223-3p in synovial cell lines.Arthritis was induced in the RA model of SKG mice by injection of ß-glucan. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Plasma levels of miRNA were determined by panel real-time PCR analysis. Target genes of the differentially expressed miRNAs in SKG mice were analyzed using miRNA target prediction algorithms. The dual-luciferase reporter system was used to evaluate the relationship between miR-223-3p and IL-17 receptor D (IL-17RD. The activity of miR-223-3p was analyzed by transfection of plasmid vectors overexpressing miR-223-3p into IL-17RD-expressing NIH3T3 and MH7A cell lines. Il6 and Il17rd mRNA expression was analyzed by quantitative real-time PCR. IL-17RD protein expression was analyzed by western blot analysis.We identified 17 upregulated miRNAs (fold change > 2.0 in plasma of SKG mice injected with ß-glucan relative to untreated SKG mice. Il17rd was identified as the candidate target gene of miR-223-3p using five miRNA target prediction algorithms. The transfection of plasmid vectors overexpressing miR-223-3p into NIH3T3 and MH7A cells resulted in the downregulation of Il17rd expression and upregulation of Il6 expression. Expression of miR-223-3p and Il6 mRNA in MH7A cells was upregulated; however, that of Il17rd mRNA was downregulated following TNF-α stimulation. IL-17RD expression in synovial tissues from SKG mice and RA patients was inversely correlated with the severity of arthritis.This study is the first to demonstrate that miR-223-3p downregulates IL-17RD in both mouse and human cells; miR-223-3p may contribute to

Primary renal synovial sarcoma

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Girish D. Bakhshi

2012-03-01

Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

Effects of RuPeng15 Powder (RPP15 on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats

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Y.-Y. Kou

2015-01-01

Full Text Available RuPeng15 Powder (RPP15 is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses antigout, anti-inflammatory, and antihyperuricemic properties based on the traditional conceptions. The present study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty arthritis induced by monosodium urate (MSU crystals. In the present study, we found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg in rats with gouty arthritis induced by MSU crystals significantly attenuated the knee swelling. Histomorphometric and immunohistochemistry analyses revealed that MSU-induced inflammatory cell infiltration and the elevated expressions of nuclear transcription factor-κB p65 (NF-κB p65 in synovial tissues were significantly inhibited, and enzyme-linked immunosorbent assay (ELISA result showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-α, interleukin-1 beta (IL-1β, and interleukin-8 (IL-8 in synovial fluid were reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg. We conclude that RPP15 may be a promising candidate for the development of a new treatment for gout and its activity of antigout may be partially related to inhibiting TNF-α, IL-1β, IL-8, and NF-κB p65 expression in the synovial tissues.

Tofacitinib restores the inhibition of reverse cholesterol transport induced by inflammation: understanding the lipid paradox associated with rheumatoid arthritis.

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Pérez-Baos, S; Barrasa, J I; Gratal, P; Larrañaga-Vera, A; Prieto-Potin, I; Herrero-Beaumont, G; Largo, R

2017-09-01

Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The JAK inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analysed the effect of tofacitinib on the lipid profile of hyperlipidaemic rabbits with chronic arthritis (CA) and on the changes in reverse cholesterol transport (RCT) during chronic inflammation. CA was induced in previously immunized rabbits, fed a high-fat diet, by administering four intra-articular injections of ovalbumin. A group of rabbits received tofacitinib (10 mg·kg -1 ·day -1 ) for 2 weeks. Systemic and synovial inflammation and lipid content were evaluated. For in vitro studies, THP-1-derived macrophages were exposed to high lipid concentrations and then stimulated with IFNγ in the presence or absence of tofacitinib in order to study mediators of RCT. Tofacitinib decreased systemic and synovial inflammation and increased circulating lipid levels. Although it did not modify synovial macrophage density, it reduced the lipid content within synovial macrophages. In foam macrophages in culture, IFNγ further stimulated intracellular lipid accumulation, while the JAK/STAT inhibition provoked by tofacitinib induced lipid release by increasing the levels of cellular liver X receptor α and ATP-binding cassette transporter (ABCA1) synthesis. Active inflammation could be associated with lipid accumulation within macrophages of CA rabbits. JAK inhibition induced lipid release through RCT activation, providing a plausible explanation for the effect of tofacitinib on the lipid profile of RA patients. © 2017 The British Pharmacological Society.

Lactobacillus salivarius Isolated from Patients with Rheumatoid Arthritis Suppresses Collagen-Induced Arthritis and Increases Treg Frequency in Mice.

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Liu, Xiaofei; Zhang, Juan; Zou, Qinghua; Zhong, Bing; Wang, Heng; Mou, Fangxiang; Wu, Like; Fang, Yongfei

2016-12-01

Previously, we demonstrated that Lactobacillus salivarius was more abundant in patients with rheumatoid arthritis (RA), an inflammatory autoimmune disease wherein the gut microbiota is altered, than in healthy individuals. However, the effect of L. salivarius in RA is unclear. Hence, we investigated the effect of L. salivarius isolated from patients with RA on collagen-induced arthritis (CIA) in mice. L. salivarius UCC118 or L. plantarum WCFS1 isolated from patients with RA was administered orally for 5 weeks, starting from 2 weeks before the induction of arthritis in DBA/1 mice. Clinical score progression, histological changes, serum cytokine concentrations, and the proportion of interleukin (IL)-17-producing T cells [T helper 17 (Th17)] and regulatory T cells (Tregs) in the spleen were evaluated. Bone erosion was evaluated by micro-computed tomography. CIA mice treated with either L. salivarius or L. plantarum showed lower arthritis scores, milder synovial infiltration, and less bone erosion when compared with phosphate-buffered, saline-treated CIA mice. Administration of L. salivarius and L. plantarum reduced the Th17 cell fraction and increased the Treg fraction. L. salivarius-treated CIA mice displayed a significant increase in serum anti-inflammatory IL-10 levels. Thus, pretreatment with L. salivarius could significantly improve CIA in mice and may help alleviate RA in a clinical setting.

Targeting IL-17 AND IL-17D receptors of rheumatoid arthritis using phytocompounds: A Molecular Docking study

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Thabitha, A.; Thoufic Ali, A. M. Mohamed; Shweta Kumari, Singh; Rakhi; Swami, Varsha; Mohana Priya, A.; Sajitha Lulu, S.

2017-11-01

Rheumatoid arthritis (RA) is a chronic autoimmune condition of the connective tissue in synovial joints, characterized by inflammation which can lead to bone and cartilage destruction. IL-17 and IL-17D cytokines produced by a number of cell types, primarily promote pro-inflammatory immune responses and negative regulator in fibroblast growth factor signalling. Thus, the promising therapeutic strategies focus on targeting these cytokines, which has led to the identification of effective inhibitors. However, several studies focused on identifying the anti-arthritic potential of natural compounds. Therefore, in the present study we undertook in silico investigations to decipher the anti-inflammatory prospective of phytocompounds by targeting IL-17 and IL-17D cytokines using Patch Dock algorithm. Additionally, IL-17 and IL-17D proteins structure were modelled and validated for molecular docking study. Further, phytocompounds based on anti-inflammatory property were subjected to Lipinski filter and ADMET properties indicated that all of these compounds showed desirable drug-like criteria. The outcome of this investigation sheds light on the anti-inflammatory mechanism of phytocompounds by targeting IL-17 and IL-D for effective treatment of RA.

Immunomodulation of Autoimmune Arthritis by Herbal CAM

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Shivaprasad H. Venkatesha

2011-01-01

Full Text Available Rheumatoid arthritis (RA is a debilitating autoimmune disease of global prevalence. The disease is characterized by synovial inflammation leading to cartilage and bone damage. Most of the conventional drugs used for the treatment of RA have severe adverse reactions and are quite expensive. Over the years, increasing proportion of patients with RA and other immune disorders are resorting to complementary and alternative medicine (CAM for their health needs. Natural plant products comprise one of the most popular CAM for inflammatory and immune disorders. These herbal CAM belong to diverse traditional systems of medicine, including traditional Chinese medicine, Kampo, and Ayurvedic medicine. In this paper, we have outlined the major immunological pathways involved in the induction and regulation of autoimmune arthritis and described various herbal CAM that can effectively modulate these immune pathways. Most of the information about the mechanisms of action of herbal products in the experimental models of RA is relevant to arthritis patients as well. The study of immunological pathways coupled with the emerging application of genomics and proteomics in CAM research is likely to provide novel insights into the mechanisms of action of different CAM modalities.

Changes in Ultrasonographic Vascularity Upon Initiation of Adalimumab Combination Therapy in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate.

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Kaeley, Gurjit S; Nishio, Midori J; Goyal, Janak R; MacCarter, Daryl K; Wells, Alvin F; Chen, Su; Kupper, Hartmut; Kalabic, Jasmina

2016-11-01

To assess joint disease activity by ultrasound (US) in patients with rheumatoid arthritis (RA) initiating treatment with adalimumab (ADA) plus methotrexate (MTX). Data for this post hoc analysis originated from the MUSICA trial (ClinicalTrials.gov identifier: NCT01185288), which evaluated the efficacy of initiating ADA (40 mg every other week) plus 7.5 or 20 mg/week MTX in 309 patients with RA with an inadequate response to MTX. Synovial vascularization over 24 weeks was assessed bilaterally at metacarpophalangeal joint 2 (MCP2), MCP3, MCP5, metatarsophalangeal joint 5, and the wrists by power Doppler US (PDUS). A semiquantitative 4-grade scale was used. Disease activity was assessed using the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and Simplified Disease Activity Index (SDAI). The correlation between continuous variables was assessed using Pearson's correlation coefficient. After 24 weeks of treatment with ADA plus MTX, rapid improvements in the mean synovial vascularity score were observed; the greatest improvements were in MCP2 (-0.5), MCP3 (-0.4), and the wrist (-0.4). At week 24, patients with the lowest DAS28-CRP ( 0.9). Synovial vascularity scores correlated poorly with DAS28, swollen joint count in 66 joints (SJC66), SJC28, tender joint count in 68 joints (TJC68), TJC28, Clinical Disease Activity Index (CDAI), SDAI, physician's global assessment, patient's global assessment of pain, and disease duration (ρ < 0.2). Thirty-two (70%) of 46 patients with a DAS28-CRP of <2.6, and 11 (58%) of 19 patients with an SDAI indicating remission had at least 1 joint with a synovial vascularity score of ≥1. PDUS detects changes in synovial vascularity in RA patients treated with ADA plus MTX, and residual synovial vascularity in patients in whom clinical disease control has been achieved. © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Angiography of histopathologic variants of synovial sarcoma

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Lois, J.F.; Fischer, H.J.; Mirra, J.M.; Gomes, A.S.; California Univ., Los Angeles

1986-01-01

Synovial sarcomas are rare soft tissue tumors which histopathologically can be divided into monophasic, biphasic and mixed variants. As part of a protocol for intra-arterial chemotherapy 12 patients with biopsy proven synovial sarcoma underwent angiography. The angiograms on these patients were reviewed to determine whether synovial sarcomas and their variants demonstrated a characteristic angiographic appearance. Synovial sarcomas appeared angiographically as soft tissue masses which showed a fine network of tumor vessels with an inhomogeneous capillary blush. Their degree of vascularity varied according to their histopathology. Monophasic synovial sarcomas demonstrated in general a higher degree of neovascularity than the biphasic form. This finding was also suggested by histopathologic analysis of the vessels in the tumor. Although angiography did not show a distinctive vascular pattern it may be useful to evaluate tumor size and vascularity. (orig.)

Contrast-enhanced power Doppler ultrasonography of the metacarpophalangeal joints in rheumatoid arthritis

DEFF Research Database (Denmark)

Szkudlarek, Marcin; Court-Payen, Michel; Strandberg, Charlotte

2003-01-01

The aim of this study was to examine, with dynamic contrast-enhanced MRI as the reference, if contrast-enhanced power Doppler ultrasonography (CE PDUS) of rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints provides additional information for evaluation of synovial inflammation compared...... with PDUS. One MCP joint in each of 15 RA patients and 3 healthy control persons were examined with PDUS before and after intravenous bolus Levovist contrast injection. Corresponding rates of early synovial enhancement (RESE), previously shown to be closely related to histopathological synovitis, were...... calculated from dynamic contrast-enhanced MR images obtained the same day. Prior to ultrasonography, the joint was evaluated clinically. Levovist increased the flow signal in 7 of 9 joints with pre-contrast flow-signal and in 0 of 9 without pre-contrast signal. No healthy controls showed CE PDUS signal...

Kaempferol inhibits the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes by blocking activation of the MAPK pathway.

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Pan, Dongmei; Li, Nan; Liu, Yanyan; Xu, Qiang; Liu, Qingping; You, Yanting; Wei, Zhenquan; Jiang, Yubao; Liu, Minying; Guo, Tianfeng; Cai, Xudong; Liu, Xiaobao; Wang, Qiang; Liu, Mingling; Lei, Xujie; Zhang, Mingying; Zhao, Xiaoshan; Lin, Changsong

2018-02-01

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) play an essential role in cartilage destruction. Aggressive migration and invasion by FLSs significantly affect RA pathology. Kaempferol has been shown to inhibit cancer cell migration and invasion. However, the effects of kaempferol on RA FLSs have not been investigated. Our study aimed to determine the effects of kaempferol on RA both in vitro and in vivo. In vitro, cell migration and invasion were measured using scratch assays and the Boyden chamber method, respectively. The cytoskeletal reorganization of RA FLSs was evaluated by immunofluorescence staining. Matrix metalloproteinase (MMP) levels were measured by real-time PCR, and protein expression levels were measured by western blotting. In vivo, the effects of kaempferol were evaluated in mice with CIA. The results showed that kaempferol reduced migration, invasion and MMP expression in RA FLSs. In addition, we demonstrated that kaempferol inhibited reorganization of the actin cytoskeleton during cell migration. Moreover, kaempferol dramatically suppressed tumor necrosis factor (TNF)-α-induced MAPK activation without affecting the expression of TNF-α receptors. We also demonstrated that kaempferol attenuated the severity of arthritis in mice with CIA. Taken together, these results suggested that kaempferol inhibits the migration and invasion of FLSs in RA by blocking MAPK pathway activation without affecting the expression of TNF-α receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

Cell-mediated immune response of synovial fluid lymphocytes to ureaplasma antigen in Reiter's syndrome

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Pavlica Ljiljana

2003-01-01

Full Text Available INTRODUCTION Reiter's syndrome (RS is an seronegative arthritis that occurs after urogenital or enteric infection which in addition with occular and/or mucocutaneous manifestations presents complete form of disease. According to previous understanding arthritis in the RS is the reactive one, which means that it is impossible to isolate its causative agent. However, there are the more and more authors suggesting that arthritis in the urogenital form of disease is caused by the infective agent in the affected joint. This suggestion is based on numerous studies on the presence of Chlmaydia trachomatis and Ureaplasma urealyticum in the inflamed joint by using new diagnostic methods in molecular biology published in the recent literature [1-3]. Besides, numerous studies of the humoral and cell-mediated immune response to "triggering" bacteria in the affected joint have supported previous suggestions [4-7]. Aim of the study was to determine whether synovial fluid T-cells specifically recognize the "triggering" bacteria presumably responsible for the Reiter's syndrome. METHOD The 3H-thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial fluid (SF and from peripheral blood (PB [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24 RS patients (24 PB samples, 9 SF samples and the results were compared with those found in 10 patients with rheumatoid arthritis (RA (10 PB samples, 5 SF samples. Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g for 40 minutes and than deposits carefully carried to other sterile glass tubes (Corex and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3 times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile 0.9% Na

Gadolinium-DTPA in rheumatoid arthritis and related diseases: First results with dynamic magnetic resonance imaging

International Nuclear Information System (INIS)

Reiser, M.F.; Bongartz, G.P.; Erlemann, R.; Sittek, H.; Peters, P.E.

1989-01-01

Thirty-four joints (19 knees, 15 wrists) of 31 patients suffering from rheumatoid arthritis and related disorders were examined prior to and following intravenous administration of Gadolinium-DTPA (0.1 mmol/kg body weight). T1-weighted spin-echo sequences and the gradient-echo technique FLASH were applied. FLASH scanning was used for the registration of the time-dependent changes of signal intensity following Gd-DTPA. Synovial proliferations exhibited a rapid and marked increase of signal intensity whereas fatty tissue, bone marrow, muscle and synovial effusion demonstrated only minor changes, causing enhanced contrast between synovial pannus and joint effusion or other neighbouring structures. Within the synovial pannus, ratios (absolute signal increase) of 131.3 ± 53.4% and 122.9 ± 51.1% were found in T1-weighted spin-echo and in FLASH sequences respectively. The average signal increase gradient of pannus (108.2 ± 70.6%/min) was significantly (p<0.001) different from muscle (13.4 ± 7.8%/min), fatty tissue (10.2 ± 8.4%/min), bone marrow (5.5 ± 7.1%/min), and joint effusion (14.7 ± 7.8%/min). (orig.)

Synovial sarcoma: MR evaluation in 23 patients

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Galant, J.; Marti-Bonmati, L.; Lafuente, J.; Hernandez, L.; Soler, R.; Saez, F.

1997-01-01

The synovial sarcoma is one of the most common soft tissue sarcomas. MR is the technique of choice to determine to local extension of malignant soft tissue tumors. To assess the clinical and MR imaging parameters associated with synovial sarcomas that aid in establishing their diagnosis. We review the clinical findings and images of 23 histologically confirmed synovial sarcomas that were studied by MR. Synovial sarcomas usually develop in young adults as soft tissue tumors, preferentially in the deep tissues of an extremity in close proximity to a joint. They are characterized as having a lobulated contour and septa, frequently infiltrating neighboring tissues at some point, and are heterogeneous. The presence of hemorrhage, as well as infiltration of the fascia in subcutaneous tumors, suggests the diagnosis of synovial sarcoma. The development of perilesional edema is not uncommon. Although, logically, the clinical and radiological features of synovial sarcomas can overlap with those of other soft tissue tumors, the findings described here are fairly characteristic of these lesions: thus, when present, they should serve to orient the diagnostic process. (Author) 16 refs

Total glucosides of paeony inhibit the proliferation of fibroblast-like synoviocytes through the regulation of G proteins in rats with collagen-induced arthritis.

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Jia, Xiao-Yi; Chang, Yan; Sun, Xiao-Jing; Wu, Hua-Xun; Wang, Chun; Xu, Hong-Mei; Zhang, Lei; Zhang, Ling-Ling; Zheng, Yong-Qiu; Song, Li-Hua; Wei, Wei

2014-01-01

The aim of this study was to investigate the expression of G proteins in fibroblast-like synoviocytes (FLSs) from rats with collagen-induced arthritis (CIA) and to determine the effect of total glucosides of paeony (TGP). CIA rats were induced with chicken type II collagen (CCII) in Freund's complete adjuvant. The rats with experimental arthritis were randomly separated into five groups and then treated with TGP (25, 50, and 100mg/kg) from days 14 to 35 after immunization. The secondary inflammatory reactions were evaluated through the polyarthritis index and histopathological changes. The level of cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The FLS proliferation response was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The toxin-catalyzed ADP-ribosylation of G proteins was performed through autoradiography. The results show that TGP (25, 50, and 100mg/kg) significantly decreased the arthritis scores of CIA rats and improved the histopathological changes. TGP inhibited the proliferation of FLSs and increased the level of cAMP. Moreover, the FLS proliferation and the level of Gαi expression were significantly increased, but the level of Gαs expression was decreased after stimulation with IL-1β (10ng/ml) in vitro. TGP (12.5 and 62.5μg/ml) significantly inhibited the FLS proliferation and regulated the balance between Gαi and Gαs. These results demonstrate that TGP may exert its anti-inflammatory effects through the suppression of FLS proliferation, which may be associated with its ability to regulate the balance of G proteins. Thus, TGP may have potential as a therapeutic agent for the treatment of rheumatoid arthritis. © 2013.

Hypoxia induces mitochondrial mutagenesis and dysfunction in inflammatory arthritis.

LENUS (Irish Health Repository)

Biniecka, Monika

2012-02-01

OBJECTIVE: To assess the levels and spectrum of mitochondrial DNA (mtDNA) point mutations in synovial tissue from patients with inflammatory arthritis in relation to in vivo hypoxia and oxidative stress levels. METHODS: Random Mutation Capture assay was used to quantitatively evaluate alterations of the synovial mitochondrial genome. In vivo tissue oxygen levels (tPO(2)) were measured at arthroscopy using a Licox probe. Synovial expression of lipid peroxidation (4-hydroxynonenal [4-HNE]) and mitochondrial cytochrome c oxidase subunit II (CytcO II) deficiency were assessed by immunohistochemistry. In vitro levels of mtDNA point mutations, reactive oxygen species (ROS), mitochondrial membrane potential, and markers of oxidative DNA damage (8-oxo-7,8-dihydro-2\\'-deoxyguanine [8-oxodG]) and lipid peroxidation (4-HNE) were determined in human synoviocytes under normoxia and hypoxia (1%) in the presence or absence of superoxide dismutase (SOD) or N-acetylcysteine (NAC) or a hydroxylase inhibitor (dimethyloxalylglycine [DMOG]). Patients were categorized according to their in vivo tPO(2) level (<20 mm Hg or >20 mm Hg), and mtDNA point mutations, immunochemistry features, and stress markers were compared between groups. RESULTS: The median tPO(2) level in synovial tissue indicated significant hypoxia (25.47 mm Hg). Higher frequency of mtDNA mutations was associated with reduced in vivo oxygen tension (P = 0.05) and with higher synovial 4-HNE cytoplasmic expression (P = 0.04). Synovial expression of CytcO II correlated with in vivo tPO(2) levels (P = 0.03), and levels were lower in patients with tPO(2) <20 mm Hg (P < 0.05). In vitro levels of mtDNA mutations, ROS, mitochondrial membrane potential, 8-oxo-dG, and 4-HNE were higher in synoviocytes exposed to 1% hypoxia (P < 0.05); all of these increased levels were rescued by SOD and DMOG and, with the exception of ROS, by NAC. CONCLUSION: These findings demonstrate that hypoxia-induced mitochondrial dysfunction drives

Synovial chondromatosis of the knee

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Haanraadts, E.J. [Dept. of Radiology, Onze Lieve Vrouwe Gasthuis, Amsterdam (Netherlands); Taconis, W.K. [Dept. of Radiology, Onze Lieve Vrouwe Gasthuis, Amsterdam (Netherlands); Huib, J.; Hout, W. van den [Dept. of Radiology, University Hospital, Utrecht (Netherlands); Feldberg, M.A.M. [Dept. of Radiology, University Hospital, Utrecht (Netherlands)

1992-02-01

A case of synovial chondromatosis with extensive modern cross-sectional imaging ``workup`` is presented. The case is of interest because it shows in plain films the natural development of the osteo-cartilaginous bodies in an 8-year period. Computed tomography and magnetic resonance imaging are only of relative value in the diagnosis of synovial chondromatosis. However, both modalities have a superior efficacy in differentiating synovial chondromatosis from other entities: the joint capsule can be seen, a quantitative definition of the density of the soft tissue mass and the loose bodies is possible, which can be a key feature of diagnosis. Secondary bone erosion can be differentiated from destruction. (orig.)

Liquid crystals in biotribology synovial joint treatment

CERN Document Server

Ermakov, Sergey; Eismont, Oleg; Nikolaev, Vladimir

2016-01-01

This book summarizes the theoretical and experimental studies confirming the concept of the liquid-crystalline nature of boundary lubrication in synovial joints. It is shown that cholesteric liquid crystals in the synovial liquid play a significant role in the mechanism of intra-articular friction reduction. The results of structural, rheological and tribological research of the creation of artificial synovial liquids - containing cholesteric liquid crystals in natural synovial liquids - are described. These liquid crystals reproduce the lubrication properties of natural synovia and provide a high chondroprotective efficiency. They were tested in osteoarthritis models and in clinical practice.

The significance of 3H-thymidine degradation in cell culture experiments with special reference to rheumatoid arthritis

International Nuclear Information System (INIS)

Nykaenen, P.J.; Raunio, P.V.; Kankaanpaeae, P.U.

1988-01-01

The degradation of 3 H-thymidine under various cell culture conditions was analysed. It was found that a half of 3 H-thymidine was degraded to 3 H-thymine during 24 hours in PHA stimulation of blood lymphocytes. A control culture in which PHA was not added also caused 3 H-thymidine degradation. 3 H-thymidine degradation was prevented by adding 5-nitrouracil to the incubation medium at a concentration of 0.577 mg/ml. At the same time 5-NU increased 3 H-thymidine incorporation into lymphocytes by 47%. 5-NU also eliminated the inhibitory effect of rheumatoid arthritis synovial tissue eluate on PHA stimulation. In addition 5-NU and nonradioactive thymine increased the 3 H-thymidine labelling index of fresh rheumatoid arthritis synovial membrane biopsies, and also more of the isotope was accumulated in the individual cells of the membrane. These studies demonstrate that 3 H-thymidine degradation is an important phenomenon in cell cultures and that it can be prevented effectively by using 5-nitrouracil with 3 H-thymidine. (author)

Some historical remarks on microcrystalline arthritis (gout and chondrocalcinosis

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G. Pasero

2012-01-01

Full Text Available The history of microcrystalline arthritis only began in 1961 when Daniel McCarty and Joseph Lee Hollander demonstrated the presence of sodium monourate crystals in the synovial fluid of gouty patients. However, gout is a historical disease, thanks to the descriptions of Hippocrates, Caelius Aurelianus, Soranus of Ephesus and Araeteus of Cappadocia. The relationship between hyperuricemia and gout was first documented in the nineteenth century by Alfred Baring Garrod, who demonstrated deposits of uric acid crystals on a linen thread held dipped in acidified blood (the so-called “thread method”. Gout has always been considered a prerogative of the moneyed classes (arthritis divitum, and history is full of famous gouty personalities, including kings, emperors, popes, commanders, politicians, artists, writers, philosophers and scientists. Another form of microcrystalline arthritis, chondrocalcinosis, was identified as being a rheumatic disorder different from gout in the 1960s. As a specific clinical entity, it was first identified in 1958 by Dušan Žitnˇan and Štefan Sit’aj in a few Slovak families.

The many shades of enhancement: timing of post-gadolinium images strongly influences the scoring of juvenile idiopathic arthritis wrist involvement on MRI

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Rieter, Jasper F.M.M.; Nusman, Charlotte M.; Hemke, Robert; Maas, Mario [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); Tanturri de Horatio, Laura [Ospedale Pediatrico Bambino Gesu, Department of Radiology, Rome (Italy); Ording Mueller, Lil-Sofie [Oslo University Hospital, Department of Radiology, Oslo (Norway); Avenarius, Derk F.M. [Faculty of Health Sciences at the University of Tromsoe, Tromsoe (Norway); Rossum, Marion A.J. van [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); Emma Children' s Hospital, Amsterdam (Netherlands); Malattia, Clara [Ospedale Pediatrico Gaslini, Department of Paediatrics, Genoa (Italy); Rosendahl, Karen [Haukeland University Hospital, Radiology Department, Section of Pediatric Radiology, Bergen (Norway); University of Bergen, Department of Clinical Medicine, K1, Bergen (Norway)

2016-10-15

Potential long-term side effects of treatment for juvenile idiopathic arthritis are concerning. This has necessitated accurate tools, such as MRI, to monitor treatment response and allow for personalized therapy. To examine the extent to which timing of post-contrast MR images influences the scoring of inflammatory change in the wrist in children with juvenile idiopathic arthritis. We studied two sets of post-contrast 3-D gradient echo MRI series of the wrist in 34 children with juvenile idiopathic arthritis. These images were obtained immediately after administration of intravenous contrast material and again after approximately 10 min. The dataset was drawn from a prospective multicenter project conducted 2006-2010. We assessed five wrist locations for synovial enhancement, effusion and overall inflammation. Examinations were scored by one radiologist in two sessions - the first was based on the early post-contrast images, and the later session, for which the previous findings were masked, was based on the later post-contrast images. Fifty-two of the 170 locations (30.6%) received a higher synovial enhancement score based on the late post-contrast images as compared to the early images. Sixty of the 170 (35%) locations received a higher total inflammation score. The mean scores of synovial enhancement and total inflammation were significantly higher when based on the late post-contrast images as compared to the early post-contrast images. An MRI-based scoring system for the presence and degree of synovitis should be based on a standardized MR-protocol with a fixed interval between intravenous contrast injection and post-contrast images. (orig.)

Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

Science.gov (United States)

2016-01-01

ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

Synovial chondrosarcoma: Report of two cases and literature review

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Zamora, E.E. [Department of Orthopaedic Surgery, Hospital Dr. R.A Calderon Guardia, Universidad De Costa Rica, P.O. Box 628-3000, Heredia (Costa Rica); Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Mansor, A. [Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Department of Orthopaedic Surgery, University of Malaya, Kuala Lumpur 59100 (Malaysia); Vanel, D. [Musculoskeletal Oncology Research Center, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy)], E-mail: dvanel@ior.it; Errani, C.; Mercuri, M. [Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Picci, P. [Musculoskeletal Oncology Research Center, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy); Alberghini, M. [Musculoskeletal Anatomical Pathology Department, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy)

2009-10-15

Synovial chondrosarcoma is a rare soft tissue tumor that can arise from a previous synovial chondromatosis or as de novo tumor. The clinical and radiological findings of this malignancy are very similar to those of aggressive synovial chondromatosis. Confusion with other joint pathologies makes the diagnosis of synovial chondrosarcoma difficult in most of the cases. We present one recently diagnosed and treated case of synovial chondrosarcoma. The review of our hospital database revealed one more similar case. In both cases the malignancy arose from a pre-existing synovial chondromatosis. We also present a literature review emphasizing the clinical and histological findings of this rare entity.

Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

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Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

2008-11-15

We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

Induction of lyme arthritis in LSH hamsters

International Nuclear Information System (INIS)

Schmitz, J.L.; Schell, R.F.; Hejka, A.; England, D.M.; Konick, L.

1988-01-01

In studies of experimental Lyme disease, a major obstacle has been the unavailability of a suitable animal model. We found that irradiated LSH/Ss Lak hamsters developed arthritis after injection of Borrelia burgdorferi in the hind paws. When nonirradiated hamsters were injected in the hind paws with B. burgdorferi, acute transient synovitis was present. A diffuse neutrophilic infiltrate involved the synovia and periarticular structures. The inflammation was associated with edema, hyperemia, and granulation tissue. Numerous spirochetes were seen in the synovial and subsynovial tissues. The histopathologic changes were enhanced in irradiated hamsters. The onset and duration of the induced swelling were dependent on the dose of radiation and the inoculum of spirochetes. Inoculation of irradiated hamsters with Formalin-killed spirochetes or medium in which B. burgdorferi had grown for 7 days failed to induce swelling. This animal model should prove useful for studies of the immune response to B. burgdorferi and the pathogenesis of Lyme arthritis

Dynamic contrast-enhanced imaging of the wrist in rheumatoid arthritis: dedicated low-field (0.25-T) versus high-field (3.0-T) MRI

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Lee, Ryan K.L.; Griffith, James F.; Wang, D.F.; Yeung, David K.W. [The Chinese University of Hong Kong, Department of Imaging and Interventional Radiology, Prince Of Wales Hospital, Hong Kong, SAR (China); Shi, L. [The Chinese University of Hong Kong, Department of Medicine and Therapeutics, Division of Neurology, Hong Kong, SAR (China); Li, Edmund K.; Tam, L.S. [The Chinese University of Hong Kong, Department of Medicine, Division of Rheumatology, Prince Of Wales Hospital, Hong Kong, SAR (China)

2015-08-15

To compare the assessment of wrist synovitis severity, synovial volume and synovial perfusion parameters on a dedicated low-field (0.25-T) to that of a high-field (3-T) whole-body MR system in patients with rheumatoid arthritis (RA). Twenty-one patients (mean age 50.0 ± 9.8 years) with active RA were recruited prospectively. Dynamic contrast-enhanced MRI examination of the most severely affected wrist was performed at both 0.25 T and 3 T. Three MRI-derived parameters, synovitis severity (RAMRIS grade), synovial volume (ml{sup 3}) and synovial perfusion indices (maximum enhancement and enhancement slope), were compared. Comparing 0.25- and 3-T MRI, there was excellent agreement for semiquantitative assessment (r: 0.80, p < 0.00001) of synovitis (RAMRIS) as well as quantitative assessment (r: 0.94, p < 0.00001) of synovial volume. Good agreement for synovial Emax (r: 0.6, p = 0.002) and fair agreement (r: 0.5, p = 0.02) for synovial Eslope was found. Imaging of the RA wrist at 0.25 T yields excellent correlation with 3 T with regard to the synovitis activity score (RAMRIS) and synovial volume measurement. Fair to good correlation between low- (0.25-T) and high-field (3-T) MR systems was found for perfusion parameters, being better for Emax than for Eslope. (orig.)

The effects of arctigenin on human rheumatoid arthritis fibroblast-like synoviocytes.

Science.gov (United States)

Liu, Hongbin; Yang, Yang; Cai, Xiaosong; Gao, Yunlong; Du, Jun; Chen, Shuo

2015-08-01

Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) play an important role in the initiation and progression of RA, which are resistant to apoptosis and proliferate in an anchorage-independent manner. The effects of arctigenin on the proliferation and apoptosis of RAFLSs were explored. Arctigenin (0-160 µM) was used to treat RAFLSs for 48 h. Cell viability and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining. Western blot analysis was performed to detect the changes in apoptosis-related genes. Arctigenin decreased cell viability by 23, 30, and 38% at the dose of 10, 20, and 30 µM, respectively. The half maximal inhibitory concentration (IC50) of arctignein on RAFLSs was about 38 µM. Moreover, 9, 15, and 21% of RAFLSs are induced apoptosis by 10, 20, and 30 µM of arctigenin. The apoptotic response was due to the loss of mitochondrial membrane potential, coupled with the release of cytochrome C into cytoplasm, the up-regulation of pro-apoptotic protein, Bax, and down-regulation of antiapoptotic protein, B cell lymphoma 2 (Bcl-2). The activation of mitochondrial pathway in arctigenin-treated RAFLSs induced the cleavage of caspase-9, caspase-3, and poly (ADP-ribose) polymerase (PARP). Additionally, arctigenin inhibited the nuclear translocation of p65, decreased the degradation of inhibitor of kappa B alpha (IκBα), and attenuated the phosphorylation of Akt. Our results reveal that arctigenin inhibits cell proliferation and induces mitochondrial apoptosis of RAFLSs, which is associated with the modulation of NF-κB and Akt signaling pathways.

Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model

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Seiji Shimomura

2018-06-01

Full Text Available We analyzed the influence of treadmill running on rheumatoid arthritis (RA joints using a collagen-induced arthritis (CIA rat model. Eight-week-old male Dark Agouti rats were randomly divided into four groups: The control group, treadmill group (30 min/day for 4 weeks from 10-weeks-old, CIA group (induced CIA at 8-weeks-old, and CIA + treadmill group. Destruction of the ankle joint was evaluated by histological analyses. Morphological changes of subchondral bone were analyzed by μ-CT. CIA treatment-induced synovial membrane invasion, articular cartilage destruction, and bone erosion. Treadmill running improved these changes. The synovial membrane in CIA rats produced a large amount of tumor necrosis factor-α and Connexin 43; production was significantly suppressed by treadmill running. On μ-CT of the talus, bone volume fraction (BV/TV was significantly decreased in the CIA group. Marrow star volume (MSV, an index of bone loss, was significantly increased. These changes were significantly improved by treadmill running. Bone destruction in the talus was significantly increased with CIA and was suppressed by treadmill running. On tartrate-resistant acid phosphate and alkaline phosphatase (TRAP/ALP staining, the number of osteoclasts around the pannus was decreased by treadmill running. These findings indicate that treadmill running in CIA rats inhibited synovial hyperplasia and joint destruction.

Intraneural synovial sarcoma of the median nerve

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Rahul Kasukurthi

2010-06-01

Full Text Available Synovial sarcomas are soft-tissue malignancies with a poor prognosis and propensity for distant metastases. Although originally believed to arise from the synovium, these tumors have been found to occur anywhere in the body. We report a rare case of synovial sarcoma arising from the median nerve. To our knowledge, this is the twelfth reported case of intraneural synovial sarcoma, and only the fourth arising from the median nerve. Because the diagnosis may not be apparent until after pathological examination of the surgical speci­men, synovial sarcoma should be kept in mind when dealing with what may seem like a benign nerve tumor.

Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes.

Science.gov (United States)

Kloesch, Burkhard; Becker, Tatjana; Dietersdorfer, Elisabeth; Kiener, Hans; Steiner, Guenter

2013-02-01

It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA). MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and -7 was checked with specific antibodies. Curcumin effectively blocked IL-1β and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1β. Furthermore, curcumin inhibited activation of NF-κB and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis. The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantitative imaging by pixel-based contrast-enhanced ultrasound reveals a linear relationship between synovial vascular perfusion and the recruitment of pathogenic IL-17A-F+IL-23+ CD161+ CD4+ T helper cells in psoriatic arthritis joints.

Science.gov (United States)

Fiocco, Ugo; Stramare, Roberto; Martini, Veronica; Coran, Alessandro; Caso, Francesco; Costa, Luisa; Felicetti, Mara; Rizzo, Gaia; Tonietto, Matteo; Scanu, Anna; Oliviero, Francesca; Raffeiner, Bernd; Vezzù, Maristella; Lunardi, Francesca; Scarpa, Raffaele; Sacerdoti, David; Rubaltelli, Leopoldo; Punzi, Leonardo; Doria, Andrea; Grisan, Enrico

2017-02-01

To develop quantitative imaging biomarkers of synovial tissue perfusion by pixel-based contrast-enhanced ultrasound (CEUS), we studied the relationship between CEUS synovial vascular perfusion and the frequencies of pathogenic T helper (Th)-17 cells in psoriatic arthritis (PsA) joints. Eight consecutive patients with PsA were enrolled in this study. Gray scale CEUS evaluation was performed on the same joint immediately after joint aspiration, by automatic assessment perfusion data, using a new quantification approach of pixel-based analysis and the gamma-variate model. The set of perfusional parameters considered by the time intensity curve includes the maximum value (peak) of the signal intensity curve, the blood volume index or area under the curve, (BVI, AUC) and the contrast mean transit time (MTT). The direct ex vivo analysis of the frequencies of SF IL17A-F + CD161 + IL23 + CD4 + T cells subsets were quantified by fluorescence-activated cell sorter (FACS). In cross-sectional analyses, when tested for multiple comparison setting, a false discovery rate at 10%, a common pattern of correlations between CEUS Peak, AUC (BVI) and MTT parameters with the IL17A-F + IL23 + - IL17A-F + CD161 + - and IL17A-F + CD161 + IL23 + CD4 + T cells subsets, as well as lack of correlation between both peak and AUC values and both CD4 + T and CD4 + IL23 + T cells, was observed. The pixel-based CEUS assessment is a truly measure synovial inflammation, as a useful tool to develop quantitative imaging biomarker for monitoring target therapeutics in PsA.

Association of Increased F4/80high Macrophages With Suppression of Serum-Transfer Arthritis in Mice With Reduced FLIP in Myeloid Cells.

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Huang, Qi-Quan; Birkett, Robert; Doyle, Renee E; Haines, G Kenneth; Perlman, Harris; Shi, Bo; Homan, Philip; Xing, Lianping; Pope, Richard M

2017-09-01

Macrophages are critical in the pathogenesis of rheumatoid arthritis (RA). We recently demonstrated that FLIP is necessary for the differentiation and/or survival of macrophages. We also showed that FLIP is highly expressed in RA synovial macrophages. This study was undertaken to determine if a reduction in FLIP in mouse macrophages reduces synovial tissue macrophages and ameliorates serum-transfer arthritis. Mice with Flip deleted in myeloid cells (Flip f/f LysM c/+ mice) and littermate controls were used. Arthritis was induced by intraperitoneal injection of K/BxN serum. Disease severity was evaluated by clinical score and change in ankle thickness, and joints were examined by histology and immunohistochemistry. Cells were isolated from the ankles and bone marrow of the mice and examined by flow cytometry, real-time quantitative reverse transcriptase-polymerase chain reaction, or Western blotting. In contrast to expectations, Flip f/f LysM c/+ mice developed more severe arthritis early in the clinical course, but peak arthritis was attenuated and the resolution phase more complete than in control mice. Prior to the induction of serum-transfer arthritis, the number of tissue-resident macrophages was reduced. On day 9 after arthritis induction, the number of F4/80 high macrophages in the joints of the Flip f/f LysM c/+ mice was not decreased, but increased. FLIP was reduced in the F4/80 high macrophages in the ankles of the Flip f/f LysM c/+ mice, while F4/80 high macrophages expressed an antiinflammatory phenotype in both the Flip f/f LysM c/+ and control mice. Our observations suggest that reducing FLIP in macrophages by increasing the number of antiinflammatory macrophages may be an effective therapeutic approach to suppress inflammation, depending on the disease stage. © 2017, American College of Rheumatology.

Case report 460: Synovial chondrosarcoma of left knee

International Nuclear Information System (INIS)

Manivel, J.C.; Dehner, L.P.; Thompson, R.

1988-01-01

The case is presented of a 50-year-old man who presented with a mass around the left knee which radiologically was calcified heavily and eroded bone. A final diagnosis over a period of time of synovial chondrosarcoma was established. A description in depth of the types of synovial chondromatosis and the possible etiology of synovial chondrosarcoma was included in the manuscript. The diagnostic (radiological and pathological) features of the entity were described and the rarity of synovial chondrosarcoma was emphasized. (orig.)

Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis

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XU, WEI; HUANG, MINGQING; ZHANG, YUQIN; LI, HUANG; ZHENG, HAIYIN; YU, LISHUANG; CHU, KEDAN; LIN, YU; CHEN, LIDIAN

2016-01-01

Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)-6, IL-8, tumor necrosis factor-α and nuclear factor-κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription-polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE-treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action. PMID:27035125

Neutrophil Microvesicles from Healthy Control and Rheumatoid Arthritis Patients Prevent the Inflammatory Activation of Macrophages

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Hefin I. Rhys

2018-03-01

Full Text Available Microvesicles (MVs are emerging as a novel means to enact cell-to-cell communication in inflammation. Here, we aimed to ascertain the ability of neutrophil-derived MVs to modulate target cell behaviour, the focus being the macrophage.MVs were generated in response to tumour necrosis factor-α, from healthy control neutrophils or those from rheumatoid arthritis patients. MVs were used to stimulate human monocyte-derived macrophages in vitro, or administered intra-articularly in the K/BxN mouse model of arthritis. A macrophage/fibroblast-like synoviocyte co-culture system was used to study the effects of vesicles on the crosstalk between these cells.We demonstrate a direct role for phosphatidylserine and annexin-A1 exposed by the MVs to counteract classical activation of the macrophages, and promote the release of transforming growth factor-β, respectively. Classically-activated macrophages exposed to neutrophil MVs no longer activated fibroblast-like synoviocytes in subsequent co-culture settings. Finally, intra-articular administration of neutrophil MVs from rheumatoid arthritis patients in arthritic mice affected the phenotype of joint macrophages.Altogether these data, with the identification of specific MV determinants, open new opportunities to modulate on-going inflammation in the synovia – mainly by affecting macrophage polarization and potentially also fibroblast-like synoviocytes - through the delivery of autologous or heterologous MVs produced from neutrophils. Keywords: Neutrophils, Macrophages, Vesicles, Rheumatoid arthritis

Transforming growth factor (TGF)-β signalling is increased in rheumatoid synovium but TGF-β blockade does not modify experimental arthritis.

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Gonzalo-Gil, E; Criado, G; Santiago, B; Dotor, J; Pablos, J L; Galindo, M

2013-11-01

The aim of this study was to analyse the distribution of regulatory and inhibitory mothers against decapentaplegic homologue (Smad) proteins as markers of active transforming growth factor (TGF)-β signalling in rheumatoid arthritis (RA) synovial tissue and to investigate the effect of TGF-β blockade in the development and progression of collagen-induced arthritis. The expression of Smad proteins in synovial tissues from RA, osteoarthritic and healthy controls was analysed by immunohistochemistry. Arthritis was induced in DBA/1 mice by immunization with chicken type-II collagen (CII). TGF-β was blocked in vivo with the specific peptide p17 starting at the time of immunization or on the day of arthritis onset. T cell population frequencies and specific responses to CII were analysed. The expression of cytokines and transcription factors was quantified in spleen and joint samples. Statistical differences between groups were compared using the Mann-Whitney U-test or one-way analysis of variance (anova) using the Kruskal-Wallis test. p-Smad-2/3 and inhibitory Smad-7 expression were detected in RA and control tissues. In RA, most lymphoid infiltrating cells showed nuclear p-Smad-2/3 without Smad-7 expression. Treatment with TGF-β antagonist did not affect clinical severity, joint inflammation and cartilage damage in collagen-induced arthritis. Frequency of T cell subsets, mRNA levels of cytokines and transcription factors, specific proliferation to CII, serum interleukin (IL)-6 and anti-CII antibodies were comparable in p17 and phosphate-buffered saline (PBS)-treated groups. The pattern of Smad proteins expression demonstrates active TGF-β signalling in RA synovium. However, specific TGF-β blockade does not have a significant effect in the mice model of collagen-induced arthritis. © 2013 British Society for Immunology.

The visualization of pannus in rheumatoid arthritis using NMR imaging

International Nuclear Information System (INIS)

Schnarkowski, P.; Bader, C.; Goldmann, A.; Friedrich, J.M.

1992-01-01

The knee joints of 15 patients afflicted with rheumatoid arthritis were investigated using the method of nmr imaging. Parameters of investigation were the spin-echo and fast-field-echo sequences as well as the MR signal behaviour of proliferative synovial changes following intravenous administration of gadolinium dtpa. Pannus having formed on the articular surfaces or beneath the articular cartilages was distinguishable from other changes on the basis of the increased signal intensities to be observed after gadolinium dtpa had been given. (orig./GD) [de

Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages

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Sanjima Pal

2016-06-01

Full Text Available Any chronic, inflammatory, autoimmune disease (e.g. arthritis associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I–IV induced auto-reactive M1 type monocyte/macrophage model.

Diagnostic imaging of psoriatic arthritis. Part I: etiopathogenesis, classifications and radiographic features

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Iwona Sudoł-Szopińska

2016-03-01

Full Text Available Psoriatic arthritis is one of the spondyloarthritis. It is a disease of clinical heterogenicity, which may affect peripheral joints, as well as axial spine, with presence of inflammatory lesions in soft tissue, in a form of dactylitis and enthesopathy. Plain radiography remains the basic imaging modality for PsA diagnosis, although early inflammatory changes affecting soft tissue and bone marrow cannot be detected with its use, or the image is indistinctive. Typical radiographic features of PsA occur in an advanced disease, mainly within the synovial joints, but also in fibrocartilaginous joints, such as sacroiliac joints, and additionally in entheses of tendons and ligaments. Moll and Wright classified PsA into 5 subtypes: asymmetric oligoarthritis, symmetric polyarthritis, arthritis mutilans, distal interphalangeal arthritis of the hands and feet and spinal column involvement. In this part of the paper we discuss radiographic features of the disease. The next one will address magnetic resonance imaging and ultrasonography.

A model of Staphylococcus aureus bacteremia, septic arthritis, and osteomyelitis in chickens.

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Daum, R S; Davis, W H; Farris, K B; Campeau, R J; Mulvihill, D M; Shane, S M

1990-11-01

We studied the occurrence, magnitude, and kinetics of bacteremia and the resultant osteomyelitis and septic arthritis in an avian model of Staphylococcus aureus infection. Thirty-day-old male broiler chicks were inoculated i.v. with 10(5), 10(6), or 10(7) cfu of strain Duntravis, a beta-hemolytic, coagulase-producing, capsular type 8 isolate from the synovial fluid of a 2-year-old black boy. Bacteremia occurred in 80%, 90%, and 100% of animals inoculated with 10(5), 10(6), or 10(7) cfu, respectively. The magnitude of bacteremia in surviving, bacteremic animals increased for 96 hours after inoculation and then decreased after a plateau phase. Osteomyelitis and septic arthritis occurred only in chicks that were continuously bacteremic. The occurrence of osteomyelitis was uniform among continuously bacteremic animals and developed 1 to 23 hours after inoculation. Chickens are susceptible to systemic infections with S. aureus. Bacteremia, osteomyelitis, and septic arthritis may be induced in healthy chickens without prior manipulations that depress their resistance.

Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis

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Lucie Andrés Cerezo

2015-01-01

Full Text Available Objective. Progranulin (PGRN is implicated in the pathogenesis of rheumatoid arthritis (RA. The aim of this study was to assess the relationship between PGRN and disease activity in RA. Methods. PGRN levels were evaluated in patients with RA (n=47 and OA (n=42 and healthy controls (n=41. Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP, disease activity score (DAS28-CRP, and health assessment questionnaire (HAQ was studied. Results. Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1±100.2 and 221.5±102.5 versus 128.1±34.7 ng/mL; P<0.001. Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5±275.3 versus 241.4±165.2 ng/mL; P=0.002. PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r=0.327, P=0.049 and HAQ score (r=0.323, P=0.032, while synovial fluid PGRN correlated only with HAQ (r=0.310, P=0.043 in patients with RA. PGRN levels were not associated with CRP or autoantibodies. Conclusions. This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA.

Examination of in vivo gelatinolytic activity in rheumatoid arthritis synovial tissue using newly developed in situ zymography and image analyzer.

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Yoshida, W; Uzuki, M; Nishida, J; Shimamura, T; Sawai, T

2009-01-01

The aim of this study was to examine in vivo gelatinolytic activity of rheumatoid arthritis (RA) synovium using a newly developed in situ zymography (ISZ) method and pathological image analyzer, and to evaluate the relationship between this activity and several features on RA. A total of 8 samples of synovium were obtained from RA patients during surgery, and 8 samples from osteoarthritis (OA) patients were examined as controls. Furthermore, total 14 samples of syovium were obtained for comparison among radiographical classifications as Larsen grade (4 cases of grade III, 5 cases of grade IV and 5 cases of grade V). These specimens were frozen with OCT compound immediately after surgery. Frozen sections were applied to a newly developed gelatin-coated FIZ film (Fuji Film Co.Tokyo.Japan) designed for use ISZ, and incubated at 37 degrees C for 6 hours. Using an image analyzer (image processor for analytical pathology; IPAP), two variables were measured as indicators of in vivo gelatynolytic activity: optical density of gelatinolyzed area (ODG), and ratio of gelatinolyzed area (RGA). Also, we investigated the relationship between these indicators and the following variables: radiographic changes (Larsen grades), clinical data (C-reactive protein concentration), histological score of synovial tissue (modified Rooney's score), and expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 (assessed by immunohistochemistry). RA synovium had significantly higher RGA and lower ODG than OA, indicating higher gelatinolytic activity in RA. Synovium from cases with Larsen grade IV or V had significantly lower ODG than cases with grade III, but there was no significant difference in RGA between grades. There was no significant correlation between gelatinolytic activity (ODG or RGA) and either CRP or modified Rooney's Histological Score. The results of ISZ indicate that the gelatinolyzed areas were mainly localized in the

Establishment and evaluation of a transgenic mouse model of arthritis induced by overexpressing human tumor necrosis factor alpha

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Ge Li

2016-04-01

Full Text Available Tumor necrosis factor alpha (TNFα plays a key role in the pathogenesis of rheumatoid arthritis (RA. Blockade of TNFα by monoclonal antibody has been widely used for the therapy of RA since the 1990s; however, its mechanism of efficacy, and potential safety concerns of the treatment are still not fully understood. This study sought to establish a transgenic arthritic mouse model by overexpressing human TNFα (hTNFα and to apply this model as a means to evaluate therapeutic consequences of TNFα inhibitors. The transgenic mouse line (TgTC with FVB background was generated by incorporating 3′-modified hTNFα gene sequences. A progressively erosive polyarthritis developed in the TgTC mice, with many characteristics observed in human rheumatoid arthritis, including polyarticular swelling, impairment of movement, synovial hyperplasia, and cartilage and bone erosion. Gene expression analysis demonstrated that hTNFα is not only expressed in hyperplastic synovial membrane, but also in tissues without lesions, including brain, lung and kidney. Treatment of the TgTC mice with anti-hTNFα monoclonal antibodies (mAb significantly decreased the level of hTNFα in the diseased joint and effectively prevented development of arthritis in a dose-dependent response fashion. Our results indicated that the TgTC mice represent a genetic model which can be used to comprehensively investigate the pathogenesis and therapeutics of TNFα-related diseases.

Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis.

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Xu, Wei; Huang, Mingqing; Zhang, Yuqin; Li, Huang; Zheng, Haiyin; Yu, Lishuang; Chu, Kedan; Lin, Yu; Chen, Lidian

2016-05-01

Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor‑α and nuclear factor‑κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription‑polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE‑treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action.

Subclinical Synovitis Measured by Ultrasound in Rheumatoid Arthritis Patients With Clinical Remission Induced by Synthetic and Biological Modifying Disease Drugs.

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Cruces, Marcos; Al Snih, Soham; Serra-Bonett, Natalí; Rivas, Juan C

2017-10-09

Rheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage. To determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF. Hospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0=none to 3=severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N=37) and combination therapy with DMARD and anti-TNF (N=21) groups. A p-value <0.05 was considered statistically significant. Out of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found. Persistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Wnt/β-catenin Signaling in Osteoarthritis and in Other Forms of Arthritis.

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Zhou, Yachuan; Wang, Tingyu; Hamilton, John L; Chen, Di

2017-09-01

Arthritis defines a large group of diseases primarily affecting the joint. It is the leading cause of pain and disability in adults. Osteoarthritis (OA) affecting the knee or hip is the most common form among over 100 types of arthritis. Other types of arthritis include erosive hand OA, temporomandibular joint (TMJ) OA, facet joint OA, diffuse idiopathic skeletal hyperostosis (DISH), and spondyloarthritis (SpA). However, the specific molecular signals involved in the development and progression of OA and related forms of arthritis remain largely unknown. The canonical wingless/integrated (Wnt)/β-catenin signaling pathway could play a unique role in the pathogenesis of arthritis. In this review article, we will focus on the molecular mechanisms of Wnt/β-catenin signaling in the pathogenesis of OA and other types of arthritis. Emerging evidence demonstrates that Wnts and Wnt-related molecules are involved in arthritis development and progression in human genetic studies and in vitro studies. Also, mouse models have been generated to determine the role of Wnt/β-catenin signaling in the pathogenesis of arthritis. Wnt/β-catenin signaling represents a unique signaling pathway regulating arthritis development and progression, and the molecules in this particular pathway may serve as targets for the therapeutic intervention of arthritis. Mediators and downstream effectors of Wnt/β-catenin signaling are increased in OA as well other forms of arthritis, including DISH and SpA. Through extensive investigations, including pre-clinical studies in transgenic mice and translational and human studies, the Wnt/β-catenin signaling pathway has been proven to play roles in bone and joint pathology by directly affecting bone, cartilage, and synovial tissue; further, these pathologies can be reduced through targeting this pathway. Continued investigation into the distinct molecular signaling of the Wnt/β-catenin pathway will provide additional insights toward the therapeutic

Detection of Arthritis by Joint Scanning

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Maxfield, W. S. [Dept, of Radiology, Louisiana State University School of Medicine, New Orleans, LA (United States); Weiss, T. E.; Tutton, R. H.; Hidalgo, J. U. [Ochsner Clinic and Ochsner Foundation Hospital, New Orleans, LA (United States)

1969-05-15

Detection and identification of early arthritis is frequently difficult with routine methods. Several tracers, {sup 131}I human serum albumin (25 {mu}Ci/10 lb), {sup 99m}Tc human serum albumin (1-3 mCi), {sup 131}I iodipamide (40 {mu}Ci/10 lb), and {sup 99m}Tc pertechnetate (10 mCi), have been employed for joint scanning to detect synovitis produced by arthritis in joints of the extremities. When administered intravenously, the 25% increase in localization of these tracers in the synovial membrane, if there is active synovitis, can be demonstrated by scintillation scanning. This ability to detect synovitis at an early stage enables the joint scan to show areas of active synovitis not demonstrated on roentgenograms. The scan may objectively confirm or disprove questionable physical findings. From this standpoint the technique has been useful in determining whether joint pain is functional or due to arthritis as a negative localization tends to rule out active synovitis as the cause of the pain. The scan demonstration of a positive localization of the tracer in several joints when only one area is symptomatic is evidence that joint pain is due to systemic disease. The short half-life tracera permit serial studies to follow the course of an arthritis process. Use of {sup 99m}Tc pertechnetate and an Anger camera have made joint scanning a practical technique for clinical use. A review of the accuracy of joint scanning in 130 cases as compared to roentgenograms is presented. (author)

Paradoxical arthritis occurring during anti-TNF in patients with inflammatory bowel disease: histological and immunological features of a complex synovitis.

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Alivernini, Stefano; Pugliese, Daniela; Tolusso, Barbara; Bui, Laura; Petricca, Luca; Guidi, Luisa; Mirone, Luisa; Rapaccini, Gian Ludovico; Federico, Francesco; Ferraccioli, Gianfranco; Armuzzi, Alessandro; Gremese, Elisa

2018-01-01

Paradoxical arthritis under tumour necrosis factor inhibitor (TNF-i) for inflammatory bowel disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial tissue (ST) and colonic mucosa (CM) tissue in patients with IBD developing paradoxical arthritis under TNF-i. Patients with IBD without history of coexisting joint involvement who developed arthritis under TNF-i were enrolled. Each patient underwent ST biopsy and ileocolonoscopy with CM biopsies. ST and CM paired samples were stained through immunohistochemistry (IHC) for CD68, CD21, CD20, CD3 and CD117. Clinical and immunological parameters (anticitrullinated peptides antibodies (ACPA)-immunoglobulin (Ig)M/IgA rheumatoid factor (RF)) were collected. Psoriatic arthritis (PsA) and ACPA/IgM-RF/IgA-RF negative rheumatoid arthritis (RA) were enrolled as comparison. 10 patients with IBD (age 46.0±9.7 years, 13.2±9.9 years of disease duration, 2.5±1.6 years of TNF-i exposure, six with Crohn's disease and four with ulcerative colitis, respectively) were studied. At ST level, IHC revealed that patients with IBD with paradoxical arthritis showed more similar histological findings in terms of synovial CD68 + , CD21 + , CD20 + , CD3 + and CD117 + cells compared with PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing the CM specimens, patients with IBD showed the presence of CD68 + , CD3 + , CD117 + and CD20 + cells in 100%, 70%, 60% and 50% of cases, respectively, despite endoscopic remission. Finally, addition of conventional disease-modifying antirheumatic drugs and switch to ustekinumab were more effective than swapping into different TNF-i in patients with IBD with paradoxical arthritis. Patients with IBD may develop histologically proven synovitis during TNF-i, comparable to PsA. The inhibition of inflammatory pathways alternative to TNF (IL12/1L23) may be an effective therapeutic option for severe paradoxical articular manifestations.

Synovial Chondrosarcoma in the Hand and Wrist: A Case Report

International Nuclear Information System (INIS)

An, Yeong Yi; Kim, Jee Young; Kang, Seok Jin; Kang, Yong Koo; Baik, Jun Hyun

2010-01-01

Synovial chondrosarcoma is extremely rare and arises de novo or from malignant transformation of synovial chondromatosis. It commonly involves large joints, such as the knee or hip. Here, we present an unusual case of synovial chondrosarcoma from synovial chondromatosis in the hand and wrist, clearly demonstrating the characteristic findings on plain radiograph and MR imaging

Synovial Chondrosarcoma in the Hand and Wrist: A Case Report

Energy Technology Data Exchange (ETDEWEB)

An, Yeong Yi; Kim, Jee Young; Kang, Seok Jin; Kang, Yong Koo; Baik, Jun Hyun [Catholic University St. Vincent' s Hospital, Suwon (Korea, Republic of)

2010-01-15

Synovial chondrosarcoma is extremely rare and arises de novo or from malignant transformation of synovial chondromatosis. It commonly involves large joints, such as the knee or hip. Here, we present an unusual case of synovial chondrosarcoma from synovial chondromatosis in the hand and wrist, clearly demonstrating the characteristic findings on plain radiograph and MR imaging.

Role of the cholinergic nervous system in rheumatoid arthritis: aggravation of arthritis in nicotinic acetylcholine receptor alpha7 subunit gene knockout mice

NARCIS (Netherlands)

van Maanen, Marjolein A.; Stoof, Susanne P.; Larosa, Gregory J.; Vervoordeldonk, Margriet J.; Tak, Paul P.

2010-01-01

BACKGROUND: The alpha7 subunit of nicotinic acetylcholine receptors (alpha7nAChR) can negatively regulate the synthesis and release of proinflammatory cytokines by macrophages and fibroblast-like synoviocytes in vitro. In addition, stimulation of the alpha7nAChR can reduce the severity of arthritis

Influence of exogenous leptin on redox homeostasis in neutrophils and lymphocytes cultured in synovial fluid isolated from patients with rheumatoid arthritis

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Michał Gajewski

2016-07-01

Full Text Available Objectives : Leptin is an adipose cells derived hormone that regulates energy homeostasis within the body. Energy metabolism of immune cells influences their activity within numerous pathological states, but the effect of leptin on these cells in unclear. On the one hand, it was observed that leptin induces neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils exposed to leptin did not display detectable Ca 2+ ions mobilization or β 2 -integrin upregulation. In this study, we investigated the effect of leptin on the redox homeostasis in lymphocytes and neutrophils. Material and methods : Neutrophils and lymphocytes were isolated by density-gradient centrifugation of blood from healthy volunteers. Cells were cultured with or without leptin (100 ng/ml for lymphocytes and 500 ng/ml for neutrophils or with or without synovial fluid (85% for 0–72 h. Culture media were not changed during incubation. Cells were homogenized and homogenate was frozen until laboratory measurements. Redox homeostasis was assessed by the reduced glutathione (GSH vs. oxidized glutathione (GSSG ratio and membrane lipid peroxidation evaluation. Results : Lymphocytes cultured with leptin and synovial fluid showed a significant increase of the GSSG level. The GSSG/GSH ratio increased by 184 ±37%. In neutrophils incubated in a similar environment, the GSSG/GSH ratio increased by just 21 ±7%, and the effect was observed irrespectively of whether they were exposed to leptin or synovial fluid or both together. Neither leptin nor synovial fluid influenced lipid peroxidation in neutrophils, but in lymphocytes leptin intensified lipid peroxidation. Conclusions : Leptin altered the lymphocytes, but not neutrophils redox state. Because firstly neutrophils are anaerobic cells and have just a few mitochondria and secondly lymphocytes have typical aerobic metabolism, the divergence of our data supports the hypothesis that leptin induces oxidative stress by

Nonclassical Ly6C− Monocytes Drive the Development of Inflammatory Arthritis in Mice

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Alexander V. Misharin

2014-10-01

Full Text Available Different subsets and/or polarized phenotypes of monocytes and macrophages may play distinct roles during the development and resolution of inflammation. Here, we demonstrate in a murine model of rheumatoid arthritis that nonclassical Ly6C− monocytes are required for the initiation and progression of sterile joint inflammation. Moreover, nonclassical Ly6C− monocytes differentiate into inflammatory macrophages (M1, which drive disease pathogenesis and display plasticity during the resolution phase. During the development of arthritis, these cells polarize toward an alternatively activated phenotype (M2, promoting the resolution of joint inflammation. The influx of Ly6C− monocytes and their subsequent classical and then alternative activation occurs without changes in synovial tissue-resident macrophages, which express markers of M2 polarization throughout the course of the arthritis and attenuate joint inflammation during the initiation phase. These data suggest that circulating Ly6C− monocytes recruited to the joint upon injury orchestrate the development and resolution of autoimmune joint inflammation.

Quantitative MR characterization of disease activity in the knee in children with juvenile idiopathic arthritis: a longitudinal pilot study

International Nuclear Information System (INIS)

Workie, Dagnachew W.; Graham, T.B.; Laor, Tal; Racadio, Judy M.; Rajagopal, Akila; O'Brien, Kendall J.; Bommer, Wendy A.; Shire, Norah J.; Dardzinski, Bernard J.

2007-01-01

The development of a quantifiable and noninvasive method of monitoring disease activity and response to therapy is vital for arthritis management. The purpose of this study was to investigate the utility of quantitative dynamic contrast-enhanced MRI (DCE-MRI) based on pharmacokinetic (PK) modeling to evaluate disease activity in the knee and correlate the results with the clinical assessment in children with juvenile idiopathic arthritis (JIA). A group of 17 children with JIA underwent longitudinal clinical and laboratory assessment and DCE-MRI of the knee at enrollment, 3 months, and 12 months. A PK model was employed using MRI signal enhancement data to give three parameters, K trans ' (min -1 ), k ep (min -1 ), and V p ' and to calculate synovial volume. The PK parameters, synovial volumes, and clinical and laboratory assessments in most children were significantly decreased (P < 0.05) at 12 months when compared to the enrollment values. There was excellent correlation between the PK and synovial volume and the clinical and laboratory assessments. Differences in MR and clinical parameter values in individual subjects illustrate persistent synovitis when in clinical remission. A decrease in PK parameter values obtained from DCE-MRI in children with JIA likely reflects diminution of disease activity. This technique may be used as an objective follow-up measure of therapeutic efficacy in patients with JIA. MR imaging can detect persistent synovitis in patients considered to be in clinical remission. (orig.)

[The temporomandibular joint in juvenile idiopathic arthritis: what radiologists need to look for on magnetic resonance imaging].

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De La Hoz Polo, M; Navallas, M

2014-01-01

The term "juvenile idiopathic arthritis" (JIA) encompasses a group of arthritis of unknown cause with onset before the age of 16 years that last for at least 6 weeks. The prevalence of temporomandibular joint involvement in published series ranges from 17% to 87%. Temporomandibular joint involvement is difficult to detect clinically, so imaging plays a key role in diagnosis and monitoring treatment. MRI is the technique of choice for the study of arthritis of the temporomandibular joint because it is the most sensitive technique for detecting acute synovitis and bone edema. Power Doppler ultrasonography can also detect active synovitis by showing the hypervascularization of the inflamed synovial membrane, but it cannot identify bone edema. This article describes the MRI technique for evaluating the temporomandibular joint in patients with juvenile idiopathic arthritis, defines the parameters to look for, and illustrates the main findings. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

Cartilage proteoglycans inhibit fibronectin-mediated adhesion

Science.gov (United States)

Rich, A. M.; Pearlstein, E.; Weissmann, G.; Hoffstein, S. T.

1981-09-01

Normal tissues and organs show, on histological examination, a pattern of cellular and acellular zones that is characteristic and unique for each organ or tissue. This pattern is maintained in health but is sometimes destroyed by disease. For example, in mobile joints, the articular surfaces consist of relatively acellular hyaline cartilage, and the joint space is enclosed by a capsule of loose connective tissue with a lining of fibroblasts and macrophages. In the normal joint these cells are confined to the synovial lining and the articular surface remains acellular. In in vitro culture, macrophages and their precursor monocytes are very adhesive, and fibroblasts can migrate and overgrow surfaces such as collagen or plastic used for tissue culture. The fibroblasts adhere to collagen by means of fibronectin, which they synthesize and secrete1. Because the collagen of cartilage is capable of binding serum fibronectin2 and fibronectin is present in cartilage during its development3, these cells should, in theory, slowly migrate from the synovial lining to the articular surface. It is their absence from the articular cartilage in normal circumstances, and then presence in such pathological states as rheumatoid arthritis, that is striking. We therefore set out to determine whether a component of cartilage could prevent fibroblast adherence in a defined adhesion assay. As normal cartilage is composed of 50% proteoglycans and 50% collagen by dry weight4, we tested the possibility that the proteoglycans in cartilage inhibit fibroblast adhesion to collagen. We present here evidence that fibroblast spreading and adhesion to collagenous substrates is inhibited by cartilage proteoglycans.

Septic arthritis of the hip in a Cambodian child caused by multidrug-resistant Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin treated with ceftriaxone and azithromycin.

Science.gov (United States)

Pocock, J M; Khun, P A; Moore, C E; Vuthy, S; Stoesser, N; Parry, C M

2014-08-01

Septic arthritis is a rare complication of typhoid fever. A 12-year-old boy without pre-existing disease attended a paediatric hospital in Cambodia with fever and left hip pain. A hip synovial fluid aspirate grew multidrug-resistant Salmonella enterica ser. Typhi with intermediate susceptibility to ciprofloxacin. Arthrotomy, 2 weeks of intravenous ceftriaxone and 4 weeks of oral azithromycin led to resolution of symptoms. The optimum management of septic arthritis in drug-resistant typhoid is undefined.

Synovial cysts: clinical and neuroradiological aspects

International Nuclear Information System (INIS)

Artico, M.; Cervoni, L.; Carloia, S.; Stevanato, G.; Mastantuono, M.; Nucci, F.

1997-01-01

Lumbar and intraneural synovial cysts are uncommon lesions. although their incidence has increased since the introduction of MRI. The authors describe the results of a study comprising 23 patients with synovial cyst (5 lumbar, 19 intraneural). Neuroradiological investigations included CT scan and MRI; however, it was not always possible to diagnose the nature of the lesion. In 18 cases the lesion was removed totally including its capsule; in the other 5 cases it was removed subtotally. Seven of the 23 patients presented a total remission of symptoms/signs, 11 improved and 5 remained unchanged. The importance of treating synovial cysts as radically as possible is discussed together with their most significant clinical and neuroradiological aspects. (author)

Cyr61 induces IL-6 production by fibroblast-like synoviocytes promoting Th17 differentiation in rheumatoid arthritis.

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Lin, Jinpiao; Zhou, Zhou; Huo, Rongfen; Xiao, Lianbo; Ouyang, Guilin; Wang, Li; Sun, Yue; Shen, Baihua; Li, Dangsheng; Li, Ningli

2012-06-01

Cysteine-rich protein 61 (Cyr61)/CCN1 is a product of an immediate early gene and functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) promotes FLS proliferation and participates in RA pathogenesis with the IL-17-dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown. In the current study, we explored the potential role of Cyr61 as a proinflammatory factor in RA pathogenesis. We found that Cyr61 treatment dramatically induced IL-6 production in FLS isolated from RA patients. Moreover, IL-6 production was attenuated by Cyr61 knockdown in FLS. Mechanistically, we showed that Cyr61 activated IL-6 production via the αvβ5/Akt/NF-κB signaling pathway. Further, using a coculture system consisting of purified CD4(+) T cells and RA FLS, we found that RA FLS stimulated Th17 differentiation, and the pro-Th17 differentiation effect of RA FLS can be attenuated or stimulated by Cyr61 RNA interference or addition of exogenous Cyr61, respectively. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the anti-Cyr61 mAb led to reduction of IL-6 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo. Taken together, our results reveal a novel role of Cyr61 in promoting Th17 development in RA via upregulation of IL-6 production by FLS, thus adding a new layer into the functional interplay between FLS and Th17 in RA pathogenesis. Our study also suggests that targeting of Cyr61 may represent a novel strategy in RA treatment.

Hyaluronate synthesis by synovial villi in organ culture

International Nuclear Information System (INIS)

Myers, S.L.; Christine, T.A.

1983-01-01

Individual canine synovial villi were used to establish short-term synovial organ cultures. These villi incorporated 3 H-glucosamine into highly-polymerized 3 H-hyaluronic acid ( 3 H-HA), which was the only 3 H-glycosaminoglycan identified in the culture medium. Some 3 H-HA, and larger amounts of other 3 H-glycosaminoglycans, were recovered from cultured tissues. Culture medium 3 H-HA content was proportional to the surface area of cultured villi. Organ cultures of nonvillous synovium were compared with villi; nonvillous cultures synthesized less 3 H-HA per mm2 of their synovial intimal surface than villi. These cultures complement cell culture techniques for in vitro studies of synovial lining cell function

Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

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A. Hanyecz

2014-01-01

Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA, and CD4+ T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.

Synovial chondromatosis of the shoulder: imaging findings

International Nuclear Information System (INIS)

Terazaki, Carlos Renato Ticianelli; Trippia, Carlos Henrique; Caboclo, Maria Fernanda Sales Ferreira; Medaglia, Carla Regina Miranda

2014-01-01

Synovial chondromatosis is a benign condition characterized by synovial proliferation and metaplasia, with development of cartilaginous or osteocartilaginous nodules within a joint, bursa or tendon sheath. In the shoulder, synovial osteochondromatosis may occur within the glenohumeral joint and its recesses (including the tendon sheath of the biceps long head), and in the subacromial-deltoid bursa. Such condition can be identified either by radiography, ultrasonography or magnetic resonance imaging, showing typical features according to each method. Radiography commonly shows ring-shaped calcified cartilages and periarticular soft tissues swelling with erosion of joint margins. Ultrasonography demonstrates hypoechogenic cartilaginous nodules with progressive increase in echogenicity as they become calcified, with development of posterior acoustic shadow in case of ossification. Besides identifying cartilaginous nodules, magnetic resonance imaging can also demonstrate the degree of synovial proliferation. The present study is aimed at describing the imaging findings of this entity in the shoulder. (author)

Synovial chondromatosis of the shoulder: imaging findings

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Carlos Renato Ticianelli Terazaki

2014-02-01

Full Text Available Synovial chondromatosis is a benign condition characterized by synovial proliferation and metaplasia, with development of cartilaginous or osteocartilaginous nodules within a joint, bursa or tendon sheath. In the shoulder, synovial osteochondromatosis may occur within the glenohumeral joint and its recesses (including the tendon sheath of the biceps long head, and in the subacromial-deltoid bursa. Such condition can be identified either by radiography, ultrasonography or magnetic resonance imaging, showing typical features according to each method. Radiography commonly shows ring-shaped calcified cartilages and periarticular soft tissues swelling with erosion of joint margins. Ultrasonography demonstrates hypoechogenic cartilaginous nodules with progressive increase in echogenicity as they become calcified, with development of posterior acoustic shadow in case of ossification. Besides identifying cartilaginous nodules, magnetic resonance imaging can also demonstrate the degree of synovial proliferation. The present study is aimed at describing the imaging findings of this entity in the shoulder.

Ultrasonography and color Doppler in juvenile idiopathic arthritis: diagnosis and follow-up of ultrasound-guided steroid injection in the ankle region. A descriptive interventional study

DEFF Research Database (Denmark)

Laurell, Louise; Court-Payen, Michel; Nielsen, Susan

2011-01-01

The ankle region is frequently involved in juvenile idiopathic arthritis (JIA) but difficult to examine clinically due to its anatomical complexity. The aim of the study was to evaluate the role of ultrasonography (US) of the ankle and midfoot (ankle region) in JIA. Doppler-US detected synovial h...

Synovial Fluid Analysis

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... Plasma Free Metanephrines Platelet Count Platelet Function Tests Pleural Fluid Analysis PML-RARA Porphyrin Tests Potassium Prealbumin ... is being tested? Synovial fluid is a thick liquid that acts as a lubricant for the body's ...

A new inhibitor of synovial phospholipase A2 from fermentations of Penicillium sp. 62-92.

Science.gov (United States)

Witter, L; Anke, T; Sterner, O

1998-01-01

Penidiamide, a new tripetide containing dehydrotryptamine, glycine and anthranilic acid linked together by two amide bonds, and oxindole were isolated from submerged cultures of Penicillium sp. 62-92. Both compounds preferentially inhibited human synovial phospholipase A2, penidiamide with an IC50 of 30 microM and oxindole of 380 microM. With the exception of U 937 cells (leukemia, human), no cytotoxic activities were detected against HL-60- (leukemia, human), HeLa S3- (epitheloid carcinoma, human), BHK 21- (kidney fibroblasts, hamster), and L1210-cells (leukemia, mouse). No antimicrobial activity was detected for oxindole, and only weak antibacterial activity for penidiamide. The structure of penidiamide was elucidated by spectroscopic methods.

Multimodality management of primary diaphragmatic synovial sarcoma: First report

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Preyas J Vaidya

2016-01-01

Full Text Available Synovial cell sarcoma is an extremely rare tumor of mesenchymal origin. It commonly affects the soft tissues of the extremities but could possibly origin from the head and neck, heart, lung, pleura, mediastinum, esophagus, abdominal wall and the mesentery, and retroperitoneum. Primary synovial sarcoma of pleura, mediastinum, and lung have been reported. Primary synovial sarcoma of the diaphragm has not been reported to the best of our knowledge. We report a case of primary synovial cell sarcoma of the diaphragm presenting as a recurrent pleural effusion and pain in the left hypochondrium managed with multimodality approach.

siRNA targeting PLK-1 induces apoptosis of synoviocytes in rheumatoid arthritis

International Nuclear Information System (INIS)

Wada, Makoto; Kawahito, Yutaka; Kimura, Shinya; Kohno, Masataka; Ishino, Hidetaka; Kimura, Mizuho; Omoto, Atsushi; Yamamoto, Aihiro; Hamaguchi, Masahide; Tsubouchi, Yasunori; Tokunaga, Daisaku; Hojo, Tatsuya; Ashihara, Eishi; Maekawa, Taira; Yoshikawa, Toshikazu

2007-01-01

Polo-like kinase-1 (PLK-1) is a member of the PLK family and participates in the control of cell mitosis. Here, we show that immunoreactive PLK-1 is strongly expressed in synoviocytes and some infiltrative mononuclear cells in synovial tissues from patients with rheumatoid arthritis (RA), while patients with osteoarthritis and injury show little or no expression of PLK-1 in synovial tissues. Western blot analysis shows that PLK is expressed and its expression is enhanced by IL-1β in RA synoviocytes. IL-1β also enhanced the cell growth of RA synoviocytes. Moreover, siRNA targeted against PLK-1 significantly decreases the expression of PLK-1 of RA synoviocytes stimulated by IL-1β and suppresses the proliferation of these synoviocytes through apoptosis. These findings suggest that PLK-1 plays a critical role in the proliferation of RA synoviocytes leading to bone destruction, and siRNA against PLK-1 is potentially useful for the treatment of RA

Magnetic particle translation as a surrogate measure for synovial fluid mechanics.

Science.gov (United States)

Shah, Yash Y; Maldonado-Camargo, Lorena; Patel, Neal S; Biedrzycki, Adam H; Yarmola, Elena G; Dobson, Jon; Rinaldi, Carlos; Allen, Kyle D

2017-07-26

The mechanics of synovial fluid vary with disease progression, but are difficult to quantify quickly in a clinical setting due to small sample volumes. In this study, a novel technique to measure synovial fluid mechanics using magnetic nanoparticles is introduced. Briefly, microspheres embedded with superparamagnetic iron oxide nanoparticles, termed magnetic particles, are distributed through a 100μL synovial fluid sample. Then, a permanent magnet inside a protective sheath is inserted into the synovial fluid sample. Magnetic particles translate toward the permanent magnet and the percentage of magnetic particles collected by the magnet in a given time can be related to synovial fluid viscosity. To validate this relationship, magnetic particle translation was demonstrated in three phases. First, magnetic particle translation was assessed in glycerol solutions with known viscosities, demonstrating that as fluid viscosity increased, magnetic particle translation decreased. Next, the relationship between magnetic particle translation and synovial fluid viscosity was assessed using bovine synovial fluid that was progressively degenerated via ultrasonication. Here, particle collection in a given amount of time increased as fluid degenerated, demonstrating that the relationship between particle collection and fluid mechanics holds in non-Newtonian synovial fluid. Finally, magnetic particle translation was used to assess differences between healthy and OA affected joints in equine synovial fluid. Here, particle collection in a given time was higher in OA joints relative to healthy horses (pfluid mechanics in limited volumes of synovial fluid sample. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

Science.gov (United States)

Muschter, Dominique; Schäfer, Nicole; Stangl, Hubert; Straub, Rainer H.; Grässel, Susanne

2015-01-01

Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors. PMID:26431344

Synovial sarcoma

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Sucari S.C. Vlok

2014-12-01

Full Text Available Synovial sarcoma is a malignant, predominantly juxta-articular, soft-tissue tumour representing approximately 10% of all soft-tissue sarcomas. Frequently initially incorrectly diagnosed as a benign lesion, it should be considered as a diagnosis when a young adult patient presents with a calcified juxta-articular soft-tissue mass of insidious onset.

Interleukin-21 receptor deficiency increases the initial toll-like receptor 2 response but protects against joint pathology by reducing Th1 and Th17 cells during streptococcal cell wall arthritis.

Science.gov (United States)

Marijnissen, Renoud J; Roeleveld, Debbie M; Young, Deborah; Nickerson-Nutter, Cheryl; Abdollahi-Roodsaz, Shahla; Garcia de Aquino, Sabrina; van de Loo, Fons A J; van Spriel, Annemiek B; Boots, Annemieke M H; van den Berg, Wim B; Koenders, Marije I

2014-04-01

The cytokine interleukin-21 (IL-21) can have both proinflammatory and immunosuppressive effects. The purpose of this study was to investigate the potential dual role of IL-21 in experimental arthritis in relation to Th17 cells. Antigen-induced arthritis (AIA) and chronic streptococcal cell wall (SCW) arthritis were induced in IL-21 receptor-deficient (IL-21R(-/-) ) and wild-type mice. Knee joints, synovial tissue, and serum were analyzed for arthritis pathology and inflammatory markers. During AIA and chronic SCW arthritis, IL-21R deficiency protected against severe inflammation and joint destruction. This was accompanied by suppressed serum IgG1 levels and antigen-specific T cell responses. Levels of IL-17 were reduced during AIA, and synovial lymphocytes isolated during SCW arthritis for flow cytometry demonstrated that mainly IL-17+ interferon-γ (IFNγ)-positive T cells were reduced in IL-21R(-/-) mice. However, during the acute phases of SCW arthritis, significantly higher joint swelling scores were observed, consistent with enhanced tumor necrosis factor and IL-6 expression. Interestingly, IL-21R(-/-) mice were significantly less capable of up-regulating suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 messenger RNA. IL-21 stimulation also affected the Toll-like receptor 2 (TLR-2)/caspase recruitment domain 15 response to SCW fragments in vitro, indicating that impaired SOCS regulation in the absence of IL-21 signaling might contribute to the increased local activation during SCW arthritis. In contrast to the proinflammatory role of IL-21 in adaptive immunity, which drives IL-17+IFN+ cells and joint pathology during chronic experimental arthritis, IL-21 also has an important immunosuppressive role, presumably by inhibiting TLR signaling via SOCS-1 and SOCS-3. If this dual role of IL-21 in various immune processes is present in human disease, it could make IL-21 a difficult therapeutic target in rheumatoid arthritis. Copyright © 2014 by the American

Citrullination: the loss of tolerance and development of autoimmunity in rheumatoid arthritis

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G. Ferraccioli

2011-09-01

Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease characterized by synovial inflammation and pannus formation, which can lead to severe destruction of cartilage and bone. Several self proteins have been suggested to be disease-driving autoantigens. Moreover the presence of autoantibodies to citrullinated proteins in sera of patients with RA enhances the strength of this hypothesis. Proteins are encoded by a limited number of genes in our genome. Post-translational modifications such as phosphorylation, glycosylation and citrullination can increase the morphological and the functional diversity of the proteome.

Reactive arthritis in relation to internal derangements of the temporomandibular joint: a case control study.

Science.gov (United States)

Lund, Bodil; Holmlund, Anders; Wretlind, Bengt; Jalal, Shah; Rosén, Annika

2015-09-01

The aim of this study was to find out if reactive arthritis was involved in the aetiology of chronic closed lock of the temporomandibular joint (TMJ) by looking for bacterial antigens in the synovial membrane of the TMJ, and by studying the antibody serology and carriage of human leucocyte antigen (HLA) B27 in patients with chronic closed lock. Patients with reciprocal clicking and healthy subjects acted as controls. We studied a total of 43 consecutive patients, 15 with chronic closed lock, 13 with reciprocal clicking, and 15 healthy controls with no internal derangements of the TMJ. Venous blood samples were collected from all subjects for measurement of concentrations of HLA tissue antigen and serology against Chlamydia trachomatis, Yersinia enterocolitica, Salmonella spp., Campylobacter jejuni, and Mycoplasma pneumoniae. Samples of synovial tissue from patients with closed lock and reciprocal clicking were obtained during discectomy and divided into two pieces, the first of which was tested by strand displacement amplification for the presence of C trachomatis, and the second of which was analysed for the presence of species-specific bacterial DNA using 16s rRNA pan-polymerase chain reaction (PCR). There were no significant differences between the groups in the incidence of antibodies against M pneumoniae, Salmonella spp. or Y enterocolitica. No patient had antibodies towards C trachomatis or C jejuni. We found no bacterial DNA in the synovial fluid from any patient. The HLA B27 antigen was present in 2/15 subjects in both the closed lock and control groups, and none in the reciprocal clicking group. In conclusion, reactive arthritis does not seem to be the mechanism of internal derangement of the TMJ. Copyright © 2015. Published by Elsevier Ltd.

Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response.

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Tue Wenzel Kragstrup

Full Text Available In rheumatoid arthritis (RA immune activation and presence of autoantibodies may precede clinical onset of disease, and joint destruction can progress despite remission. However, the underlying temporal changes of such immune system abnormalities in the inflammatory response during treat-to-target strategies remain poorly understood. We have previously reported low levels of the soluble form of CD18 (sCD18 in plasma from patients with chronic RA and spondyloarthritis. Here, we study the changes of sCD18 before and during treatment of early RA and following arthritis induction in murine models of rheumatoid arthritis.The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1 plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort, 2 plasma from chronic RA patients, 3 serum from SKG and CIA mice following arthritis induction, and 4 supernatants from synovial fluid mononuclear cells (SFMCs and peripheral blood mononuclear cells (PBMCs from 6 RA patients cultured with TNFα or adalimumab.Plasma levels of sCD18 were decreased in chronic RA patients compared with early RA patients and in early RA patients compared with healthy controls. After 12 months of treatment the levels in early RA patients were similar to healthy controls. This normalization of plasma sCD18 levels was more pronounced in patients with very early disease who achieved an early ACR response. Plasma sCD18 levels were associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above baseline followed by a decline. Shedding of CD18 from RA SFMC and RA PBMC cultures was increased by TNFα and decreased by adalimumab.The plasma sCD18 levels were altered in patients with RA, in mice

Protein, RNA, and DNA synthesis in cultures of skin fibroblasts from healthy subjects and patients with rheumatic diseases

International Nuclear Information System (INIS)

Abakumova, O.Y.; Kutsenko, N.G.; Panasyuk, A.F.

1985-01-01

To study the mechanism of the lasting disturbance of fibroblast function, protein, RNA and DNA synthesis was investigated in skin fibroblasts from patients with rheumatoid arthritis (RA) and systemic scleroderma (SS). The labeled precursors used to analyze synthesis of protein, RNA, and DNA were 14 C-protein hydrolysate, ( 14 C)uridine, and ( 14 C) thymidine. Stimulation was determined by measuring incorporation of ( 14 C)proline into fibroblast proteins. During analysis of stability of fast-labeled RNA tests were carried out to discover whether all measurable radioactivity belonged to RNA molecules

Synovial membrane involvement in osteoarthritic temporomandibular joints - A light microscopic study

NARCIS (Netherlands)

Dijkgraaf, LC; Liem, RSB; deBont, LGM

Objective. To study the light microscopic characteristics of the synovial membrane of osteoarthritic temporomandibular joints to evaluate synovial membrane involvement in the osteoarthritic process. Study design. Synovial membrane biopsies were obtained during unilateral arthroscopy in 40 patients.

Magnetic resonance imaging of the wrist in early rheumatoid arthritis: a pictorial essay

International Nuclear Information System (INIS)

Stewart, N.R.; Crabbe, J.P.; McQueen, F.M.

2001-01-01

This pictorial essay describes the changes seen in the wrist in early rheumatoid arthritis (RA) on MRI. Magnetic resonance imaging can demonstrate bone erosions, bone marrow signal changes, synovitis and tenosynovitis in early rheumatoid arthritis. Magnetic resonance imaging of the wrist can identify erosions in RA earlier than plain radiographs and can detect more erosions. Common sites include the capitate, lunate and scaphoid. Bone marrow signal changes occur frequently and are most common in the capitate, lunate and triquetrum. Synovial thickening and enhancement are clearly demonstrated with MRI and are most commonly seen in the radiocarpal joint (RCJ). Tenosynovitis can be seen in the wrist in more than half of patients presenting with RA. This most commonly involves the extensor carpi ulnaris tendon and is seen as sheath fluid, thickening and enhancement. Copyright (2001) Blackwell Science Pty Ltd

Imaging appearances of synovial plicae syndrome of the knee

OpenAIRE

Osama Abdalla Mabrouk Kheiralla

2016-01-01

Synovial plicae are synovial folds that may be found as intraarticular structures within the knee joint. They are remnants of incomplete resorption of mesenchymal tissue during fetal development. Synovial plicae, if present, are supposed to be non-pathological and asymptomatic, however if they are exposed to special events like direct trauma or repeated activities, they may be inflamed and become fibrosed and rigid and irritates the synovium of the underlying femoral condyle resul...

A double patella-like condition secondary to synovial osteochondromatosis

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Kajikawa Yoshiteru

2012-09-01

Full Text Available Abstract To our knowledge, this is the first case of synovial osteochondromatosis in a patient presenting with a double patella-like condition. The true duplication of the patella, which is called double patella, is extremely rare. In our case, the operative and histopathological findings showed that the double patella-like condition was secondarily induced by synovial osteochondromatosis. Synovial osteochondromatosis should be considered as a differential diagnosis for congenital double patella.

Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus.

Science.gov (United States)

Cole, Suzanne; Walsh, Alice; Yin, Xuefeng; Wechalekar, Mihir D; Smith, Malcolm D; Proudman, Susanna M; Veale, Douglas J; Fearon, Ursula; Pitzalis, Costantino; Humby, Frances; Bombardieri, Michele; Axel, Amy; Adams, Homer; Chiu, Christopher; Sharp, Michael; Alvarez, John; Anderson, Ian; Madakamutil, Loui; Nagpal, Sunil; Guo, Yanxia

2018-05-02

Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target. We demonstrated that the plasma cell/plasmablast-related genes CD38, XBP1, IRF4, PRDM1, IGJ and TNFSF13B are significantly up-regulated in synovial biopsies from patients with arthralgia, undifferentiated arthritis (UA), early RA and established RA as compared to healthy controls and control patients with osteoarthritis. In addition, the highest CD38 expression was observed on plasma cells and plasmablasts compared to natural killer (NK) cells, classical dendritic cells (DCs), plasmacytoid DCs (pDCs) and T cells, in blood from healthy controls and patients with SLE and RA. Furthermore, IHC showed CD38 staining in the same region as CD3 and CD138 staining in synovial tissue biopsies from patients with early RA. Most importantly, our data show for the first time that daratumumab effectively depletes plasma cells/plasmablasts in PBMC from patients with SLE and RA in a dose-dependent manner ex vivo. These results indicate that CD38 may be a potential target for RA disease interception and daratumumab should be evaluated clinically for the treatment of both RA and SLE.

Potential of Topical Curcumin in Reduction of TNF-α expression and Synovium Hyperplasia on Wistar Rats of Rheumatoid Arthritis Model

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Ferri Widodo

2016-10-01

Full Text Available Rheumatoid arthritis is a chronic inflammatory autoimmune disease associated with articular and systemic effects. This disease affects synovial joints covered by a special tissue called synovium. Curcumin has a potent antioxidant, antiinflammatory agent, antiangiogenic and anticarcinogenic. Curcumin can downregulate the expression of various proinflammatory cytokines and is reported beneficial effects in arthritis, but has a poor solubility dan bioavailability as well. The purpose of this research was to study the potential of liposomes topikal curcumin in reducing athritis score, reducing the expression of TNF-α and histopathological synovium hyperplasia of hind paw on Wistar rats with CFA that had been treated with topical curcumin. In this study, rats were divided into 7 groups: positive control, negative control, rheumatoid arthritis with topical curcumin therapy of 90 mg/kg BW, rheumatoid arthritis with topical curcumin therapy of 110 mg/kg BW, rheumatoid arthritis with topical curcumin therapy of 200 mg/kg BW, rheumatoid arthritis with methotrexate therapy, rheumatoid arthritis with placebo therapy. Results from this experiment indicated that topical curcumin has no significant to the arthritis score, significantly effect to percentase expression of TNF-α (p<0.05 and could decrease synovium hyperplasia based on histophatology examination. It could be concluded that therapy of topical curcumin could decrease the expression of TNF- α and synovium hyperplasia in rheumatoid arthritis rat.

Monocyte scintigraphy in rheumatoid arthritis: the dynamics of monocyte migration in immune-mediated inflammatory disease.

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Rogier M Thurlings

2009-11-01

Full Text Available Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA, a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man.We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT. We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99mTc-HMPAO. Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4 x 10(-3 (0.95-5.1 x 10(-3 % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion.The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention.

Investigations in the scintiscanning of joints of animals with experimental and rheumatoid arthritis

International Nuclear Information System (INIS)

Hanheide, M.

1982-01-01

In 69 guinea pigs with experimental hyperergic arthritis scintiscanning was done to study the course of the inflammation and the deposition of the radionuclides used. During the first days there was an added storage in the inflamed joints of those animals on whom scintiscanning with Tc99m04 had been performed. The accumulation of Tc99m04 in the joints was due to its uptake by synovial tissue and hydrarthrosis as shown by scintiscanning after haemorrhage and perfusion, macroscopic autoradiography and measurements of radioactivity in tissue samples. In 13 animals with rheumatoid arthritis scintiscanning was done twice with Tc99m04 and three times with Tc99mMDP over a period of 13 to 21 months; concomitantly laboratory tests and X-rays were conducted. After Tc99m04 there was a fall in the scintigraphic inflammation index during treatment. That index was determined by forming the quotient from the activities established above the proximal interphalangeal joints and the tibial head. Scintiscanning with Tc99mMDP led to a fall of the inflammation index in animals with classical rheumatoid arthritis, whereas in the ones with probable rheumatoid arthritis it again rose after an initial fall. Unlike x-ray investigation, scintiscanning permits an early diagnosis and course control. (orig.) [de

Synovial Sarcoma of the Buccal Mucosa: A Rare Case Report

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Kumar T. S. Mahesh

2013-01-01

Full Text Available Synovial sarcoma (SS is a rare malignant neoplasm that arises most commonly in joint capsules and articular tendons, but its relationship to the synovium is not always obvious. Synovial sarcoma is a malignant soft tissue tumor representing 5.6% to 10% of all soft tissue sarcomas. They are termed SS because of their histologic resemblance to the synovium, but they rarely involve a synovial structure and are thought to arise from pluripotential mesenchymal cells. The tumor usually occurs in close association with tendon sheaths, bursae, and joint capsules, primarily in the para-articular regions of the extremities, with approximately 9% occurring in the head and neck region. Synovial sarcoma has been reported rarely in the oral cavity. We report a very rare case of Synovial sarcoma of the buccal mucosa in a 24-year-old male patient.

Soft tissue changes in the metacarpal region of the hand in rheumatoid arthritis

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Fischer, E.

1984-11-01

Rheumatoid arthritis causes changes in the soft tissues in the metacarpal portion of the hand which can be demonstrated by low Kv exposures. Indirect signs of inflammation consist of oedema extending from the synovial compartments to the skin, the subcutaneous tissues, the intermuscular fat septa and the peritendinous tissue. Increased blood flow leads to dilatation of veins. Direct signs of inflammation consists of tenosynovitis and synovitis of the joints, with enlargement of the corresponding compartments. Limited mobility of the hand over a long period, or improvement in motility are paralleled by changes in muscle mass.

Aspergillus arthritis: analysis of clinical manifestations, diagnosis, and treatment of 31 reported cases.

Science.gov (United States)

Gamaletsou, Maria N; Rammaert, Blandine; Bueno, Marimelle A; Sipsas, Nikolaos V; Moriyama, Brad; Kontoyiannis, Dimitrios P; Roilides, Emmanuel; Zeller, Valerie; Taj-Aldeen, Saad J; Henry, Michael; Petraitis, Vidmantas; Denning, David W; Lortholary, Olivier; Walsh, Thomas J

2017-04-01

Aspergillus arthritis is a debilitating form of invasive aspergillosis. Little is known about its epidemiology, clinical manifestations, laboratory features, treatment, and prognosis. Cases of Aspergillus arthritis were reviewed in the English literature from 1967 through 2015 for variables of arthritis with Aspergillus spp. recovered from joint and/or adjacent bone, underlying conditions, symptoms, signs, inflammatory biomarkers, diagnostic imaging, management, and outcome. Among 31 evaluable cases, 87% were males and 13% pediatric. Median age was 50 y (range 1-83 y). Seventeen (55%) patients were immunosuppressed with such conditions as hematological malignancies (26%), corticosteroids (39%), and/or transplantation (26%). Approximately one-half (52%) of patients had hematogenous seeding of the joint, and more than 80% had de novo infection with no prior antifungal therapy. Oligoarticular infection (2-3 joints) occurred in 45% and contiguous osteomyelitis was present in 61%. Clinical manifestations included pain (87%), edema (26%), and limited function (23%), with knees (35%), intervertebral discs (26%), and hips (16%) being most commonly infected. Aspergillus fumigatus constituted 77% of cases followed by Aspergillus flavus in 13%, Aspergillus niger in 3%, and not specified in 7%. Median ESR was 90 mm/hr and median CRP was 3.6 mg/dl. Median synovial fluid WBC was 17,200/μL (7,300-128,000) with 72% PMNs (range 61-92). Osteolysis occurred in 35%, and soft-tissue extension 47%. Nineteen patients (61%) were managed with combined medical and surgical therapy, 10 (32%) with medical therapy only, and 2 (6%) surgery only. Amphotericin B and itraconazole were the most frequently used agents with median duration of therapy of 219 days (range 30-545). Surgical interventions included debridement in 61%, drainage 19%, and amputation 6%. Complete or partial response was achieved in 71% and relapse occurred in 16%. Medical therapy was reinstituted with successful outcome in

Synovial sarcoma mechanisms

DEFF Research Database (Denmark)

Svejstrup, Jesper Q

2013-01-01

Human synovial sarcoma is caused by a chromosome translocation, which fuses DNA encoding SSX to that encoding the SS18 protein. Kadoch and Crabtree now show that the resulting cellular transformation stems from disruption of the normal architecture and function of the human SWI/SNF (BAF) complex....

Temporomandibular Joint Septic Arthritis

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Gianfranco Frojo, MD

2018-01-01

Full Text Available Summary:. Infection of the temporomandibular joint (TMJ is a rare pediatric condition resulting from the introduction of pathogens into the joint by hematogenous seeding, local extension, or trauma. Early recognition of the typical signs and symptoms including fever, trismus, preauricular swelling, and TMJ region tenderness are critical in order to initiate further evaluation and prevent feared complications of fibrosis, ankylosis, abnormal facial structure, or persistence of symptoms. Contrast-enhanced computed tomography with ancillary laboratory analysis including erythrocyte sedimentation rate, C-reactive protein, and white blood cell count are beneficial in confirming the suspected diagnosis and monitoring response to therapy. Initial intervention should include empiric parenteral antibiotics, early mandibular mobilization, and joint decompression to provide synovial fluid for analysis including cultures. This report describes a case of TMJ bacterial arthritis in a healthy 6-year-old male who was promptly treated nonsurgically with intravenous antibiotics and localized needle joint decompression with return to normal function after completion of oral antibiotics and physical therapy.

Changes in concentrations of haemostatic and inflammatory biomarkers in synovial fluid after intra-articular injection of lipopolysaccharide in horses

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Andreassen, Stine Mandrup; Vinther, Anne Mette Lindberg; Nielsen, Søren Saxmose

2017-01-01

BACKGROUND: Septic arthritis is a common and potentially devastating disease characterized by severe intra-articular (IA) inflammation and fibrin deposition. Research into equine joint pathologies has focused on inflammation, but recent research in humans suggests that both haemostatic and inflam......BACKGROUND: Septic arthritis is a common and potentially devastating disease characterized by severe intra-articular (IA) inflammation and fibrin deposition. Research into equine joint pathologies has focused on inflammation, but recent research in humans suggests that both haemostatic...... and inflammatory pathways are activated in the joint compartment in arthritic conditions. The aim of this study was to characterize the IA haemostatic and inflammatory responses in horses with experimental lipopolysaccharide (LPS)-induced joint inflammation. Inflammation was induced by IA injection of LPS into one...... antebrachiocarpal joint of six horses. Horses were evaluated clinically with subjective grading of lameness, and blood and synovial fluid (SF) samples were collected at post injection hours (PIH) -120, -96, -24, 0, 2, 4, 8, 16, 24, 36, 48, 72 and 144. Total protein (TP), white blood cell counts (WBC), serum amyloid...

Magnetic resonance imaging, radiography, and scintigraphy of the finger joints: one year follow up of patients with early arthritis. The TIRA Group

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Klarlund, Mette; Østergaard, Mikkel; Jensen, K E

2000-01-01

OBJECTIVES: To evaluate synovial membrane hypertrophy, tenosynovitis, and erosion development of the 2nd to 5th metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints by magnetic resonance imaging in a group of patients with rheumatoid arthritis (RA) or suspected RA followed up for one......, and tenosynovitis score. RESULTS: MRI detected progression of erosions earlier and more often than did radiography of the same joints; at baseline the MRI to radiography ratio was 28:4. Erosions were exclusively found in patients with RA at baseline or fulfilling the ACR criteria at one year. At one year follow up......, scores of MR synovial membrane hypertrophy, tenosynovitis, and scintigraphic tracer accumulation had not changed significantly from baseline; in contrast, swollen and tender joint counts had declined significantly (p

Intraosseus and extraosseus juxtaarticular calcification: Osteopoikilosis with synovial osteochondromatosis - an association

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Parangama Chatterjee

2009-03-01

Full Text Available

Osteopoikilosis presents as round or ovoid sclerotic lesions with an appearance like enostosis on pathology. Synovial osteochondromatosis occurs due to cartilaginous metaplasia with synovial villous proliferation with calcified nodules in proximity to joints. A case of osteopoikilosis associated with synovial osteochondromatosis is described. Intraosseus and juxta osseus sclerotic bone lesions were identified on radiographs and computed tomography in a patient with knee pain. The association of osteopoikilosis with synovial osteochondromatosis is rare and to our knowledge has received little attention in the literature.

Extensor and flexor digit synovial sheath, sac and synovial capsule in the distal part of the limbs in buffalos and camels and its relation of surgical interference

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S. AL-sadi

2010-01-01

Full Text Available Sixty one samples of the distal parts of limbs were obtained from different ages of buffalo and camels of both sex to study the synovial structures to determine the suitable sites for injection of surgical interference. The result showed that extensor digit synovial sheath was extend between middle or distal part of metacarpal (metatarsal to the extensor processes and this formed with synovial capsule dorsal pouches which serve in surgical interference. The flexor digit synovial sheath extended to palmar (planter between distal extremity of metacarpal (metatarsal to the middle of second phalanx in buffalo while in camel it extended to the proximal extremity of second phalanx, that sheath was formed with suspensory ligament and sessamoid bone palmar or planter pouches which were serve the surgical interference. Fourth synovial bursa observed situated dorsally between the extensor digit laterals tendon and capsule of fetlock joint, forms site of injection during surgical interference, while the other two synovial bursa were located to palmer (planter between deep flexor tendon and distal sessamoid bone in buffalo while in camel these bursa were located between deep flexor tendon and cartilage of the second phalanx, these bursa were served for surgical interference. The synovial capsule which serve the surgical interference through digit cushion these were shown extended from the claw capsule. The result show that surgical interference was form six pouches in buffalo and eight pouches in camel, which formed by synovial structures and the tissue associated with them.

Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis

International Nuclear Information System (INIS)

Kirkhus, Eva; Smith, Hans-Joergen; Arvidsson, Linda Z.; Larheim, Tore A.; Flatoe, Berit; Hetlevik, Siri O.

2016-01-01

MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juvenile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities. To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with juvenile idiopathic arthritis with focus on disk abnormalities. This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 temporomandibular joints were scored for thickness of abnormally enhancing synovium (synovitis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities. The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovitis and abnormal bone shape (38/92; 41%) and D: No synovitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 patients (63%). Disk abnormalities were found in all categories of juvenile idiopathic arthritis involved temporomandibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category. Disk abnormalities were frequent. Disk displacement also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnormalities were found in joints with bone abnormalities. Attention should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis. (orig.)

Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis

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Kirkhus, Eva; Smith, Hans-Joergen [Oslo University Hospital, Rikshospitalet, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Oslo (Norway); Arvidsson, Linda Z.; Larheim, Tore A. [University of Oslo, Department of Maxillofacial Radiology, Institute of Clinical Dentistry, Oslo (Norway); Flatoe, Berit; Hetlevik, Siri O. [Oslo University Hospital, Rikshospitalet, Department of Rheumatology, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Oslo (Norway)

2016-03-15

MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juvenile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities. To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with juvenile idiopathic arthritis with focus on disk abnormalities. This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 temporomandibular joints were scored for thickness of abnormally enhancing synovium (synovitis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities. The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovitis and abnormal bone shape (38/92; 41%) and D: No synovitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 patients (63%). Disk abnormalities were found in all categories of juvenile idiopathic arthritis involved temporomandibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category. Disk abnormalities were frequent. Disk displacement also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnormalities were found in joints with bone abnormalities. Attention should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis. (orig.)

A case of synovial sarcoma in the submandibular region

International Nuclear Information System (INIS)

Sakata, Chie; Kinoshita, Toshibumi; Kaminou, Toshio; Adachi, Akira; Kinoshita, Fumiko; Ogawa, Toshihide

2005-01-01

Synovial sarcomas are a less common cervical tumor in young patients. We report a 23-year-old man with synovial sarcoma in the submandibular region. T2-weighted MR images demonstrated a mixed-intensity tumor attached to the submandibular gland. T1-weighted MR images revealed a focal area with mildly increased signal intensity, indicating intratumoral hemorrhage. MR images were also useful for visualization of tumor extension. Synovial sarcoma should be considered in the differential diagnosis of well-defined in homogeneous tumors adjacent to the submandibular gland in young adults. (author)

Primary Cystic Pleuropulmonary Synovial Sarcoma Presenting as Recurrent Pneumothorax

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Eric D. Johnson

2017-07-01

Full Text Available Primary pleuropulmonary synovial sarcomas are quite rare, representing 0.1–0.5% of all pulmonary malignancies. We report an entirely cystic monophasic synovial sarcoma in a 25-year-old male who presented with recurrent pneumothorax and no evidence of a mass lesion on imaging. The purpose of this case report is to increase awareness of neoplasms clinically presenting as a pneumothorax with no imagining evidence of a mass-forming lesion and emphasize the significance of fluorescent in situ hybridization testing in nontypical synovial sarcoma cases.

Streptococcus agalactiae: an emerging cause of septic arthritis.

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Louthrenoo, Worawit; Kasitanon, Nuntana; Wangkaew, Suparaporn; Hongsongkiat, Sith; Sukitawut, Waraporn; Wichainun, Ramjai

2014-03-01

Invasive Streptococcus agalactiae infection in nonpregnant women has been reported increasingly worldwide. This study reports the clinical features and outcome of S. agalactiae septic arthritis in Thai patients. The medical records of cases with septic arthritis seen between July 1990 and December 2010 were reviewed. Only those with S. agalactiae were included in this study. From 244 cases of septic arthritis, 38 (15.57%, 13 men and 25 women) were caused by S. agalactiae, with 34 of them (89.48%) occurring between 2008 and 2010. Their mean age was 52.89 (SD, 18.95) years. Twenty-four of the 38 patients (63.16%) had 1 or more underlying disease that might predispose to joint infection. Fever and joint pain were the most common symptoms presented. Eleven cases (28.95%) presented monoarthritis, 15 (39.47%) oligoarthritis, and 12 (31.58%) polyarthritis, with a mean joint involvement of 3.34 (SD, 2.35) joints (range, 1-8). Cellulitis was seen in 27 cases (71.05%). Blood cultures were positive in 31 patients (81.58%). Thirty-five of the 38 synovial fluid specimens obtained were enough for cultures and stain smears, with 24 (68.57%) growing S. agalactiae and 19 (54.29%) showing gram-positive cocci. All isolates were sensitive to penicillin. Ten patients (26.31%) received arthroscopic drainage. The articular outcome was good in 11 patients, fair in 24, and poor in 3. There were no deaths. Streptococcus agalactiae is an emerging cause of septic arthritis in Thai patients. Physicians should be especially aware of this condition in patients presenting with acute oligopolyarthritis and prominent cellulitis.

Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors

International Nuclear Information System (INIS)

Hanly, J.G.; Bresnihan, B.; Hassan, J.; Whelan, A.; Feighery, C.; Moriarty, M.

1985-01-01

Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The in-vitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation. (author)

Synovial Lipomatosis of the Glenohumeral Joint

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Shaul Beyth

2016-01-01

Full Text Available Synovial lipomatosis (also known as lipoma arborescens is a rare and benign lesion affecting synovium-lined cavities. It is characterized by hyperplasia of mature fat tissue in the subsynovial layer. Although the most commonly affected site is the knee joint, rarely additional locations such as tendon sheath and other joints are involved. We present a case of synovial lipomatosis of the glenohumeral joint in a 44-year-old man. The clinical data radiological studies and histopathologic results are described, as well as a review of the current literature.

Synovial Sarcoma-A Rare Tumor of the Larynx

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Ghodrat Mohammadi

2016-05-01

Full Text Available Introduction: Malignant mesenchymal tumors of the larynx are rare. One type of malignant mesenchymal tumor is synovial sarcoma with unknown histogenesis, which occurs predominantly in the lower extremities of young adults. The head and neck region is a relatively rare location. There are few cases of malignant mesenchymal tumors with laryngeal localization in literature.  Case Report: In this report, a new case in a 23-year-old man, which was referred with increasing hoarseness for eight months, and dysphagia, odynophagia, and dyspnea since nearly one year ago, is reported. Indirect laryngoscopy revealed a laryngeal submucosal mass. The patient was operated and the histopathological diagnosis of synovial sarcoma was confirmed by IHC (Immunohistochemisry.  Conclusion:  Synovial sarcoma occurs predominantly in the lower extremities of young adults. Because very few cases of laryngeal synovial sarcoma are reported, every new case will bring some new information about diagnosis and therapy. It is of utmost importance to get to know new aspects and therapeutical modalities of this rare tumor.

Mast cells in rheumatoid arthritis: friends or foes?

Science.gov (United States)

Rivellese, Felice; Nerviani, Alessandra; Rossi, Francesca Wanda; Marone, Gianni; Matucci-Cerinic, Marco; de Paulis, Amato; Pitzalis, Costantino

2017-06-01

Mast cells are tissue-resident cells of the innate immunity, implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). They are present in synovia and their activation has been linked to the potentiation of inflammation in the course of RA. However, recent investigations questioned the role of mast cells in arthritis. In particular, animal models generated conflicting results, so that many of their pro-inflammatory, i.e. pro-arthritogenic functions, even though supported by robust experimental evidence, have been labelled as redundant. At the same time, a growing body of evidence suggests that mast cells can act as tunable immunomodulatory cells. These characteristics, not yet fully understood in the context of RA, could partially explain the inconsistent results obtained with experimental models, which do not account for the pro- and anti-inflammatory functions exerted in more chronic heterogeneous conditions such as RA. Here we present an overview of the current knowledge on mast cell involvement in RA, including the intriguing hypothesis of mast cells acting as subtle immunomodulatory cells and the emerging concept of synovial mast cells as potential biomarkers for patient stratification. Copyright © 2017 Elsevier B.V. All rights reserved.

PhosphoLipid transfer protein (PLTP) exerts a direct pro-inflammatory effect on rheumatoid arthritis (RA) fibroblasts-like-synoviocytes (FLS) independently of its lipid transfer activity

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Deckert, Valérie; Daien, Claire I.; Che, Hélène; Elhmioui, Jamila; Lemaire, Stéphanie; Pais de Barros, Jean-Paul; Desrumaux, Catherine; Combe, Bernard; Hahne, Michael; Lagrost, Laurent; Morel, Jacques

2018-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease with modification of lipids profile and an increased risk of cardiovascular events related to inflammation. Plasma phospholipid transfer protein (PLTP) exerts a lipid transfer activity through its active form. PLTP can also bind to receptors such as ATP-binding cassette transporter A1 (ABCA1). In addition to its role in lipoprotein metabolism and atherosclerosis, the latest advances came in support of a complex role of PLTP in the regulation of the inflammatory response, both with pro-inflammatory or anti-inflammatory properties. The aim of the present study was to decipher the role of PLTP in joint inflammation and to assess its relevance in the context of RA. PLTP expression was examined by western-blot and by immunochemistry. ABCA1 expression was analyzed by flow cytometry. Lipid transfer activity of PLTP and pro-inflammatory cytokines were measured in sera and synovial fluid (SF) from RA patients and controls (healthy subjects or osteoarthritis patients [OA]). FLS were treated with both lipid-transfer active form and inactive form of recombinant human PLTP. IL-8, IL-6, VEGF and MMP3 produced by FLS were assessed by ELISA, and proliferation by measuring 3H-Thymidine incorporation. RA synovial tissues showed higher PLTP staining than OA and PLTP protein levels were also significantly higher in RA-FLS. In addition, RA, unlike OA patients, displayed elevated levels of PLTP activity in SF, which correlated with pro-inflammatory cytokines. Both lipid-transfer active and inactive forms of PLTP significantly increased the production of cytokines and proliferation of FLS. ABCA1 was expressed on RAFLS and PLTP activated STAT3 pathway. To conclude, PLTP is highly expressed in the joints of RA patients and may directly trigger inflammation and FLS proliferation, independently of its lipid transfer activity. These results suggest a pro-inflammatory role for PLTP in RA. PMID:29565987

Synovial sarcoma: a rare presentation of parapharyngeal mass.

Science.gov (United States)

Shaariyah, Mohd Mokhtar; Mazita, Ami; Masaany, Mansor; Razif, Mohd Yunus; Isa, Mohamed Rose; Asma, Abdullah

2010-06-01

Synovial sarcoma is a rare soft tissue sarcoma of the head and neck region involving the parapharyngeal space. The diagnosis of synovial sarcoma can be very challenging to the pathologists. We present a rare case of parapharyngeal synovial sarcoma in a young female patient who had a two-month history of left cervical intumescent mass at level II. The fine needle aspiration cytology of the mass was proved inconclusive. Transcervical excision of the mass was performed and the first case of parapharyngeal sarcoma was identified in our center by fluorescence in situ hybridization (FISH) technique. Repeat imaging revealed residual tumor. The patient successfully underwent a second excision of the residual tumor and received adjuvant radiotherapy.

Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis

Science.gov (United States)

Fan, Tingting; Zhang, Changsong; Zong, Ming; Fan, Lieying

2018-01-01

Impaired apoptosis of rheumatoid arthritis (RA)-fibroblast-like synoviocytes (FLS) is pivotal in the process of RA. Peptidyl arginine deiminase type IV (PADI4) is associated with autoantibody regulation via histone citrullination in RA. The present study aimed to investigate the role of PADI4 in the apoptosis of RA-FLS. FLS were isolated from patients with RA and a rat model. The effects of PADI4 on RA-FLS were investigated in vitro and in vivo. Hypoxia-induced autophagy was induced by 1% O2 and was detected by immunohistochemical and immunofluorescence analysis; in addition, apoptosis was detected by flow cytometry. RA-FLS obtained from RA rat model exhibited significant proliferation under severe hypoxia conditions. Hypoxia also significantly induced autophagy and elevated the expression of PADI4. Subsequently, short hairpin RNA-mediated PADI4 knockdown was demonstrated to significantly inhibit hypoxia-induced autophagy and promote apoptosis in RA-FLS. The results of these in vitro and in vivo studies suggested that PADI4 may be closely associated with hypoxia-induced autophagy, and the inhibition of hypoxia-induced autophagy by PADI4 knockdown may contribute to an increase in the apoptosis of RA-FLS. PMID:29393388

Toward understanding the role of cartilage particulates in synovial inflammation.

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Silverstein, A M; Stefani, R M; Sobczak, E; Tong, E L; Attur, M G; Shah, R P; Bulinski, J C; Ateshian, G A; Hung, C T

2017-08-01

Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium. In this study sub-10 μm cartilage particles or 1 μm latex particles were co-cultured with FLS ±10 ng/mL interleukin-1α (IL-1α) or tumor necrosis factor-α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen, and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy. Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups. The proliferative response of FLS to cartilage wear particles resulted in an overall increase in extracellular matrix (ECM) content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Anti-Arthritic Effect of Chebulanin on Collagen-Induced Arthritis in Mice.

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Yinglan Zhao

Full Text Available Rheumatoid arthritis is a chronic degenerative autoimmune disease characterized by persistent inflammation of synovial membranes, which leads to cartilage destruction and bone erosion. To date, there are no effective therapies to slow the progress of this degenerative condition. Here, we evaluate the anti-arthritic effect of chebulanin, an abundant anti-inflammatory agent isolated from Terminalia chebula, in collagen induced arthritis in DBA/1 mice by intragastric administration. Arthritic severity was scored by performing histopathological evaluation of the joints and measuring the expression of inflammatory cytokines and relative enzymes by immunohistochemical staining. In parallel, bone destruction and erosion were confirmed by micro-CT. Our data revealed that chebulanin significantly improved the severity of arthritis. Specifically, the histopathological characteristics of the tissues were improved and expression of TNF-α, IL-6, MMP-3 and COX-2 in the paws and joints of the treated mice decreased in a dose-dependent manner compared with control mice. Furthermore, micro-CT analysis revealed that chebulanin induced a dose-dependent reduction in cartilage destruction and bone erosion. Taken together, our findings suggest that chebulanin suppresses the expression of inflammatory mediators and prevents cartilage destruction and bone erosion in mice. Therefore, chebulanin is a strong therapeutic alternative for the treatment of RA.

Macrophage specific MRI imaging for antigen induced arthritides. A potential new strategy for the diagnosis of rheumatoid arthritis

International Nuclear Information System (INIS)

Simon, G.H.; Rummeny, E.J.; Daldrup-Link, H.E.

2007-01-01

The present work describes the potential of iron oxides for the detection of macrophages in synovitis in experimental, antigen-induced arthritis. The pivotal role of macrophages in rheumatoid arthritis (RA) in humans and in antigen-induced arthritis (AIA) in animal models is discussed. The latter appear to be very similar in many aspects to the human RA. We show the potential for iron oxide-enhanced magnetic resonance imaging (MRI) to determine the macrophage content in the arthritic synovial membranes. The results of our own research, as well as those of other research groups, are presented and discussed. MRI after the intravenous (i.v.) administration of iron oxides enables the depiction of macrophage content in arthritic synovial membranes in AIA through the effects of the intracellular compartmentalisation of iron oxide particles. These effects can be demonstrated in 24-h delayed images after i.v. contrast application, on T2-weighted spin-echo or turbo-spin-echo sequences, and especially on T2 * -weighted gradient-echo sequences. The signal effects are not only apparent in high field strength (4.7 Tesla) but also on 1.5 Tesla clinical scanners. The use of iron oxides enables the determination of the macrophage content in synovitis in animals with AIA. This parameter represents a potential marker to determine disease activity, and possibly represents a marker to evaluate the effectiveness of specific therapies in human RA. Current knowledge of iron oxide-enhanced MRI is limited to animal models. The clinical evaluation of this new method in patients with RA has not yet been performed. However, based on the considerations presented here, significant progress in the diagnostic work-up of RA can be expected

Synovial osteochondromatosis of the temporomandibular joint; Osteocondromatosis sinovial en la articulacion temporomandibular

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Nemnon, Jorge; Nemnon, Marcelo; Staffieri, Roberto; Villavicencio, C; Marconi, G; Masjoan, Diego [Fundacion Villavicencio, Rosario (Argentina). Diagnostico Medico

2004-07-01

Synovial osteochondromatosis (SO) is a meta plastic process by which synovial mesenchymal cells transform into chondroblasts and chondrocytes. This disease affects most frequently the knee, the hip, the elbow, and uncommonly the temporomandibular joint (TMJ). The authors present 2 cases of synovial osteochondromatosis of the TMJ. (author)

Synovial chondromatosis of the elbow in a child

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Rishi Narasimhan

2011-01-01

Full Text Available Synovial chondromatosis is cartilaginous metaplasia of mesenchymal remnants of synovial tissue of the joints. Its main characteristic is the formation of cartilaginous nodules in the synovium and inside the articular space (loose bodies. It usually presents between the third and fifth decades and is rare in children. It presents as a mono-articular pathology affecting large joints such as the knee, hip, and elbow. The main symptoms are pain, swelling, and limitation of movements in the affected joint. Diagnosis is made by panoramic radiographs, computed tomography scan, and mainly magnetic resonance imaging and on surgery. The authors describe of synovial chondromatosis presenting in the elbow of an 11 year-old girl which is unreported to the best of our knowledge.

Osteochondroma and synovial chondromatosis of the temporomandibular joint

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Kim, Sung Eun; Kim, Jae Duk [College of Dentistry, Chosun University, Gwangju (Korea, Republic of)

2002-03-15

Osteochondroma is a benign lesion of osseous and cartilagenous origin. It is a relatively common benign tumor of the skeleton, occurring most often in the metaphyseal region of long bone. However, it is rare in the facial bones. Reported foci in the mandible were the condyle, coronoid process, and symphysis region. Synovial chondromatosis is an uncommon benign condition of unknown etiology which affects the articular joints. Foci of cartilage develop through metaplasia in the underlying connective tissue of the synovial membrane. These cartilagenous foci and fragments may undergo calcification and ossification. We experienced 4 patients with abnormal appearance of mandibular condyle. This report describes 3 cases of osteocondroma and 1 case of synovial chondromatosis of the mandibular condyle with review of the literature

Tamaractam, a New Bioactive Lactam from Tamarix ramosissima, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

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Yao, Yao; Jiang, Cheng-Shuai; Sun, Na; Li, Wei-Qi; Niu, Yang; Han, Huai-Qin; Miao, Zhen-Hua; Zhao, Xun-Xia; Zhao, Jing; Li, Juan

2017-01-10

Chemical investigation of Tamarix ramosissima Ledeb, a traditional herbal medicine used for rheumatoid arthritis (RA) treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam ( 1 ), together with the previously reported compounds cis - N -feruloyl-3- O -methyldopamine ( 2 ) and trans - N -feruloyl-3- O -methyldopamine ( 3 ). The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, as well as comparison with the literature data. The effects of the three compounds on the viability of RA fibroblast-like synoviocytes (RA-FLS) were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2- H -tetrazolium bromide (MTT) assay. Pro-apoptosis effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, activated caspase-3/7 level assessment using luminescence assay, and sub-G₁ fraction measurement using flow cytometry. It was found that these three compounds displayed variable proliferation inhibitory activity in RA-FLS, and compound 1 exhibited the strongest effect. Compound 1 could remarkably induce cellular apoptosis of RA-FLS, increase activated caspase-3/7 levels, and significantly increase sub-G₁ fraction in the cell cycle. The results suggested that compound 1 may inhibit the proliferation of RA-FLS through apoptosis-inducing effect, and these compounds may contribute to the anti-RA effect of T. ramosissima .

Tamaractam, a New Bioactive Lactam from Tamarix ramosissima, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

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Yao Yao

2017-01-01

Full Text Available Chemical investigation of Tamarix ramosissima Ledeb, a traditional herbal medicine used for rheumatoid arthritis (RA treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam (1, together with the previously reported compounds cis-N-feruloyl-3-O-methyldopamine (2 and trans-N-feruloyl-3-O-methyldopamine (3. The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS and 1D and 2D-NMR experiments, as well as comparison with the literature data. The effects of the three compounds on the viability of RA fibroblast-like synoviocytes (RA-FLS were assessed by 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT assay. Pro-apoptosis effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL assay, activated caspase-3/7 level assessment using luminescence assay, and sub-G1 fraction measurement using flow cytometry. It was found that these three compounds displayed variable proliferation inhibitory activity in RA-FLS, and compound 1 exhibited the strongest effect. Compound 1 could remarkably induce cellular apoptosis of RA-FLS, increase activated caspase-3/7 levels, and significantly increase sub-G1 fraction in the cell cycle. The results suggested that compound 1 may inhibit the proliferation of RA-FLS through apoptosis-inducing effect, and these compounds may contribute to the anti-RA effect of T. ramosissima.

Imaging appearances of synovial plicae syndrome of the knee

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Osama Abdalla Mabrouk Kheiralla

2016-08-01

Full Text Available Synovial plicae are synovial folds that may be found as intraarticular structures within the knee joint. They are remnants of incomplete resorption of mesenchymal tissue during fetal development. Synovial plicae, if present, are supposed to be non-pathological and asymptomatic, however if they are exposed to special events like direct trauma or repeated activities, they may be inflamed and become fibrosed and rigid and irritates the synovium of the underlying femoral condyle resulting in secondary mechanical synovitis and chondromalacia leading to what is known as plica syndrome of the knee. Inspite plica syndrome is always suspected on clinical bases and can be clearly visualized by arthroscopic application, still diagnostic imaging by MRI, CT scan and Sonography play important role in the evaluation and diagnosis of this pathological condition. The aim of this article is to provide an overview of the imaging appearances of synovial plicae syndrome of the knee on ultrasound, magnetic resonance imaging (MRI and computerized tomography scan (CT scan.

Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

LENUS (Irish Health Repository)

Rooney, Terence

2012-02-01

OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

Synovial sarcoma mimicking benign peripheral nerve sheath tumor

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Larque, Ana B.; Nielsen, G.P.; Chebib, Ivan [Massachusetts General Hospital and Harvard Medical School, Department of Pathology, Boston, MA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States)

2017-11-15

To assess the radiographic and clinicopathologic features of synovial sarcoma of the nerve that were clinically or radiologically interpreted as benign peripheral nerve sheath tumor. Five patients with synovial sarcoma arising from the peripheral nerve and interpreted clinically and radiologically as peripheral nerve sheath tumors were identified. Clinicopathologic and imaging features were evaluated. There were three females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular bundle. On histologic examination, most tumors were monophasic synovial sarcoma (4/5). At the time of surgery, all tumors were noted to arise along or within a peripheral nerve. All patients were alive with no evidence of disease with median follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign peripheral nerve sheath tumors of the extremities were identified during the same time period. Primary synovial sarcoma of the nerve can mimic peripheral nerve sheath tumors clinically and on imaging and should be included in the differential diagnosis for tumors arising from peripheral nerves. (orig.)

Primary Synovial Sarcoma of External Auditory Canal: A Case Report.

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Devi, Aarani; Jayakumar, Krishnannair L L

2017-07-20

Synovial sarcoma is a rare malignant tumor of mesenchymal origin. Primary synovial sarcoma of the ear is extremely rare and to date only two cases have been published in English medical literature. Though the tumor is reported to have an aggressive nature, early diagnosis and treatment may improve the outcome. Here, we report a rare case of synovial sarcoma of the external auditory canal in an 18-year-old male who was managed by chemotherapy and referred for palliation due to tumor progression.

Synovial hemangiomas of the knee: magnetic resonance findings in six cases

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Concepcion, L.; Marti-Bonmati, L. M.; Dosda, R.; Llauger, J.; Palmer, J.; Mellado, J. M.

1999-01-01

The synovial hemangioma is an uncommon benign vascular tumor that is difficult to diagnose on the basis of clinical signs Moreover, it has no characteristic radiographic features. The objective of the present report was to describe the MR findings associated with synovial hemangioma of the knee. We review the clinical and MR findings in six patients, with histologically confirmed synovial hemangioma of the Knee, studied with different MR systems and techniques. Synovial hemangiomas were isointense with respect to muscle in T1-weighted images, strongly hyperintense in T2-weighted sequences and presented wavy hypointense linear images. Gadolinium administration resulted in a marked enhancement, although it was heterogeneous in two of three cases analyzed. Although the findings are not pathognomonic, the presence of an intraarticular tumor of the knee that is isointense with respect to muscle in T1 and hyperintense in T2, and shows wavy hypointense images and a marked contrast uptake, may suggest the presence of synovial hemangioma. (Author) 11 refs

[New therapies for rheumatoid arthritis].

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Salgado, Eva; Maneiro, José Ramón

2014-11-18

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage and bone. Advances in the knowledge of disease pathogenesis allowed the identification of novel therapeutic targets such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6 or the system JAK/STAT phosphorylation. At present there are 5 TNF antagonists approved for RA. Tocilizumab blocks the pathway of IL-6 and is the only biological with proven efficacy in monotherapy. Rituximab modulates B cell response in RA. Abatacept provided new data on T cell involvement in the pathogenesis of RA. Tofacitinib is the first kinase inhibitor approved for this disease. Biologic drugs have proven efficacy, almost always in combination with methotrexate, and even halt radiographic progression. Monitoring infection is the main precaution in handling these patients. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents.

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Susanne Lindquist

Full Text Available OBJECTIVE: The present study aimed to explore the hypothesis that bile salt-stimulated lipase (BSSL, in addition to being a key enzyme in dietary fat digestion during early infancy, plays an important role in inflammation, notably arthritis. METHODS: Collagen-induced arthritis (CIA and pristane-induced arthritis (PIA in rodents are commonly used experimental models that reproduce many of the pathogenic mechanisms of human rheumatoid arthritis, i.e. increased cellular infiltration, synovial hyperplasia, pannus formation, and erosion of cartilage and bone in the distal joints. We used the CIA model to compare the response in BSSL wild type (BSSL-WT mice with BSSL-deficient 'knock-out' (BSSL-KO and BSSL-heterozygous (BSSL-HET littermates. We also investigated if intraperitoneal injection of BSSL-neutralizing antibodies affected the development or severity of CIA and PIA in mice and rats, respectively. RESULTS: In two consecutive studies, we found that BSSL-KO male mice, in contrast to BSSL-WT littermates, were significantly protected from developing arthritis. We also found that BSSL-HET mice were less prone to develop disease compared to BSSL-WT mice, but not as resistant as BSSL-KO mice, suggesting a gene-dose effect. Moreover, we found that BSSL-neutralizing antibody injection reduced both the incidence and severity of CIA and PIA in rodents. CONCLUSION: Our data strongly support BSSL as a key player in the inflammatory process, at least in rodents. It also suggests the possibility that BSSL-neutralizing agents could serve as a therapeutic model to reduce the inflammatory response in humans.

Giant primary synovial sarcoma of the anterior mediastinum: A case ...

African Journals Online (AJOL)

2015-06-11

Jun 11, 2015 ... We present a case of primary monophasic synovial sarcoma of the anterior ... Here, we report a case of ... fatigue and anorexia, but no weight loss. ..... Primary intrathoracic synovial sarcoma: A clinicopathologic study of. 40 t (X ...

Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

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Ishikawa, Jun; Takahashi, Nobunori; Matsumoto, Takuya; Yoshioka, Yutaka; Yamamoto, Noriyuki; Nishikawa, Masaya; Hibi, Hideharu; Ishigro, Naoki; Ueda, Minoru; Furukawa, Koichi; Yamamoto, Akihito

2016-02-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA. Copyright © 2015 Elsevier Inc. All rights reserved.

Magnetic resonance imaging of the wrist in rheumatoid arthritis: demonstration of progression between 1 and 6 years

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Stewart, Neal R. [Auckland Hospital, Department of Radiology, Private Bag 92024, Auckland (New Zealand); Auckland Radiology Group, Auckland (New Zealand); Crabbe, Jeffrey P. [Auckland Radiology Group, Auckland (New Zealand); McQueen, Fiona M. [Auckland Hospital, Department of Rheumatology, Auckland (New Zealand)

2004-12-01

To describe the changes seen in the wrist in rheumatoid arthritis (RA) on magnetic resonance (MR) imaging obtained at 1 year and 6 years. A cohort of patients with RA has been studied prospectively from symptom onset. MR scans of the dominant wrist in 31 patients obtained at 1 year and 6 years were compared for bone erosions, marrow signal change (oedema), synovial thickness and tenosynovitis. Twenty-two patients had an increase in erosion score in the interval and three patients showed a decrease in erosion score suggesting erosion healing. Fourteen patients had an increase in oedema score in the interval and eight patients had a decrease in oedema score. Synovial thickness increased in 13 patients and decreased in eight. Tenosynovitis increased in 15 patients and decreased in five. Bone erosions developed immediately adjacent to the tenosynovitis in two patients. MR imaging is useful in following the progress of bone erosions, marrow oedema, synovitis and tenosynovitis in RA. (orig.)

Magnetic resonance imaging of the wrist in rheumatoid arthritis: demonstration of progression between 1 and 6 years

International Nuclear Information System (INIS)

Stewart, Neal R.; Crabbe, Jeffrey P.; McQueen, Fiona M.

2004-01-01

To describe the changes seen in the wrist in rheumatoid arthritis (RA) on magnetic resonance (MR) imaging obtained at 1 year and 6 years. A cohort of patients with RA has been studied prospectively from symptom onset. MR scans of the dominant wrist in 31 patients obtained at 1 year and 6 years were compared for bone erosions, marrow signal change (oedema), synovial thickness and tenosynovitis. Twenty-two patients had an increase in erosion score in the interval and three patients showed a decrease in erosion score suggesting erosion healing. Fourteen patients had an increase in oedema score in the interval and eight patients had a decrease in oedema score. Synovial thickness increased in 13 patients and decreased in eight. Tenosynovitis increased in 15 patients and decreased in five. Bone erosions developed immediately adjacent to the tenosynovitis in two patients. MR imaging is useful in following the progress of bone erosions, marrow oedema, synovitis and tenosynovitis in RA. (orig.)

Subchondral synovial cysts (intra-osseous ganglion)

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Graf, L.; Freyschmidt, J.

1988-01-01

Twelve cases of subchondral synovial cysts (intra-osseous ganglion) have been seen and their clinical features, radiological findings and differential diagnosis are described. The lesion is a benign cystic tumour-like mass in the subchondral portion of a synovial joint. Our findings in respect of age, sex and localisation are compared with those of other authors. The aetiology and pathogenesis of the lesion is not completely understood. There is an increased incidence in middle life and joints with high dynamic and static stress are favoured, particularly in the lower extremities. Chronic stress or microtrauma, causing damage to the involved joint, therefore appears to be a plausible explanation. (orig.) [de

Insight into the Endocrine System and the Immune System: A Review of the Inflammatory Role of Prolactin in Rheumatoid Arthritis and Psoriatic Arthritis

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Man W. Tang

2017-06-01

Full Text Available Rheumatoid arthritis (RA is a chronic autoimmune disease that affects females three times more frequently than males. A potential role for hormones, such as prolactin (PRL, may in part explain this phenomenon. The risk of developing RA is increased in women who are lactating after the first pregnancy, which might be related to breastfeeding and the release of PRL. Other studies found a protective effect of PRL on RA development. Some studies have reported that hyperprolactinemia is more common in RA and serum PRL levels are correlated with several disease parameters, although others could not confirm these findings. Overall the plasma PRL levels are on average not elevated in RA. Previously, a small number of open-label clinical trials using bromocriptine, which indirectly decreases PRL levels, were performed in RA patients and showed clinical benefit, although others found the opposite effect. Locally produced PRL at the site of inflammation may have a crucial role in RA as well, as it has been shown that PRL can be produced by synovial macrophages. Locally produced PRL has both pro-inflammatory and anti-inflammatory effects in arthritis. Psoriatic arthritis (PsA is also an autoinflammatory disease, in which the prolactin receptor is also expressed in macrophages. The aim of this review is to provide an overview of the potential role of PRL signaling in inflammatory joint diseases (RA and PsA and its potential as a therapeutic target.

Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory and Th1 responses.

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Gonzalez-Rey, Elena; Chorny, Alejo; Del Moral, Raimundo G; Varela, Nieves; Delgado, Mario

2007-05-01

Rheumatoid arthritis is a chronic autoimmune disease of unknown aetiology characterised by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. To propose a new strategy for the treatment of arthritis based on the administration of cortistatin, a newly discovered neuropeptide with anti-inflammatory actions. DBA/1J mice with collagen-induced arthritis were treated with cortistatin after the onset of disease, and the clinical score and joint histopathology were evaluated. Inflammatory response was determined by measuring the levels of various inflammatory mediators (cytokines and chemokines) in joints and serum. T helper cell type 1 (Th1)-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with collagen and by assaying the content of serum autoantibodies. Cortistatin treatment significantly reduced the severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of cortistatin was associated with a striking reduction in the two deleterious components of the disease-that is, the Th1-driven autoimmune and inflammatory responses. Cortistatin downregulated the production of various inflammatory cytokines and chemokines, decreased the antigen-specific Th1-cell expansion, and induced the production of regulatory cytokines, such as interleukin 10 and transforming growth factor beta1. Cortistatin exerted its effects on synovial cells through both somatostatin and ghrelin receptors, showing a higher effect than both peptides protecting against experimental arthritis. This work provides a powerful rationale for the assessment of the efficacy of cortistatin as a novel therapeutic approach to the treatment of rheumatoid arthritis.

Osteoarthritis and rheumatoid arthritis pannus have similar qualitative metabolic characteristics and pro-inflammatory cytokine response.

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Furuzawa-Carballeda, J; Macip-Rodríguez, P M; Cabral, A R

2008-01-01

Pannus in osteoarthritis (OA) has only recently been characterized. Little is known, however, regarding the behavior of OA pannus in vitro compared to rheumatoid arthritis (RA) pannus. The purpose of our study was to compare OA with RA pannus. Pannus and synovial tissue co-cultures from 5 patients with OA and 5 patients with RA obtained during arthroplasty were studied. Pannus was defined as the microscopic invasive granulation tissue covering the articular surface. Tissues were cultured for 7 days and stained with Alcian Blue technique. Interleukin-1beta (IL-1beta), IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were also determined in supernatants by ELISA. Cartilage oligomeric matrix protein (COMP), type II collagen, TNF-alpha, IL-10 and Ki-67 expression were also detected by immunohistochemistry. All patients had vascular or fibrous pannus. Synovial proliferation, inflammatory infiltrates and a decrease of extracellular matrix proteins were observed in all tissue samples. Chondrocyte proliferation was lower in OA than RA cartilage. OA synovial tissue expressed lower levels of proteoglycans than RA synoyium. Type II collagen levels were lower in OA than in RA cartilage. Significantly higher levels of IL-1beta were found in the supernatants of RA pannus compared to OA pannus (ppannus supernatants. IL-10, IL-12 and IFN-gamma were undetectable. RA and OA pannus had similar pro-inflammatory and anti-inflammatory cytokine profile expression. OA cartilage, synovial tissue and pannus had lower production of proteoglycans, type II collagen and IL-1beta. It remains to be elucidated why OA pannus invades the cartilage surface but does not cause the marginal erosions typically seen in RA.

Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study.

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Martin Andersen

Full Text Available The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD were associated with the individual's mediator production in explants obtained at baseline.RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-, colour Doppler ultrasound (CDUS and 3 Tesla RA magnetic resonance imaging scores (RAMRIS. Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6, monocyte chemo-attractive protein-1 (MCP-1 and macrophage inflammatory protein-1-beta (MIP-1b were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant.16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04, and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03, CDUS (ρ = 0.53, P = 0.04 and bone marrow oedema (ρ = 0.56, P = 0.03 at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.

Monophasic Synovial Sarcoma Presenting as Mitral Valve Obstruction

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Chokesuwattanaskul, Warangkana; Terrell, Jason; Jenkins, Leigh Ann

2010-01-01

We report the case of a 26-year-old man who experienced progressive left-sided chest pain and 2 episodes of near-syncope. Studies revealed a 15-cm mass in the upper left lung, a 10-cm mass in the medial base of the left lung, and a 5-cm left atrial mass that involved the left lung, infiltrated the left pulmonary vein, and prolapsed into the mitral valve, causing intermittent obstruction. The patient underwent surgical excision of the left atrial tumor. Pathologic evaluation confirmed the diagnosis of monophasic synovial sarcoma. To our knowledge, this is only the 3rd report of left atrial invasion and resultant mitral valve obstruction from a synovial sarcoma that infiltrated the pulmonary vein. We believe that this is the 1st documented case of a metastatic left atrial synovial sarcoma in monophasic form. PMID:20844626

X-ray, CT and MRI findings of synovial tuberculosis in joints

International Nuclear Information System (INIS)

Yu Jinghong; Tao Meili; You Zhuangzhi; Yu Huazhi

2006-01-01

Objective: To analyze the X-ray, CT and MRI findings of synovial tuberculosis, and to evaluate the role of MRI in diagnosing synovial tuberculosis. Methods: Fourteen cases of synovial tuberculosis comfirmed by operation and pathology were retrospectively analyzed and summarized. All patients were examined by MRI and X-ray, and CT scans were performed in 3 cases. Results: X-ray showed joint swelling (8 cases), articular space narrowing (7 cases), marginal joint erosions (4 cases), and periarticular osteoporosis (9 cases). The joint swelling was detected on CT in all 3 cases, and bony erosion and speckled sequestra were seen in 2 cases. MRI in all of patients showed joint swelling and synovial proliferation in different drgees, demonstrated as heterogeneously low signal on T 1 WI and slight high signal (7 cases) and obvious high signal (6 cases) on T 2 WI, and diffuse synovial proliferation was demonstrated as massive and nodular signal in 8 cases. Joint effusion was present in 7 cases as low signal on T 1 WI and high signal on T 2 WI. Osseous erosion lesions were seen in 7 cases, and intra-articular cartilage thinned, partly or mostly disappeared in 11 cases. Periarticular bone marrow edema was found in 7 cases. Conclusion: MRI was superior to X-ray and CT in the diagnosis and differential diagnosis of synovial tuberculosis. (authors)

Synovial fluid lubrication of artificial joints: protein film formation and composition.

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Fan, Jingyun; Myant, Connor; Underwood, Richard; Cann, Philippa

2012-01-01

Despite design improvements, wear of artificial implants remains a serious health issue particularly for Metal-on-Metal (MoM) hips where the formation of metallic wear debris has been linked to adverse tissue response. Clearly it is important to understand the fundamental lubrication mechanisms which control the wear process. It is usually assumed that MoM hips operate in the ElastoHydrodynamic Lubrication (EHL) regime where film formation is governed by the bulk fluid viscosity; however there is little experimental evidence of this. The current paper critically examines synovial fluid lubrication mechanisms and the effect of synovial fluid chemistry. Two composition parameters were chosen; protein content and pH, both of which are known to change in diseased or post-operative synovial fluid. Film thickness and wear tests were carried out for a series of model synovial fluid solutions. Two distinct film formation mechanisms were identified; an adsorbed surface film and a high-viscosity gel. The entrainment of this gel controls film formation particularly at low speeds. However wear of the femoral head still occurs and this is thought to be due primarily to a tribo-corrosion mechanisms. The implications of this new lubrication mechanism and the effect of different synovial fluid chemistries are examined. One important conclusion is that patient synovial fluid chemistry plays an important role in determining implant wear and the likelihood of failure.

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation

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Nakanishi, Hirofumi; Araki, Nobuhito [Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-Ku, 537-8511, Osaka (Japan); Sawai, Yuka [Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Kudawara, Ikuo [Department of Orthopedic Surgery, Osaka National Hospital, Osaka (Japan); Mano, Masayuki; Ishiguro, Shingo [Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ueda, Takafumi; Yoshikawa, Hideki [Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka (Japan)

2003-12-01

To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging. (orig.)

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation

International Nuclear Information System (INIS)

Nakanishi, Hirofumi; Araki, Nobuhito; Sawai, Yuka; Kudawara, Ikuo; Mano, Masayuki; Ishiguro, Shingo; Ueda, Takafumi; Yoshikawa, Hideki

2003-01-01

To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging. (orig.)

Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxia-induced mitochondrial mutagenesis in inflammatory arthritis

LENUS (Irish Health Repository)

Biniecka, Monika

2011-07-25

Abstract Introduction To examine the effects of tumour necrosis factor (TNF) blocking therapy on the levels of early mitochondrial genome alterations and oxidative stress. Methods Eighteen inflammatory arthritis patients underwent synovial tissue oxygen (tpO2) measurements and clinical assessment of disease activity (DAS28-CRP) at baseline (T0) and three months (T3) after starting biologic therapy. Synovial tissue lipid peroxidation (4-HNE), T and B cell specific markers and synovial vascular endothelial growth factor (VEGF) were quantified by immunohistochemistry. Synovial levels of random mitochondrial DNA (mtDNA) mutations were assessed using Random Mutation Capture (RMC) assay. Results 4-HNE levels pre\\/post anti TNF-α therapy were inversely correlated with in vivo tpO2 (P < 0.008; r = -0.60). Biologic therapy responders showed a significantly reduced 4-HNE expression (P < 0.05). High 4-HNE expression correlated with high DAS28-CRP (P = 0.02; r = 0.53), tender joint count for 28 joints (TJC-28) (P = 0.03; r = 0.49), swollen joint count for 28 joints (SJC-28) (P = 0.03; r = 0.50) and visual analogue scale (VAS) (P = 0.04; r = 0.48). Strong positive association was found between the number of 4-HNE positive cells and CD4+ cells (P = 0.04; r = 0.60), CD8+ cells (P = 0.001; r = 0.70), CD20+ cells (P = 0.04; r = 0.68), CD68+ cells (P = 0.04; r = 0.47) and synovial VEGF expression (P = 0.01; r = 063). In patients whose in vivo tpO2 levels improved post treatment, significant reduction in mtDNA mutations and DAS28-CRP was observed (P < 0.05). In contrast in those patients whose tpO2 levels remained the same or reduced at T3, no significant changes for mtDNA mutations and DAS28-CRP were found. Conclusions High levels of synovial oxidative stress and mitochondrial mutation burden are strongly associated with low in vivo oxygen tension and synovial inflammation. Furthermore these significant mitochondrial genome alterations are rescued following successful anti TNF

Lipid bilayer membranes: Missing link in the comprehension of synovial lubrication?

Science.gov (United States)

Packard, Ross; Cowley, Leonie; Dubief, Yves

2010-03-01

The human body hosts an extremely efficient tribological system in its synovial joints that operate under very low friction and virtually no wear. It has long been assumed that the higher molecular weight molecules present in the synovial fluid (hyaluronic acid, lubricin) are solely responsible for the mechanical properties of joint. Smaller components, unsaturated phospholipids, have a virtually an undefined role, most probably because of the cancellation of their amphiphilic properties ex vivo caused by oxidation. Using experimental observations of multilamellar arrangements in synovial joints, we formulate the assumption that self-assembling structures provide the anisotropy necessary to synovial fluid to resist drainage under normal compression. Our molecular dynamics simulations demonstrate the tremendous mechanical properties of lipid bilayers and also highlight their weakening consistent with modifications resulting from injuries or joint prosthesis.

Serum Matrix Metalloproteinase-3 as a Noninvasive Biomarker of Histological Synovitis for Diagnosis of Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Jian-Da Ma

2014-01-01

Full Text Available Objective. To explore the correlation between matrix metalloproteinase- (MMP- 3 and histological synovitis in rheumatoid arthritis (RA. Methods. Serum MMP-3 of 62 patients with active RA was detected by ELISA. Serial synovial tissue sections from all RA patients, 13 osteoarthritis, and 10 orthopedic arthropathies patients were stained with hematoxylin and eosin and immunohistochemically for MMP-3, CD3, CD20, CD38, CD68, and CD15. Results. The percentage of lining MMP3+ cells was significantly higher in RA patients especially with high grade synovitis and it was significantly correlated with Krenn’s synovitis score r=0.574, P<0.001 and sublining inflammatory cells. Multivariate stepwise linear regression analysis revealed that the association of the percentage of lining MMP3+ cells with activation of synovial stroma, sublining CD68+ macrophages, and CD15+ neutrophils was stronger than other histological indicators. The percentage of lining MMP3+ cells was significantly correlated with serum MMP-3 in RA r=0.656, P<0.001. Serum MMP-3 was higher in RA patients with high grade synovitis than that of low grade synovitis and significantly correlated with synovitis score and activation of synovial stroma subscore (all P<0.05. Conclusion. Serum MMP-3 may be an alternative noninvasive biomarker of histological synovitis and RA diagnosis.

Radiosynovectomy in the treatment of arthritis

International Nuclear Information System (INIS)

Liepe, Knut

2005-01-01

Full text: Radiosynovectomy is a useful therapeutic option that involves radiopharmaceutical injections into joints, especially to treat rheumatoid arthritis. The indications included different kinds of arthritis, such as rheumatoid arthritis, psoriatic arthritis, Bechterew's disease, hemophiliac arthritis, osteoarthritis, but also patients with joint prosthesis and synovial effusion. There are three commercial available radiopharmaceuticals for the treatment: yttrium-90 for the knee (185 to 250 MBq), rhenium-186 for larger joints (shoulder and hip with 111 MBq; elbow, wrist, ankle joint with can also rederbium-169 for smaller joints (acromioclavicular joint with 37 MBq, thumb base and MTP I with 30 MBq, MCP and MTP II-V with 22 MBq, PIP with 18.5 MBq, and DIP with 15 MBq, respectively). Decisive for the treatment is a positive sign for arthritis in the two-phase bone scan with 99mTc-HMDP (high uptake in the blood pool phase). Only for radiosynovecotmy in the knee an ultrasound with an evidence of effusion is sufficient. Side effects by the treatment are rare, such as temporary radiation or crystal synovitis, tissue necrosis (extra articular fraction or intra-articular), joint infection (1 of 35,000 joints) or effects due to the immobilisation (thrombosis, pulmonary embolism (immobilization of the knee), lymphoedema or loss of motion. In the treatment of the knee a prophylaxis with heparin is necessary to protect the patients for a pulmonary embolism. The clinical outcome is depending from the primary disease and the stage of arthrosis. Kresnik at al reported in 2190 treated joints an overall response rate of 73 ± 17%. A higher response rate was observed in patients with early stage of arthrosis (73 ± 12%) to patients with advance stage (52 ± 24%). The best results had patients with hemophiliac arthritis (91 ± 4%). In our hospital were treated up to 10.000 joints with a mean response rate of 70-80%. There was a higher response rate in larger joints with 81 ± 5

Giant primary synovial sarcoma of the anterior mediastinum: A case ...

African Journals Online (AJOL)

Primary synovial sarcoma is a very rare tumor of the mediastinum, which is unreported in the entire subcontinent of West Africa, and presents daunting challenges from diagnosis to management with lack of standard management strategies. We present a case of primary monophasic synovial sarcoma of the anterior ...

Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment

International Nuclear Information System (INIS)

Hanly, J.G.; Hassan, J.; Moriarty, M.; Barry, C.; Molony, J.; Casey, E.; Whelan, A.; Feighery, C.; Bresnihan, B.

1986-01-01

Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis

MRI and ultrasound in children with juvenile chronic arthritis

International Nuclear Information System (INIS)

Lamer, S.; Sebag, G.H.

2000-01-01

In this era of advancing imaging technology, a knowledge of the relative values of available imaging techniques is necessary to optimize the management of children with juvenile chronic arthritis (JCA). After clinical examination, plain films remain the initial investigation. The need for radiation protection must be a priority in children with JCA. Conventional radiographs allow grouping of the various arthritides (on the base of the distribution and pattern of joint space changes) and staging of disease progression. Ultrasound (US) is very sensitive in the detection of joint effusions, especially in the hip, and guides fluid aspiration. US and Doppler can be used for the evaluation of synovial hypertrophy and activity. Arthrography and to a certain extent nuclear studies have been replaced by magnetic resonance imaging (MRI). MRI can demonstrate articular cartilage, joint effusion, synovial hypertrophy, cortical and medullary bone, cartilage and bone perfusion, and fibrocartilaginous structures (menisci and ligaments). Contrast enhanced MRI is the most sensitive modality to determine whether an arthritic condition is present. However, it does not assist in establishing a specific diagnosis. MRI determines accurately the activity and the extent of the disease and is particularly useful in the early detection of articular damage. Finally, MRI is of major importance in the evaluation of response to local therapy (especially steroids) and the detection of complications

Multidrug resistant bacteria isolated from septic arthritis in horses

Directory of Open Access Journals (Sweden)

Rodrigo G. Motta

Full Text Available ABSTRACT: Septic arthritis is a debilitating joint infectious disease of equines that requires early diagnosis and immediate therapeutic intervention to prevent degenerative effects on the articular cartilage, as well as loss of athletic ability and work performance of the animals. Few studies have investigated the etiological complexity of this disease, as well as multidrug resistance of isolates. In this study, 60 horses with arthritis had synovial fluid samples aseptically collected, and tested by microbiological culture and in vitro susceptibility test (disk diffusion using nine antimicrobials belonging to six different pharmacological groups. Bacteria were isolated in 45 (75.0% samples, as follows: Streptococcus equi subsp. equi (11=18.3%, Escherichia coli (9=15.0%, Staphylococcus aureus (6=10.0%, Streptococcus equi subsp. zooepidemicus (5=8.3%, Staphylococcus intermedius (2=3.3%, Proteus vulgaris (2=3.3%, Trueperella pyogenes (2=3.3%, Pseudomonas aeruginosa (2=3.3%, Klebsiella pneumoniae (1=1.7%, Rhodococcus equi (1=1.7%, Staphylococcus epidermidis (1=1.7%, Klebsiella oxytoca (1=1.7%, Nocardia asteroides (1=1.7%, and Enterobacter cloacae (1=1.7%. Ceftiofur was the most effective drug (>70% efficacy against the pathogens in the disk diffusion test. In contrast, high resistance rate (>70% resistance was observed to penicillin (42.2%, enrofloxacin (33.3%, and amikacin (31.2%. Eleven (24.4% isolates were resistant to three or more different pharmacological groups and were considered multidrug resistant strains. The present study emphasizes the etiological complexity of equine septic arthritis, and highlights the need to institute treatment based on the in vitro susceptibility pattern, due to the multidrug resistance of isolates. According to the available literature, this is the first report in Brazil on the investigation of the etiology. of the septic arthritis in a great number of horses associated with multidrug resistance of the isolates.

Inflammatory cytokines and hypoxia contribute to 18F-FDG uptake by cells involved in pannus formation in rheumatoid arthritis.

Science.gov (United States)

Matsui, Tamiko; Nakata, Norihito; Nagai, Shigenori; Nakatani, Akira; Takahashi, Miwako; Momose, Toshimitsu; Ohtomo, Kuni; Koyasu, Shigeo

2009-06-01

Assessment of the activity of rheumatoid arthritis (RA) is important for the prediction of future articular destruction. (18)F-FDG PET is known to represent the metabolic activity of inflammatory disease, which correlates with the pannus volume measured by MRI or ultrasonography. To evaluate the correlation between (18)F-FDG accumulation and RA pathology, we assessed (18)F-FDG accumulation in vivo using collagen-induced arthritis (CIA) animal models and (3)H-FDG uptake in vitro using various cells involved in arthritis. (18)F-FDG PET images of rats with CIA were acquired on days 10, 14, and 17 after arthritis induction. The specimens were subsequently subjected to macroautoradiography, and the (18)F-FDG accumulation was compared with the histologic findings. (3)H-FDG uptake in vitro in inflammatory cells (neutrophils, macrophages, T cells, and fibroblasts) was measured to evaluate the contributions of these cells to (18)F-FDG accumulation. In addition, the influence on (3)H-FDG uptake of inflammatory factors, such as cytokines (tumor necrosis factor alpha [TNFalpha], interleukin 1 [IL-1], and IL-6), and hypoxia was examined. (18)F-FDG PET depicted swollen joints, and (18)F-FDG accumulation increased with the progression of arthritis. Histologically, a higher level of (18)F-FDG accumulation correlated with the pannus rather than the infiltration of inflammatory cells around the joints. In the in vitro (3)H-FDG uptake assay, fibroblasts showed the highest (3)H-FDG uptake, followed by neutrophils. Although only a small amount of (3)H-FDG was incorporated by resting macrophages, a dramatic increase in (3)H-FDG uptake in both fibroblasts and macrophages was observed when these cells were exposed to inflammatory cytokines, such as TNFalpha and IL-1, and hypoxia. Although neutrophils showed relatively high (3)H-FDG uptake without activation, no increase in (3)H-FDG uptake was observed in response to inflammatory cytokines. (3)H-FDG uptake by T cells was much lower than

Increased amount of phosphorylated proinflammatory osteopontin in rheumatoid arthritis synovia is associated to decreased tartrate-resistant acid phosphatase 5B/5A ratio.

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Jani Luukkonen

Full Text Available Osteopontin (OPN is an immunoregulatory protein which production increases in both rheumatoid arthritis (RA and osteoarthritis (OA. Phosphorylated osteopontin (Phospho-OPN is known to increase macrophage and osteoclast activation, this process is controlled by extracellular tartrate-resistant acid phosphatase (TRAcP, also a biomarker for RA. Here, we evaluated the phosphorylation status of OPN in RA and OA synovia, as well as its correlation with TRAcP isoforms.Synovial tissue and fluid were obtained from 24 RA (14 seropositive and 10 seronegative and 24 OA patients. Western blotting was used to analyze the extent of OPN phosphorylation. TRAcP isoforms were measured in synovial fluid using ELISA; immunohistochemistry assessed the distribution of OPN and TRAcP expressing cells in the synovial tissue, especially distinguishing between the TRAcP isoforms.Full-length OPN was more phosphorylated in RA than in OA (p<0.05. The thrombin cleaved C-terminal end of OPN was also more phosphorylated in RA (p<0.05. RA patients had a lower concentration of TRAcP 5B and higher concentration of less active 5A in their synovial fluid compared to OA patients. The TRAcP 5B/5A ratio was decreased in RA and correlated negatively with the amount of phospho-OPN (p<0.05. TRAcP positive cells for both isoforms were found all along the synovial lining; OPN antibody staining was localized in the extracellular matrix.Our data suggests that in RA the synovial fluid contains insufficient amounts of TRAcP 5B which increase levels of the proinflammatory phospho-OPN. This may lead to increased macrophage and osteoclast activation, resulting in the increased local inflammation and bone resorption present in RA joints.

Intermetatarsal bursa primary synovial chondromatosis. Case report and review of the literature

Energy Technology Data Exchange (ETDEWEB)

Trevino, Manuel; Laks, Shaked; Sundarakumar, Dinesh K.; Smith, Crysela M. [Texas Tech Univ. Health Science Center, El Paso, TX (United States). Dept. of Radiology; Kafchinski, Lisa [Texas Tech Univ. Health Science Center, El Paso, TX (United States). Dept. of Orthopedic Surgery and Rehabilitation

2017-12-15

Primary synovial chondromatosis is a benign neoplastic process, occurring mostly in large joints, more rarely in tendon sheaths, and extremely uncommonly in bursae. We describe a patient with primary synovial chondromatosis arising in the fourth intermetatarsal bursa. Knowledge of the bursal anatomy of the forefoot, and of characteristic imaging findings and the pathogenesis of synovial chondromatosis, is essential in including this uncommon entity in the differential when occurring in unusual locations. (orig.)

Radiosynovectomy in the treatment of arthritis

International Nuclear Information System (INIS)

Liepe, K.

2007-01-01

Full text: Radiosynovectomy is a useful therapeutic option that involves radiopharmaceutical injections into joints, especially to treat rheumatoid arthritis. The indications included different kinds of arthritis, such as rheumatoid arthritis, psoriatic arthritis, Bechterew's disease, hemophiliac arthritis, osteoarthritis, but also patients with joint prosthesis and synovial effusion. There are three commercial available radiopharmaceuticals for the treatment: yttrium-90 for the knee (185 to 250 MBq), rhenium-186 for larger joints (shoulder and hip with 111 MBq; elbow, wrist, ankle joint with 74 MBq) and erbium- 169 for smaller joints (acromioclavicular joint with 37 MBq, thumb base and MTP I with 30 MBq, MCP and MTP II-V with 22 MBq, PIP with 18.5 MBq, and DIP with 15 MBq, respectively). Decisive for the treatment is a positive sign for arthritis in the two-phase bone scan with 99mTc- HMDP (high uptake in the blood pool phase). Only for radiosynovectomy in the knee an ultrasound with an evidence of effusion is sufficient. Side effects by the treatment are rare, such as temporary radiation or crystal synovitis, tissue necrosis (extra-articular fraction or intraarticular), joint infection (1 of 35,000 joints) or effects due to the immobilization (thrombosis, pulmonary embolism (immobilization of the knee), lymph edema or loss of motion. In the treatment of the knee, a prophylaxis with heparin is necessary to protect the patients for pulmonary embolism. The radiation absorbed dose to the patients are low because a low leakage rate from the treated joint (lymphogenic uptake of 1.8%ID (0.45 to 4.78). These leads to a radiation exposure to the testis of 0.1mSv (0.05 to 0.18) and to the ovary of 0.2 mSv (0.1 to 0.38). Significantly is the radiation exposure of the physician, here especially at the finger pulp. A high beta dose of 22.1 μSv/MBq for the forefinger was observed using only a syringe protection in treatments of knees ( 90 Y), this resulted in a annual

Responsiveness in rheumatoid arthritis. a report from the OMERACT 11 ultrasound workshop.

Science.gov (United States)

Iagnocco, Annamaria; Naredo, Esperanza; Wakefield, Richard; Bruyn, George A W; Collado, Paz; Jousse-Joulin, Sandrine; Finzel, Stephanie; Ohrndorf, Sarah; Delle Sedie, Andrea; Backhaus, Marina; Berner-Hammer, Hilde; Gandjbakhch, Frederique; Kaeley, Gurjit; Loeuille, Damien; Moller, Ingrid; Terslev, Lene; Aegerter, Philippe; Aydin, Sibel; Balint, Peter V; Filippucci, Emilio; Mandl, Peter; Pineda, Carlos; Roth, Johannes; Magni-Manzoni, Silvia; Tzaribachev, Niolay; Schmidt, Wolfgang A; Conaghan, Philip G; D'Agostino, Maria-Antonietta

2014-02-01

To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Task Force on the validity of different US measures in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) presented during the OMERACT 11 Workshop. The Task Force is an international group aiming to iteratively improve the role of US in arthritis clinical trials. Recently a major focus of the group has been the assessment of responsiveness of a person-level US synovitis score in RA: the US Global Synovitis Score (US-GLOSS) combines synovial hypertrophy and power Doppler signal in a composite score detected at joint level. Work has also commenced examining assessment of tenosynovitis in RA and the role of US in JIA. The US-GLOSS was tested in a large RA cohort treated with biologic therapy. It showed early signs of improvement in synovitis starting at Day 7 and increasing to Month 6, and demonstrated sensitivity to change of the proposed grading. Subsequent voting questions concerning the application of the US-GLOSS were endorsed by > 80% of OMERACT delegates. A standardized US scoring system for detecting and grading severity of RA tenosynovitis and tendon damage has been developed, and acceptable reliability data were presented from a series of exercises. A preliminary consensus definition of US synovitis in pediatric arthritis has been developed and requires further testing. At OMERACT 11, consensus was achieved on the application of the US-GLOSS for evaluating synovitis in RA; and work continues on development of RA tenosynovitis scales as well as in JIA synovitis.

Psoriatic arthritis: A retrospective study of 162 patients

Directory of Open Access Journals (Sweden)

Pavlica Ljiljana

2005-01-01

-inflammatory drugs, with systemic corticosteroids 41.3% and with disease modified antirheumatic drugs, most frequently methotrexate, 59.9% of the patients. Radionuclide synovectomy was performed in 6.8%, surgery in 6.2% and physical therapy in all the patients. Conclusion. Psoriatic arthritis developed in 9.3% of the psoriatic patients. Time interval for establishing the diagnosis was long, and there were no specific laboratory findings. All the synovial joints could be involved in the psoriatic process. Scintigraphy should be used only in case of early suspected sacroiliitis. The treatment of psoriatic arthritis was the teamwork between the dermatologist, rheumatologist, physiatrist and orthopedic surgeon.

PER2 is downregulated by the LPS-induced inflammatory response in synoviocytes in rheumatoid arthritis and is implicated in disease susceptibility.

Science.gov (United States)

Lee, Hwayoung; Nah, Seong-Su; Chang, Sung-Hae; Kim, Hyung-Ki; Kwon, Jun-Tack; Lee, Sanghyun; Cho, Ik-Hyun; Lee, Sang Won; Kim, Young Ock; Hong, Seung-Jae; Kim, Hak-Jae

2017-07-01

The clinical symptoms of rheumatoid arthritis (RA) present with circadian variation, with joint stiffness and pain more prominent in the early morning. The mammalian clock genes, which include circadian locomotor output cycles kaput, brain and muscle Arnt-like protein 1, period and cryptochrome, regulate circadian rhythms. In order to identify the association between genetic polymorphisms in the circadian clock gene period 2 (PER2) and RA, the present study genotyped three PER2 single nucleotide polymorphisms (SNPs), rs934945, rs6754875, and rs2304674, using genetic information from 256 RA patients and 499 control subjects. Primary cultured rheumatoid synovial cells were stimulated with 10 µM lipopolysaccharide (LPS). Total protein was then extracted from the synovial cells following 12 and 24 h, and PER2 protein expression was assayed by immunoblotting. The rs2304674 SNP demonstrated a significant association with susceptibility to RA following Bonferroni correction. However, statistical analysis indicated that the SNPs were not associated with any clinical features of patients with RA. Immunoblotting analysis demonstrated that PER2 protein expression was decreased by LPS‑induced inflammation in RA synovial cells; however, this was not observed in normal synovial cells. The results suggest that the PER2 gene may be a risk factor for RA, and expression of the PER2 protein may be affected by inflammation. Therefore, PER2 may contribute to the pathogenesis of RA.

Radiological imaging in early diagnosis of rheumatoid arthritis. The role of ultrasound and magnetic resonance imaging; Radiologische Fruehdiagnostik der rheumatoiden Arthritis. Stellenwert von Ultraschall und Magnetresonanztomographie

Energy Technology Data Exchange (ETDEWEB)

Platzgummer, H.; Schueller-Weidekamm, C. [AKH, Medizinische Universitaet Wien, Universitaetsklinik fuer Radiodiagnostik, Wien (Austria)

2012-02-15

For optimal therapy management of patients with rheumatoid arthritis (RA) specific and sensitive diagnostic methods are essential for assessment of disease activity. In addition to projection radiography, imaging techniques, in particular magnetic resonance imaging (MRI) and ultrasound (US) are becoming increasingly more important for the early diagnosis of RA. The MRI and US techniques play a key role in the early imaging diagnostics of RA. Measurement of inflammation activity represents the basis of therapeutic decision-making and can be quantitatively and qualitatively determined with MRI and US. Synovitis and bone marrow edema are predictors of erosion. (orig.) [German] Fuer das optimale Therapiemanagement bei Patienten mit rheumatoider Arthritis (RA) sind spezifische und sensible diagnostische Methoden zur Beurteilung der Krankheitsaktivitaet unerlaesslich. Neben der Projektionsradiographie gewinnen die bildgebenden Methoden zur Fruehdiagnostik der RA, insbesondere die Magnetresonanztomographie (MRT) und der Ultraschall (US), zunehmend an Bedeutung. MRT und US spielen eine Schluesselrolle in der bildgebenden Fruehdiagnostik der RA. Die Messung der Entzuendungsaktivitaet stellt die Basis fuer die Therapieentscheidung dar. Sie kann mit dem US und der MRT quantitativ und semiquantitativ bestimmt werden. Synovialitis und Knochenmarkoedem sind Praediktoren fuer Erosionen. (orig.)

Synovial Tissue Response to Treatment with TNF Blockers in Peripheral Spondyloarthritis

NARCIS (Netherlands)

Paramarta, Jacqueline E.; Baeten, Dominique; de Rycke, Leen

2011-01-01

This review describes the synovial response to treatment in peripheral spondyloarthritis (SpA). A series of recent studies demonstrates that the synovial histopathology is largely homogenous between different SpA subtypes and can be strongly modulated by effective treatment such as tumor necrosis

US Evaluation of Juvenile Idiopathic Arthritis and Osteoarticular Infection.

Science.gov (United States)

Nguyen, Jie C; Lee, Kenneth S; Thapa, Mahesh M; Rosas, Humberto G

2017-01-01

Juvenile idiopathic arthritis (JIA) and osteoarticular infection can cause nonspecific articular and periarticular complaints in children. Although contrast material-enhanced magnetic resonance imaging is the reference standard imaging modality, musculoskeletal ultrasonography (US) is emerging as an important adjunct imaging modality that can provide valuable information relatively quickly without use of radiation or the need for sedation. However, diagnostic accuracy requires a systemic approach, familiarity with various US techniques, and an understanding of maturation-related changes. Specifically, the use of dynamic, Doppler, and/or multifocal US assessments can help confirm sites of disease, monitor therapy response, and guide interventions. In patients with JIA, ongoing synovial inflammation can lead to articular and periarticular changes, including synovitis, tenosynovitis, cartilage damage, bone changes, and enthesopathy. Although these findings can manifest in adult patients with rheumatoid arthritis, important differences and pitfalls exist because of the unique changes associated with an immature and maturing skeleton. In patients who are clinically suspected of having osteoarticular infection, the inability of US to evaluate the bone marrow decreases its sensitivity. Therefore, the US findings should be interpreted with caution because juxtacortical inflammation is suggestive, but neither sensitive nor specific, for underlying osteomyelitis. Similarly, the absence of a joint effusion makes septic arthritis extremely unlikely but not impossible. US findings of JIA and osteoarticular infection often overlap. Although certain clinical scenarios, laboratory findings, and imaging appearances can favor one diagnosis over the other, fluid analysis may still be required for definitive diagnosis and optimal treatment. US is the preferred modality for fluid aspiration and administering intra-articular corticosteroid therapy. © RSNA, 2017.

Photodynamic damage to cartilage and synovial tissue grafted on a chick's chorioallantoic membrane

Science.gov (United States)

Fisher, M.; Nahir, A. M.; Kimel, Sol

1997-09-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints causing pain deformities and disability. The highly vascular inflamed synovium has aggressive and destructive characteristics, it invades, erodes and gradually destroys cartilage and underlying bone. Photodynamic therapy (PDT) was performed using the chick chorioallantoic membrane (CAM) model to investigate the vitality of synovium and cartilage implanted on the CAM. Synovium, obtained from human patients, was grafted onto the CAM; gross microscopy and histology proved its vitality 7 days post grafting. Cartilage obtained from rabbit knee joint was also maintained on the CAM for 7 days. Its vitality was demonstrated by histology and by measuring metabolic and enzymatic activity of cartilage cells (chondrocytes) as well as the collagen and proteoglycans content. Selective PDT was performed using aluminum phthalocyanine tetrasulfonate (AlPcS4), a hydrophilic compound, soluble in biological solutions, as a photosensitizer. After irradiation with a diode laser (lambda equals 670 nm, 10 mW) damage was observed in vascularized synovium grafts, whereas avascular cartilage remained intact.

[Passage of nonsteroidal anti-inflammatory agents across the synovial membrane].

Science.gov (United States)

Netter, P; Bannwarth, B; Monot, C; Royer, R J; Gaucher, A

1983-09-24

The therapeutic effectiveness of non-steroid anti-inflammatory (NSAI) drugs is partly determined by their passage across the synovial membrane. The synovium can be compared to a double barrier the permeability of which to NSAI drugs depends on the degree of inflammation of the joint and on the pharmacokinetic properties of the drugs (lipophilia, pka, protein-binding). A few hours after one single systemic dose, concentrations in the synovial fluid are higher than in serum. During chronic administration, concentrations of NSAI drugs with a short half-life vary less in synovial fluid than in serum. During steady state, free fractions of NSAI drugs with prolonged half-life may be similar in both compartments.

Thoracic Synovial Cyst at the Th2-3 Level Causing Myelopathy

DEFF Research Database (Denmark)

Sundskarð, Martin M; Gaini, Shahin

2017-01-01

Intraspinal synovial cyst is a rare cause of myelopathy. These cysts present most often in the lumbar and cervical parts of the spine but are more infrequent in the thoracic spine. We present a case of a 73-year-old man with an intraspinal, extradural synovial cyst at the Th2-3 level causing...... paraesthesia and weakness in the legs. A laminectomy and excision of the cyst were performed and the patient recovered fully. In the thoracic spine, synovial cysts are almost exclusively found in the lower part. Laminectomy, with excision, is the treatment of choice, although steroid injections have been...

Dual role of interleukin-17 in pannus growth and osteoclastogenesis in rheumatoid arthritis.

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Ito, Hiroshi; Yamada, Hidehiro; Shibata, Toshiko N; Mitomi, Hirofumi; Nomoto, So; Ozaki, Shoichi

2011-02-04

In a murine model, interleukin (IL)-17 plays a critical role in the pathogenesis of arthritis. There are controversies, however, regarding whether IL-17 is a proinflammatory mediator in rheumatoid arthritis (RA). We previously established an ex vivo cellular model using synovial tissue (ST)-derived inflammatory cells, which reproduced pannus-like tissue growth and osteoclastic activity in vitro. Using this model, we investigated the effects of IL-17 on pannus growth and osteoclastogenesis in RA. Inflammatory cells that infiltrated synovial tissue from patients with RA were collected without enzyme digestion and designated as ST-derived inflammatory cells. ST-derived inflammatory cells were cultured in the presence or absence of IL-17 or indomethacin, and the morphologic changes were observed for 4 weeks. Cytokines produced in the culture supernatants were measured by using enzyme-linked immunosorbent assay kits. Osteoclastic activity was assessed by the development of resorption pits in calcium phosphate-coated slides. Exogenous addition of IL-17 dramatically enhanced the spontaneous production of IL-6 and prostaglandin E₂ (PGE₂) by the ST-derived inflammatory cells, while it had no effect on the production of tumor necrosis factor (TNF)-α and macrophage colony-stimulating factor (M-CSF). Furthermore, IL-17 did not affect the spontaneous development of pannus-like tissue growth and osteoclastic activity by the ST-derived inflammatory cells. On the other hand, IL-17 enhanced pannus-like tissue growth, the production of TNF-α and M-CSF and the development of osteoclastic activity in the presence of indomethacin, an inhibitor of endogenous prostanoid production, while exogenous addition of PGE₁ suppressed their activities. The present study suggests that IL-17 induces negative feedback regulation through the induction of PGE₂, while it stimulates proinflammatory pathways such as inflammatory cytokine production, pannus growth and osteoclastogenesis in RA.

Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis

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Kvien Tore K

2007-06-01

Full Text Available Abstract Background The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5Δ32 and rheumatoid arthritis (RA has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA, an association with CCR5 was recently reported. The purpose of this study was to investigate if the CCR5Δ32 polymorphism is associated with RA or JIA in Norwegian cohorts. Methods 853 RA patients, 524 JIA patients and 658 controls were genotyped for the CCR5Δ32 polymorphism. Results The CCR5Δ32 allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR = 0.90; P = 0.36 and 9.7% in JIA patients (OR = 0.85; P = 0.20. No decreased homozygosity was observed for CCR5Δ32, as previously suggested. Conclusion Our data do not support an association between the CCR5Δ32 allele and Norwegian RA or JIA patients. Combining our results with those from a recently published meta-analysis still provide evidence for a role for CCR5Δ32 in RA, albeit substantially weaker than the effect first reported.

Condromatose sinovial Synovial chondromatosis

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Neylor Pace Lasmar

2010-01-01

the site. He was referred to a knee specialist with a suspected meniscal injury. Upon examination, we detected severe swelling of the joint with limitation of motion, pain exacerbated, and negative joint aspiration. Since simple radiographic results were normal, an MRI of the knee was requested. The MRI revealed massive accumulation of synovial fluid, together with marked synovial proliferation, especially focal thickening clumps with intermediate signal on T1 and T2, a hypointense signal on T2, and discreet suggestive of pigmented villonodular synovitis with intact meniscus and ligaments. The patient underwent arthroscopy of the left knee, which revealed whitish irregular fragments, and underwent arthrotomy with removal of the lesion and extensive synovectomy. The material was submitted to pathological examination, which showed the presence of synovial chondromatosis. Eight months after surgery, the patient presents with no complaints, with a 130° range in the left knee without joint bleeding or signs of inflammation. Synovial chondromatosis is a rare benign metaplasia of the synovial membrane, leading to the formation of cartilaginous loose bodies in the joint space. It is difficult to diagnose because 95% of the nodules, when not calcified, can be overlooked radiologically.

Percentages of CD4+CD161+ and CD4−CD8−CD161+ T Cells in the Synovial Fluid Are Correlated with Disease Activity in Rheumatoid Arthritis

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Jinlin Miao

2015-01-01

Full Text Available Objective. CD161 has been identified as a marker of human IL-17-producing T cells that are implicated in the pathogenesis of rheumatoid arthritis (RA. This study aimed to investigate the potential link between the percentage of CD161+ T cells and disease activity in RA patients. Methods. Peripheral blood (PB from 54 RA patients and 21 healthy controls was evaluated. Paired synovial fluid (SF (n = 17 was analyzed. CD161 expression levels on CD4+, CD8+, and CD4−CD8− T cells were assessed by flow cytometry. Results. The percentage of CD4+CD161+ T cells in RA SF was higher than RA PB, and it was positively correlated with DAS28, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP. CD4−CD8−CD161+ T cell percentage was decreased in RA PB and was further reduced in RA SF, and its level in SF was inversely correlated with DAS28, ESR, and CRP. However, CD8+CD161+ T cell percentage was neither changed in RA PB and SF nor correlated with disease activity indices. Conclusion. An increased CD4+CD161+ T cell percentage and a decreased CD4−CD8−CD161+ T cell percentage are present in RA SF and are associated with disease activity, and the accumulation of CD4+CD161+ T cells in SF may contribute to the local inflammation of RA.

Predictive Factors for Differentiating Between Septic Arthritis and Lyme Disease of the Knee in Children.

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Baldwin, Keith D; Brusalis, Christopher M; Nduaguba, Afamefuna M; Sankar, Wudbhav N

2016-05-04

Differentiating between septic arthritis and Lyme disease of the knee in endemic areas can be challenging and has major implications for patient management. The purpose of this study was to identify a prediction rule to differentiate septic arthritis from Lyme disease in children presenting with knee pain and effusion. We retrospectively reviewed the records of patients younger than 18 years of age with knee effusions who underwent arthrocentesis at our institution from 2005 to 2013. Patients with either septic arthritis (positive joint fluid culture or synovial white blood-cell count of >60,000 white blood cells/mm(3) with negative Lyme titer) or Lyme disease (positive Lyme immunoglobulin G on Western blot analysis) were included. To avoid misclassification bias, undiagnosed knee effusions and joints with both a positive culture and positive Lyme titers were excluded. Historical, clinical, and laboratory data were compared between groups to identify variables for comparison. Binary logistic regression analysis was used to identify independent predictive variables. One hundred and eighty-nine patients were studied: 23 with culture-positive septic arthritis, 26 with culture-negative septic arthritis, and 140 with Lyme disease. Multivariate binary logistic regression identified pain with short arc motion, history of fever reported by the patient or a family member, C-reactive protein of >4 mg/L, and age younger than 2 years as independent predictive factors for septic arthritis. A simpler model was developed that showed that the risk of septic arthritis with none of these factors was 2%, with 1 of these factors was 18%, with 2 of these factors was 45%, with 3 of these factors was 84%, or with all 4 of these factors was 100%. Although septic arthritis of the knee and Lyme monoarthritis share common features that can make them difficult to distinguish clinically, the presence of pain with short arc motion, C-reactive protein of >4.0 mg/L, patient-reported history of

Contrast-enhanced MRI compared with the physical examination in the evaluation of disease activity in juvenile idiopathic arthritis

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Hemke, Robert; Maas, Mario; Veenendaal, Mira van; Kuijpers, Taco W.; Dolman, Koert M.; Rossum, Marion A.J. van; Berg, J.M. van den

2014-01-01

To assess the value of magnetic resonance imaging (MRI) in discriminating between active and inactive juvenile idiopathic arthritis (JIA) patients and to compare physical examination outcomes with MRI outcomes in the assessment of disease status in JIA patients. Consecutive JIA patients with knee involvement were prospectively studied using an open-bore MRI. Imaging findings from 146 JIA patients were analysed (59.6 % female; mean age, 12.9 years). Patients were classified as clinically active or inactive. MRI features were evaluated using the JAMRIS system, comprising validated scores for synovial hypertrophy, bone marrow oedema, cartilage lesions and bone erosions. Inter-reader reliability was good for all MRI features (intra-class correlation coefficient [ICC] = 0.87-0.94). No differences were found between the two groups regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions. Synovial hypertrophy scores differed significantly between groups (P = 0.016). Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9 %) with clinically inactive disease. Of JIA patients considered clinically active, 48.6 % showed no signs of MRI-based synovitis. MRI can discriminate between clinically active and inactive JIA patients. However, physical examination is neither very sensitive nor specific in evaluating JIA disease activity compared with MRI. Subclinical synovitis was present in >35 % of presumed clinically inactive patients. (orig.)

A comparison of region-based and pixel-based CEUS kinetics parameters in the assessment of arthritis

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Grisan, E.; Raffeiner, B.; Coran, A.; Rizzo, G.; Ciprian, L.; Stramare, R.

2014-03-01

Inflammatory rheumatic diseases are leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity and increased mortality. The gold-standard for diagnosing and differentiating arthritis is based on patient conditions and radiographic findings, as joint erosions or decalcification. However, early signs of arthritis are joint effusion, hypervascularization and synovial hypertrophy. In particular, vascularization has been shown to correlate with arthritis' destructive behavior, more than clinical assessment. Contrast Enhanced Ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. The evaluation of perfusion pattern rely on subjective semi-quantitative scales, that are able to capture the macroscopic degree of vascularization, but are unable to detect the subtler differences in kinetics perfusion parameters that might lead to a deeper understanding of disease progression and a better management of patients. Quantitative assessment is mostly performed by means of the Qontrast software package, that requires the user to define a region of interest, whose mean intensity curve is fitted with an exponential function. We show that using a more physiologically motivated perfusion curve, and by estimating the kinetics parameters separately pixel per pixel, the quantitative information gathered is able to differentiate more effectively different perfusion patterns. In particular, we will show that a pixel-based analysis is able to provide significant markers differentiating rheumatoid arthritis from simil-rheumatoid psoriatic arthritis, that have non-significant differences in clinical evaluation (DAS28), serological markers, or region-based parameters.

Therapeutic effect of dioscin on collagen-induced arthritis through reduction of Th1/Th2.

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Guo, Yachun; Xing, Enhong; Song, Hongru; Feng, Guiying; Liang, Xiujun; An, Gao; Zhao, Xiaofei; Wang, Mi

2016-10-01

The aim of this study was to detect the therapeutic effect of dioscin on collagen-induced arthritis (CIA). Mice model of CIA was induced by chicken collagen II and arthritis index was assessed. After suspension of dioscin (100mg/kg/d) or triptolide was intragastrically administered, the left paw swelling and body weight of each mouse were measured. Then tissue samples were assayed by histopathological analysis. The levels of Th1 and Th2 were detected by flow cytometry. The expression of p-STAT1, p-STAT4 and p-STAT6 was demonstrated by western blot analysis, and T-bet and GATA-3 expression was detected by RT-PCR. The paw swelling and arthritis index were decreased and body weight was increased in the high dose of dioscin group compared to the model group (PTh1/Th2 in the dioscin group (0.82±0.24) and triptolide group (0.99±0.44) was lower than that in the model group (1.84±0.70, PTh1/Th2 cells, which could reduce the expression of p-STAT4, increase the expression of p-STAT6 and GATA3 in the synovial tissue. Copyright © 2016 Elsevier B.V. All rights reserved.