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Sample records for arthritis synovial fibroblasts

  1. Optimized “In Vitro” Culture Conditions for Human Rheumatoid Arthritis Synovial Fibroblasts

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    Claudia Casnici

    2014-01-01

    Full Text Available The composition of synovial fluid in rheumatoid arthritis (RA is complex and strongly influences the microenvironment of joints and it is an inseparable element of the disease. Currently, “in vitro” studies are performed on RA cells cultured in the presence of either recombinant proinflammatory cytokines-conditioned medium or medium alone. In this study, we evaluated the use of synovial fluid, derived from RA patients, as optimal culture condition to perform “in vitro” studies on RA synovial fibroblasts. We observed that synovial fluid is more effective in inducing cell proliferation with respect to TNF-alpha or culture medium alone. Spontaneous apoptosis in fibroblasts was also decreased in response to synovial fluid. The expression of proinflammatory cytokines in the presence of synovial fluid was significantly elevated with respect to cells cultured with TNF-alpha or medium, and the overall morphology of cells was also modified. In addition, modulation of intracellular calcium dynamics elicited in response to synovial fluid or TNF-alpha exposure is different and suggests a role for the purinergic signalling in the modulation of the effects. These results emphasize the importance of using RA synovial fluid in “in vitro” studies involving RA cells, in order to reproduce faithfully the physiopathological environmental characteristic of RA joints.

  2. The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis.

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    Qin, Suping; Sun, Dexu; Li, Hui; Li, Xiangyang; Pan, Wei; Yan, Chao; Tang, Renxian; Liu, Xiaomei

    2016-04-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment.

  3. Discoidin domain receptor 2 is associated with the increased expression of matrix metalloproteinase-13 in synovial fibroblasts of rheumatoid arthritis.

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    Su, Jin; Yu, Jiangtian; Ren, Tingting; Zhang, Wei; Zhang, Yuanqiang; Liu, Xinping; Sun, Tiezheng; Lu, Houshan; Miyazawa, Keiji; Yao, Libo

    2009-10-01

    Regulation of matrix metalloproteinase-13 (MMP-13) by collagen matrix in the synovial fibroblasts of rheumatoid arthritis (RA) is critical event in the progressive joint destruction. Our previous study indicated that a collagen receptor, discoidin receptor 2 (DDR2), was highly expressed in the synovial fibroblasts of RA. However, the functional role of DDR2 in the regulation of MMP-13 production in synovial fibroblasts has not been elucidated. In this study, we initially demonstrated that the DDR2 and MMP-13 proteins are both highly expressed in the synovial lining layer of RA. MMP-13 mRNA and protein in synovial fibroblasts of RA were preferentially induced by collagen type II compared with MMP-1. Furthermore, stable overexpression of wild type DDR2 in murine synoviocytes dramatically augments the production of MMP-13. The activation of DDR2 also mediates the up-regulation of MMP-13 promoter activity in 293T cells. Inhibitor specific for extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) cascade was shown to decrease MMP-13 level induced by collagen II in RA synovial fibroblasts and DDR2-induced MMP-13 promoter activity. Runx2 and activator protein-1 (AP-1) binding sites in MMP-13 promoter region are required for DDR2-induced transcription. The data in this study suggest that DDR2-mediated MMP-13 induction by collagen matrix in synovial fibroblasts of RA contributed to articular cartilage destruction.

  4. Shikonin Inhibits Inflammatory Response in Rheumatoid Arthritis Synovial Fibroblasts via lncRNA-NR024118

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    Ke-ya Yang

    2015-01-01

    Full Text Available Background. Shikonin is a major chemical component of zicao that possesses anti-inflammatory properties and the ability to mediate cellular and humoral immunity, especially in rheumatoid arthritis (RA. We investigated the impact of shikonin on inflammatory response in RA synovial fibroblasts using the CAIA model. Methods. Severe polyarticular arthritis was induced in Balb/c female mice. Expressions of lncRNA-NR024118, SOCS3, proinflammatory cytokines, and MMPs were evaluated using RT-RCR. Histone acetylation and SOCS3 protein expression were assessed by ChIP assay and western blot, respectively. Results. Mice treated with shikonin showed an abrogation of soft tissue and bone lesions. Shikonin remarkably enhanced the expression of NR024118 and SOCS3 and suppressed the secretion and expression of IL-6, IL-8, and MMPs. Proliferation of cultured RA synovial fibroblasts in the presence of IL-1β was also significantly inhibited by shikonin. Moreover, shikonin dose-dependently increased acetylation of histone H3 at the promoter of NR024118. Finally, NR024118 overexpression and interference significantly changed SOCS3 expression and NR024118 interference could reverse regulation of shikonin on SOCS3, proinflammatory cytokines, and MMPs expression level in MH7A cells. Conclusion. Our results reveal that, in the CAIA mouse model of RA, shikonin has disease modifying activity that is attributable to the inhibition of inflammatory response via lncRNA-NR024118.

  5. Cytoskeletal rearrangements in synovial fibroblasts as a novel pathophysiological determinant of modeled rheumatoid arthritis.

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    Vassilis Aidinis

    2005-10-01

    Full Text Available Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well-recognized tumour necrosis factor-driven animal model of this disease and performed high-throughput expression profiling with subtractive cDNA libraries and oligonucleotide microarray hybridizations, coupled with independent statistical analysis. This twin approach was validated by a number of different methods in other animal models of arthritis as well as in human patient samples, thus creating a unique list of disease modifiers of potential therapeutic value. Importantly, and through the integration of genetic linkage analysis and Gene Ontology-assisted functional discovery, we identified the gelsolin-driven synovial fibroblast cytoskeletal rearrangements as a novel pathophysiological determinant of the disease.

  6. CULTURES OF FIBROBLAST-LIKE SYNOVIAL CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS: PROPERTIES AND OPPORTUNITIES

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    M. A. Schneider

    2016-01-01

    Full Text Available The present review contains data from literature concerning the in vivo structure of synovial membranes in healthy people and patients with rheumatoid arthritis (RA. The properties of in vitro cultured fibroblast-like synovial cells (FLS from RA patients are considered, including FLS morphology, phenotype and function. A standard protocol of in vitro FLS culturing is described. Notably, the FLS are characterized by autonomic functioning, ability for invasive growth/migration, e.g., into non-affected joints. These FLS properties may a reason of multiple joint involvement typical to RA. Special attention is drawn to characterization of stable phenotypic profile of FLS which results from certain epigenetic disturbances, i.e., changes of the DNA methylation, histone acetylation, and micro-RNA effects.The FLS from RA patients are characterized with stable and extensive hypomethylation of genes which occurs in vivo and persists after repeated culture passages. Some promoters of genes involved into RA pathogenesis (for example, CXCL12, IL-6 are hypomethylated. By contrary, some other gene promoters (e.g., the death receptor 3 gene are shown to be hypermethylated. An increased histone acetylation of genes encoding proinflammatory mediators (such as MMP1 may be an important mechanism of persistent inflammation in RA. Changes in histone acetylation in FLS are related to high levels of ubiquitin-like SUMO-1 protein and concurrent decrease in specific protease SENP1activity. A role of histone acetylation in RA pathogenesis is supported by efficacy of a histone deacetylase inhibitor (Trichostatin A in collagen-induced murine arthritis. Local concentrations of micro RNA-155, micro-RNA-146а, and micro-RNA-203 are permanently increased in FLS cultures, synovial tissues, and PBMC of the RA patients. Expression of micro RNA-124а is decreased in FLS from RA, as compared with OA FLS.One may conclude that the fibroblast-like synovial cells are key cellular

  7. Lunasin Inhibits Cell Proliferation via Apoptosis and Reduces the Production of Proinflammatory Cytokines in Cultured Rheumatoid Arthritis Synovial Fibroblasts

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    Shaohui Jia

    2015-01-01

    Full Text Available Lunasin, a peptide with 43 amino acid residues and initially isolated and identified in soybean cotyledon, has gained extensive attention due to its anti-inflammatory and anticancer properties. However, its treatment efficacy on rheumatoid arthritis (RA and corresponding mechanisms have not been reported. Herein, the synovial fibroblasts harvested and isolated from patients with RA were treated with lunasin at various concentrations to examine the proliferation, apoptosis status, and corresponding cell cycle of cultured RA synovial fibroblasts. Meanwhile, the underlying mechanisms of lunasin for RA treatment are explored through Western blot, real-time PCR, ELISA, and luciferase reporter assays. Lunasin significantly inhibited the proliferation and induced the apoptosis of cultured RA synovial fibroblasts. In addition, lunasin reduced the production of interleukin-6 (IL-6, IL-8, and matrix metalloproteinase-3 (MMP-3 and suppressed the activation of NF-κB in cultured RA synovial fibroblasts but did not reveal obvious modulation on the secretion and gene expression of MMP-1. Therefore, lunasin will have promising potential as a novel nutritional supplement or drug candidate for RA due to its potency of suppressing synovial cell proliferation and decreasing the production of proinflammatory cytokines and MMPs in synovial cells.

  8. Epigallocatechin-3-gallate suppresses TNF-alpha -induced production of MMP-1 and -3 in rheumatoid arthritis synovial fibroblasts.

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    Yun, Hee-Jin; Yoo, Wan-Hee; Han, Myung-Kwan; Lee, Young-Rae; Kim, Jong-Suk; Lee, Sang-Il

    2008-11-01

    Rheumatoid arthritis (RA) synovial fibroblasts produce matrix metaloproteinases (MMPs), which destroy cartilage and bone in RA joint. Tumor necrosis factor-alpha (TNF-alpha) is one of the most important mediator leading to MMP production in RA synovial fibroblasts. Here we show that epigallocatechin-3-Gallate (EGCG) suppresses TNF-alpha-induced production of MMP-1 and MMP-3 in RA synovial fibroblasts, which was accompanied by inhibition of mitogen activated protein kinase (MAPK) and activator protein-1 (AP-1) pathways. EGCG treatment resulted in dose-dependent inhibition of TNF-alpha-induced production of MMP-1 and MMP-3 at the protein and mRNA levels in RA synovial fibroblast. EGCG treatment also inhibited TNF-alpha-induced phosphorylation of MAPKs, such as ERK1/2, p38, JNK. Electrophoretic mobility shift assay revealed that EGCG inhibits binding of AP-1 proteins to its response elements in synovial fibroblast treated. Thus, EGCG may play a role in regulating inflammation and bone destruction in RA patients.

  9. Apoptosis is not the major death mechanism induced by celecoxib on rheumatoid arthritis synovial fibroblasts.

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    Audo, Rachel; Deschamps, Véronique; Hahne, Michael; Combe, Bernard; Morel, Jacques

    2007-01-01

    Synovial hyperplasia in rheumatoid arthritis (RA) has been associated with apoptosis deficiency of RA fibroblast-like synoviocytes (FLSs). Celecoxib is a non-steroidal anti-inflammatory drug that has been demonstrated to induce apoptosis in some cellular systems. We have therefore examined the dose- and time-dependent effects of celecoxib on RA FLS viability. Treatment of RA FLSs with celecoxib for 24 hours reduced their viability in a dose-dependent manner. Analysis of celecoxib-treated RA FLSs for their content of apoptotic and necrotic cells by Annexin V staining and TO-PRO-3 uptake displayed only few apoptotic cells. Caspase 3, a key mediator of apoptosis, was not activated in celecoxib-treated RA FLSs, and the presence of specific caspase 3 or pan-caspase inhibitors did not affect celecoxib-induced cell death. Moreover, we could not detect other signs of apoptosis, such as cleavage of poly(ADP-ribose) polymerase, caspase 8 or 9, or DNA fragmentation. We therefore conclude that apoptosis is not the major death pathway in celecoxib-treated RA FLSs.

  10. 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.

  11. 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

    2015-01-01

    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. PMID:26134265

  12. 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

    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 (1-5μM) 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 (pinhibited TNF-α-induced phospho-p38 and phospho-JNK expression, but had no inhibitory effect on NF-κB pathway, in RA-FLS (pTNF-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 (pTNF-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.

  13. 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

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

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    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

    2016-01-01

    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.

  15. Annexin A2 is a target of autoimmune T and B cell responses associated with synovial fibroblast proliferation in patients with antibiotic-refractory Lyme arthritis.

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    Pianta, Annalisa; Drouin, Elise E; Crowley, Jameson T; Arvikar, Sheila; Strle, Klemen; Costello, Catherine E; Steere, Allen C

    2015-10-01

    In this study, autoantibody responses to annexin A2 were found in 11-15% of 278 patients with Lyme disease, including in those with erythema migrans (EM), an early sign of the illness, and in those with antibiotic-responsive or antibiotic-refractory Lyme arthritis (LA), a late disease manifestation. In contrast, robust T cell reactivity to annexin A2 peptides was found only in patients with responsive or refractory LA. In LA patients, annexin A2 protein levels, which were higher in the refractory group, correlated with annexin A2 antibody levels in sera and synovial fluid. In addition, in patients with antibiotic-refractory LA who had anti-annexin A2 antibodies, synovial tissue had intense staining for annexin A2 protein, greater synovial fibroblast proliferation and more tissue fibrosis. Thus, a subset of LA patients had T and B cell responses to annexin A2, and in the refractory group, annexin A2 autoantibodies were associated with specific pathologic findings.

  16. Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs.

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    Yoon, Ha-Yong; Lee, Eun-Gyeong; Lee, Hyun; Cho, In Jin; Choi, Yun Jung; Sung, Myung-Soon; Yoo, Han-Gyul; Yoo, Wan-Hee

    2013-10-01

    Inflammatory cytokines, matrix metalloproteinases (MMPs) and cyclooxygenase (COX)-2 released from rheumatoid arthritis synovial fibroblasts (RASFs) are involved in the destruction of both articular bone and cartilage. Kaempferol has been reported to act as an antioxidant and anti-inflammatory agent by inhibiting nitric oxide synthase and COX enzymes. The aim of the present study was to determine the effects of kaempferol on the interleukin-1β (IL-1β)-induced proliferation of RASFs and the production of MMPs, COX and prostaglandin E2 (PGE2) by RASFs. The proliferation of the RASFs stimulated with IL-1β and treated with/without kaempferol was evaluated by CCK-8 assay. The expression of MMPs, TIMP metallopeptidase inhibitor-1 (TIMP-1), COXs, PGE2 and that of intracellular MAPK signaling molecules, including p-ERK, p-p38, p-JNK and nuclear factor-κB (NF-κB) was examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA under the conditions described above. Kaempferol inhibited the proliferation of both unstimulated and IL-1β‑stimulated RASFs, as well as the mRNA and protein expression of MMP-1, MMP-3, COX-2 and PGE2 induced by IL-1β. Kaempferol also inhibited the phosphorylation of ERK-1/2, p38 and JNK, as well as the activation of NF-κB induced by IL-1β. These results indicate that kaempferol inhibits synovial fibroblast proliferation, as well as the production of and MMPs, COX‑2 and PGE2, which is involved in articular inflammation and destruction in rheumatoid arthritis (RA). Our data suggest that kaempferol may be a novel therapeutic agent for the treatment of RA.

  17. Hyaluronic acid production by irradiated human synovial fibroblasts

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    Yaron, M.; Yaron, I.; Levita, M.; Herzberg, M.

    1977-03-01

    Radioactive particles as well as x irradiation from an external source has been used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In order to clarify effects of ionizing irradiation on synovial cells, radioactive gold (/sup 198/Au) and yttrium (/sup 90/Y) were added to fibroblast cultures derived from human synovial membranes. Other cultures were irradiated by a Picker x-ray machine. Fibroblast growth and hyaluronic acid production were measured. Radioactive gold and yttrium particles induced a significant increase of hyaluronic acid synthesis rate (pg/cell/day) and inhibited fibroblast growth. Fibroblasts continued to overproduce hyaluronic acid and to show growth inhibition 3 weeks after irradiation with radioactive gold. Hydrocortisone inhibited hyaluronic acid overproduction induced by radioactive gold. Overproduction of hyaluronic acid induced by the x-ray machine was inhibited by hydrocortisone, actinomycin-D, and cycloheximide. Fibroblasts derived from normal and rheumatoid patients responded similarly to ionizing irradiation.

  18. Largazole, a class I histone deacetylase inhibitor, enhances TNF-α-induced ICAM-1 and VCAM-1 expression in rheumatoid arthritis synovial fibroblasts

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    Ahmed, Salahuddin, E-mail: Salah.Ahmed@utoledo.edu [Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States); Riegsecker, Sharayah; Beamer, Maria; Rahman, Ayesha; Bellini, Joseph V. [Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States); Bhansali, Pravin; Tillekeratne, L.M. Viranga [Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States)

    2013-07-15

    In the present study, we evaluated the effect of largazole (LAR), a marine-derived class I HDAC inhibitor, on tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) activity. LAR (1–5 μM) had no adverse effect on the viability of RA synovial fibroblasts. Among the different class I HDACs screened, LAR (0.5–5 μM) inhibited the constitutive expression of HDAC1 (0–30%). Surprisingly, LAR increased class II HDAC [HDAC6] by ∼ 220% with a concomitant decrease in HDAC5 [30–58%] expression in RA synovial fibroblasts. SAHA (5 μM), a pan-HDAC inhibitor, also induced HDAC6 expression in RA synovial fibroblasts. Pretreatment of RA synovial fibroblasts with LAR further enhanced TNF-α-induced ICAM-1 and VCAM-1 expression. However, LAR inhibited TNF-α-induced MMP-2 activity in RA synovial fibroblasts by 35% when compared to the TNF-α-treated group. Further, the addition of HDAC6 specific inhibitor Tubastatin A with LAR suppressed TNF-α + LAR-induced ICAM-1 and VCAM-1 expression and completely blocked MMP-2 activity, suggesting a role of HDAC6 in LAR-induced ICAM-1 and VCAM-1 expression. LAR also enhanced TNF-α-induced phospho-p38 and phospho-AKT expression, but inhibited the expression of phospho-JNK and nuclear translocation of NF-κBp65 in RA synovial fibroblasts. These results suggest that LAR activates p38 and Akt pathways and influences class II HDACs, in particular HDAC6, to enhance some of the detrimental effects of TNF-α in RA synovial fibroblasts. Understanding the exact role of different HDAC isoenzymes in RA pathogenesis is extremely important in order to develop highly effective HDAC inhibitors for the treatment of RA. - Highlights: • Largazole enhances TNF-α-induced ICAM-1 and VCAM-1. • Largazole upregulates class II HDAC (HDAC6) in RA synovial fibroblasts. • Largazole also induces the expression of phospho-p38

  19. Role of synovial fibroblast in the pathogenesis of rheumatoid arthritis%滑膜成纤维细胞在类风湿性关节炎发病中的作用

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    贺琤雯; 沈茜

    2010-01-01

    类风湿性关节炎是复杂的多系统疾病,近年来,越来越多的证据表明,滑膜成纤维细胞在.类风湿性关节炎中过度增殖,介导炎症反应,造成关节结构破坏.滑膜成纤维细胞在类风湿性关节炎发病过程中具有重要的作用.%Rheumatoid arthritis(RA)is a complex multisystem disease.In recent years,growing evidence demonstrated that rheumatoid arthritis synovial fibroblasts(BASF)play an important role in the pathogenesis of rheumatoid arthritis.In this article,we review the evidence that implicates the RASF as a central player in the propagation of rheumatoid arthritis.

  20. Genetherapy with adenovirus expressing ATF-BPTI hybrid protein inhibits proteolysis by rheumatoid synovial fibroblasts

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    Laan, W.H. van der; Grimbergen, J.M.; Verheijen, J.H.; Pha, Q.

    1998-01-01

    In rheumatoid arthritis (RA), irreversible joint damage is the result of degradation of articular structures such as cartilage, bone and tendons. The plasminogen activator (PA) system has been shown to be involved in the proteolytic degradation of cartilage matrix by rheumatoid synovial fibroblasts

  1. Expression of molecules involved in B lymphocyte survival and differentiation by synovial fibroblasts.

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    Edwards, J C; Leigh, R D; Cambridge, G

    1997-06-01

    The synovitis of rheumatoid arthritis (RA) is one of few pathological lesions in which B lymphocyte accumulation progresses to the extent of germinal centre formation. The present study was designed to assess the ability of synovial fibroblasts to express molecules implicated in B lymphocyte survival and differentiation, both in vivo, and in response to cytokines in vitro. Normal and diseased synovia were examined by indirect immunofluorescence. In all tissues synovial intimal fibroblasts showed co-expression of vascular cell adhesion molecule-1 (VCAM-1) and complement decay-accelerating factor (DAF) comparable to that of follicular dendritic cells (FDC), but not complement receptor 2 (CR2). In rheumatoid synovia, subintimal cells showed variable expression of VCAM-1 and DAF, with bright co-expression of VCAM-1, DAF and CR2 in lymphoid follicle centres. B lymphocytes, some of which were proliferating cell nuclear antigen-positive, were present in contact with subintimal cells expressing VCAM-1 with or without DAF or CR2. B lymphocytes were rarely present in the intimal layer, and, where present, showed fragmentation. In vitro, synovial fibroblasts exposed to tumour necrosis factor-alpha (TNF-alpha) in combination with interferon-gamma (IFN-gamma) showed enhanced expression of VCAM-1, in comparison with fibroblasts from skin and lung and, unlike skin and lung fibroblasts, also expressed DAF and CR2. These findings support the hypothesis that synovial targeting in RA involves an enhanced ability of synovial fibroblasts to support B lymphocyte survival. This appears to be dependent, not on the constitutive expression of VCAM-1 and DAF on intimal cells, but on the increased ability of subintimal cells to respond to proinflammatory cytokines, perhaps critically in the expression of VCAM-1.

  2. Oral bacterial DNAs in synovial fluids of arthritis patients

    OpenAIRE

    Moen, Ketil; Johan G. Brun; Eribe, Emenike R.K.; Olsen, Ingar; Jonsson, Roland

    2011-01-01

    Arthritis may be triggered by microbial constituents, more specifically, bacterial cell wall fragments, or bacterial DNA. The aim of this study was to analyze the amount of oral bacterial DNA in synovial fluids (SF) of arthritis patients. SF from 15 rheumatoid arthritis (RA) patients, 15 arthritides (non-RA) patients and 9 osteoarthritis (control) patients were extracted for oral bacterial DNA. DNA was used in a checkerboard DNA/DNA hybridization set-up, in order to identify 40 different spec...

  3. Up-regulation of prostaglandin E receptor EP2 and EP4 subtypes in rat synovial tissues with adjuvant arthritis.

    Science.gov (United States)

    Kurihara, Y; Endo, H; Akahoshi, T; Kondo, H

    2001-02-01

    To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis.

  4. Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis

    OpenAIRE

    2012-01-01

    Introduction Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination. Methods Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patie...

  5. Involvement of transient receptor potential melastatin-8 (TRPM8) in menthol-induced calcium entry, reactive oxygen species production and cell death in rheumatoid arthritis rat synovial fibroblasts.

    Science.gov (United States)

    Zhu, Shuyan; Wang, Yuxiang; Pan, Leiting; Yang, Shuang; Sun, Yonglin; Wang, Xinyu; Hu, Fen

    2014-02-15

    Rheumatoid arthritis is most prominently characterized by synoviocyte hyperplasia which therefore serves as an important target for clinical therapy. In the present study, it was observed that menthol, the specific agonist of transient receptor potential melastatin subtype 8 (TRPM8), could induce sustained increases of cytosolic calcium concentration ([Ca(2+)]c) in synoviocytes isolated from collagen-induced arthritis rats in dose-dependent manner, which was evidently blocked by applying an extracellular Ca(2+)-free buffer. Menthol-induced [Ca(2+)]c increase was also significantly inhibited by potent TRPM8 antagonist capsazepine (CZP), indicating that this [Ca(2+)]c elevation was mostly attributed to TRPM8-mediated Ca(2+) entry. Besides, RT-PCR indeed demonstrated presence of TRPM8 in the synoviocytes. Meanwhile, it was found that menthol evoked production of intracellular reactive oxygen species, which could be abolished by Ca(2+) free solutions or CZP. Further experiments showed that menthol reduced the cell numbers and survival of synoviocytes. This reduction was associated with apoptosis as suggested by mitochondrial membrane depolarization, nuclear condensation and a caspase 3/7 apoptotic assay. Menthol-induced death and apoptosis of synoviocytes both were obviously inhibited by CZP, intracellular calcium chelator BAPTA-AM, and reactive oxygen species inhibitor diphenylene iodonium, respectively. Taken together, our data indicated that menthol resulted in synoviocyte death associated with apoptosis via calcium entry and reactive oxygen species production depending on TRPM8 activation.

  6. Staphylococcal Superantigens in Synovial Fluid of 62 Patients With Arthritis

    Directory of Open Access Journals (Sweden)

    A Tabatabaei

    2012-04-01

    Full Text Available Background: Determining the etiologic causes of septic arthritis is of the most importance. Goal of this study was to investigate presence of staphylococcal enterotoxins A, B, C and Toxic Shock Staphylococcal toxin-1 in the synovial fluid of patients with arthritis. Methods: This cross-sectional study was performed in the Pediatric and Orthopedic Wards of Hazrat Rasoul Hospital in Tehran, Iran during 2008- 2010. Gram stains, conventional cultures, direct detection of soluble bacterial antigens were used to detect H. influenza, S. pneumonia, group B streptococci, and N. meningitidis while Latex particle agglutination test was used for staphylococcal supper antigens (by enzyme immunoassays upon synovial fluid tapping of 62 individuals (5 mo to 16 yrs, mean=113.8 yrs. P<0.05 was considered statistically significant. Results: Positive SF cultures (n=11: 5 positive cases of S. aureus; 5 S. pneumonia; 1 H. influenza, and 1 Klebsiella. Positive gram stains: 10%; and positive LPA: 4%. Staphylococcal arthritis was diagnosed in 7 (39% cases upon positive culture or positive gram stain. The most common type was TSST-1 (47% and the least common was enterotoxin B (18%. Isolation of S. aureus (positive culture was correlated to presence of enterotoxin A in synovial fluid but not to enterotoxins B, C or TSST-1. Conclusion: Staph. aureus had a prominent role in arthritis. 47% of cases with negative culture for S. aureus had at least one type of staphylococcal super antigens in the synovial fluid. Searching for antigens of usual organisms or staphylococcal supper antigens could be helpful for diagnosis and subsequent treatment.

  7. Ceramide, a mediator of interleukin 1, tumour necrosis factor α, as well as Fas receptor signalling, induces apoptosis of rheumatoid arthritis synovial cells

    OpenAIRE

    Mizushima, N; Kohsaka, H.; Miyasaka, N

    1998-01-01

    OBJECTIVES—To examine the effects of ceramide, which is a lipid second messenger of cell surface receptors, including tumour necrosis factor α (TNFα), interleukin 1 (IL1), and Fas receptors, on rheumatoid arthritis (RA) synovial cells.
METHODS—Synovial cells from RA patients and normal skin fibroblasts were cultured with cell permeable ceramide (C2-ceramide). Apoptosis was assessed by microscopic observation of morphological changes, nuclear staining, and DNA electrophoresis. DNA synthesis wa...

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

    DEFF Research Database (Denmark)

    Kyvsgaard, Nini; Herlin, Troels

    2015-01-01

    BACKGROUND: Large synovial cysts are rarely seen in juvenile idiopathic arthritis. When they do appear, they usually appear in the popliteal space (Baker’s cyst). Less commonly, they occur in the antecubital area or as bicipital synovial cysts. Bicipital synovial cysts present as a sudden...

  9. Effects of Thapsigargin on the Proliferation and Survival of Human Rheumatoid Arthritis Synovial Cells

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2014-01-01

    Full Text Available A series of experiments have been carried out to investigate the effects of different concentrations of thapsigargin (0, 0.001, 0.1, and 1 μM on the proliferation and survival of human rheumatoid arthritis synovial cells (MH7A. The results showed that thapsigargin can block the cell proliferation in human rheumatoid arthritis synovial cells in a time- and dose-dependent manner. Results of Hoechst staining suggested that thapsigargin may induce cell apoptosis in MH7A cells in a time- and dose-dependent manner, and the percentages of cell death reached 44.6% at thapsigargin concentration of 1 μM treated for 4 days compared to the control. The protein and mRNA levels of cyclin D1 decreased gradually with the increasing of thapsigargin concentration and treatment times. Moreover, the protein levels of mTORC1 downstream indicators pS6K and p4EBP-1 were reduced by thapsigargin treatment at different concentrations and times, which should be responsible for the reduced cyclin D1 expressions. Our results revealed that thapsigargin may effectively impair the cell proliferation and survival of MH7A cells. The present findings will help to understand the molecular mechanism of fibroblast-like synoviocytes proliferations and suggest that thapsigargin is of potential for the clinical treatment of rheumatoid arthritis.

  10. TRPM3 channel stimulated by pregnenolone sulphate in synovial fibroblasts and negatively coupled to hyaluronan

    Directory of Open Access Journals (Sweden)

    English Anne A

    2010-06-01

    Full Text Available Abstract Background Calcium-permeable channels are known to have roles in many mammalian cell types but the expression and contribution of such ion channels in synovial cells is mostly unknown. The objective of this study was to investigate the potential relevance of Transient Receptor Potential Melastatin 3 (TRPM3 channel to fibroblast-like synoviocytes (FLSs of patients with rheumatoid arthritis. Methods The study used RT-PCR and immunofluorescence to detect mRNA and protein. Intracellular calcium measurement detected channel activity in a FLS cell-line and primary cultures of FLSs from patients with rheumatoid arthritis. Enzyme-linked immunosorbent assays measured hyaluronan. Results Endogenous expression of TRPM3 was detected. Previously reported stimulators of TRPM3 sphingosine and pregnenolone sulphate evoked sustained elevation of intracellular calcium in FLSs. The FLS cell-line showed an initial transient response to sphingosine which may be explained by TRPV4 channels but was not observed in FLSs from patients. Blocking antibody targeted to TRPM3 inhibited sustained sphingosine and pregnenolone sulphate responses. Secretion of hyaluronan, which contributes adversely in rheumatoid arthritis, was suppressed by pregnenolone sulphate in FLSs from patients and the effect was blocked by anti-TRPM3 antibody. Conclusions The data suggest that FLSs of patients with rheumatoid arthritis express TRPM3-containing ion channels that couple negatively to hyaluronan secretion and can be stimulated by pharmacological concentrations of pregnenolone sulphate.

  11. 11β-hydroxysteroid dehydrogenase enzymes modulate effects of glucocorticoids in rheumatoid arthritis synovial cells.

    Science.gov (United States)

    Schmidt, Martin; Straub, Rainer H

    2015-01-01

    The tissue availability of active glucocorticoids (cortisol in humans) depends on their rate of synthesis from cholesterol, downstream metabolism, excretion and interconversion. The latter is mediated by the 11β-hydroxysteroid dehydrogenases (11βHSDs). In this review, we summarize the features of the two isoenzymes, 11βHSD1 and 11βHSD2, and current available experimental data related to 11βHSDs, which are relevant in the context of synovial cells in rheumatoid arthritis (RA). We conclude that due to complex feedback mechanisms inherent to the hypothalamic-pituitary-adrenal axis, currently available transgenic animal models cannot display the full potential otherwise inherent to the techniques. Studies with tissue explants, mixed synovial cell preparations, cell lines derived from synovial cells, and related primary cells or established cell lines indicate that there are relatively clear differences between the two isoenzymes. 11βHSD1 is expressed primarily in fibroblasts and osteoblasts, and may be responsible for fibroblast survival and aid in the resolution of inflammation, but it is also involved in bone damage. 11βHSD2 is expressed primarily in macrophages and lymphocytes, and may be responsible for their survival, suggesting that it is critical in chronic inflammation. The situation in synovial tissue would allow 11βHSD2-expressing cells to tap the energy resources of 11βHSD1-expressing cells. The overall properties of this local glucocorticoid interconversion system might limit therapeutic use of glucocorticoids in RA. © 2014 S. Karger AG, Basel.

  12. Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint

    Directory of Open Access Journals (Sweden)

    Toshio Hattori

    2015-01-01

    Full Text Available Synovial fibroblasts contribute to the inflammatory temporomandibular joint under pathogenic stimuli. Synovial fibroblasts and T cells participate in the perpetuation of joint inflammation in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. IL-17 is an inflammatory cytokine produced primarily by Th17 cells which plays critical role in the pathogenesis of numerous autoimmune and inflammatory diseases. Here, we investigated the roles of IL-17A in temporomandibular joint disorders (TMD using genome-wide analysis of synovial fibroblasts isolated from patients with TMD. IL-17 receptors were expressed in synovial fibroblasts as assessed using real-time PCR. Microarray analysis indicated that IL-17A treatment of synovial fibroblasts upregulated the expression of IL-6 and chemokines. Real-time PCR analysis showed that the gene expression of IL-6, CXCL1, IL-8, and CCL20 was significantly higher in IL-17A-treated synovial fibroblasts compared to nontreated controls. IL-6 protein production was increased by IL-17A in a time- and a dose-dependent manner. Additionally, IL-17A simulated IL-6 protein production in synovial fibroblasts samples isolated from three patients. Furthermore, signal inhibitor experiments indicated that IL-17-mediated induction of IL-6 was transduced via activation of NFκB and phosphatidylinositol 3-kinase/Akt. These results suggest that IL-17A is associated with the inflammatory progression of TMD.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. A Comparative Metabolomic Evaluation of Behcet's Disease with Arthritis and Seronegative Arthritis Using Synovial Fluid.

    Science.gov (United States)

    Ahn, Joong Kyong; Kim, Sooah; Kim, Jungyeon; Hwang, Jiwon; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Behcet's disease (BD) with arthritis is often confused with seronegative arthritis (SNA) because of shared clinical symptoms and the lack of definitive biomarkers for BD. To investigate possible metabolic patterns and potential biomarkers of BD with arthritis, metabolomic profiling of synovial fluid (SF) from 6 patients with BD with arthritis and 18 patients with SNA was performed using gas chromatography/time-of-flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. A total of 123 metabolites were identified from samples. Orthogonal partial least square-discriminant analysis showed clear discrimination between BD with arthritis and SNA. A set of 11 metabolites were identified as potential biomarkers for BD using variable importance for projection values and the Wilcoxon-Mann-Whitney test. Compared with SNA, BD with arthritis exhibited relatively high levels of glutamate, valine, citramalate, leucine, methionine sulfoxide, glycerate, phosphate, lysine, isoleucine, urea, and citrulline. There were two markers identified, elevated methionine sulfoxide and citrulline, that were associated with increased oxidative stress, providing a potential link to BD-associated neutrophil hyperactivity. Glutamate, citramalate, and valine were selected and validated as putative biomarkers for BD with arthritis (sensitivity, 100%; specificity, 61.1%). This is the first report to present potential biomarkers from SF for discriminating BD with arthritis from SNA. The metabolomics of SF may be helpful in searching for potential biomarkers and elucidating the clinicopathogenesis of BD with arthritis.

  15. Staphylococcal Enterotoxin A Detection from Rheumatoid Arthritis Patients’ Blood and Synovial Fluid

    OpenAIRE

    2016-01-01

    Introduction Direct detection of microbial super antigens in synovial fluid of patients with rheumatoid arthritis may be able to guide to the design of cost-effective therapies. The purpose of this study was to assess the existence of Staphylococcal enterotoxin A (superantigen A) in the synovial fluid of patients with RA by the PCR and ELISA methods. Methods This experimental study was conducted on the synovial fluid of 103 RA patients from Baqiyatallah University of Medical Sciences’ Rheumat...

  16. Distinct synovial immunopathologic characteristics of juvenile-onset spondylarthritis and other forms of juvenile idiopathic arthritis

    NARCIS (Netherlands)

    E. Kruithof; V. van den Bossche; L. de Rycke; B. Vandooren; R. Joos; J.D. Canete; P.P. Tak; A.M.H. Boots; E.M. Veys; D. Baeten

    2006-01-01

    Objective. To characterize the synovial immunopathologic features of juvenile-onset spondylarthritis (SpA) in relation to adult SpA and other forms of juvenile idiopathic arthritis (JIA). Methods. Synovial biopsy samples were obtained from 10 patients with juvenile-onset SpA, 23 with adult SpA, 19 w

  17. Plasma and synovial fluid meclofenamic acid concentrations in patients with rheumatoid arthritis of the knee.

    Science.gov (United States)

    Koup, J R; Thomas, D; Tucker, E; Black, A; Ruderman, M; Dixon, J A; Kinkel, A

    1988-01-01

    We have measured plasma and synovial fluid concentrations of meclofenamic acid at 2, 4, 8, and 12 h during steady-state administration (100 mg three times daily for 4-7 days). Paired plasma and synovial samples were obtained pre-treatment and at one of the above times in twelve patients with a diagnosis of rheumatoid arthritis. In addition, the extent of protein binding of meclofenamic acid was assessed in vitro in the pre-treatment plasma and synovial fluid specimens. Peak total concentrations of 1.73 and 0.86 micrograms.ml-1 were observed in plasma (at 2 h) and synovial fluid (at 4 h) respectively. The extent of protein binding was 99.7 and 99.6% (not significantly different) in plasma and synovial fluid respectively. The results of this study are compared to those from similar reported studies of other nonsteroidal anti-inflamatory compounds.

  18. Programmed cell death 5 correlates with disease activity and interleukin-17 in serum and synovial fluid of rheumatoid arthritis patients

    Institute of Scientific and Technical Information of China (English)

    WANG Jun-feng; GUAN Zhen-peng; ZHANG Shao-long; PEI Zheng; CHEN Ying-yu; PAN Huan

    2013-01-01

    Background Programmed cell death 5 (PDCD5) is a novel apoptotic regulatory gene that promotes apoptosis in various tumor cells.Studies have shown that PDCD5 accelerates the apoptosis of synoviocytes in vitro,implying a potential role in rheumatoid arthritis (RA) pathogenesis.This study examined the expression of PDCD5 in serum and synovial fluid of RA patients,its effect on the expression of inflammatory cytokine,interleukin-17 (IL-17),and the assessment of disease activity in RA.Methods PDCD5 and IL-17 levels in serum and synovial fluid from 18 patients with RA and 22 patients with osteoarthritis (OA) were detected using enzyme-linked immunosorbent assay (ELISA).Concentrations of serum PDCD5 in 40 healthy people were also detected as controls.As disease activity indices,C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),rheumatoid factor (RF),and X-ray grading scale were also evaluated.Results Serum and synovial fluid PDCD5 levels in RA patients were significantly higher than those in OA and healthy controls.Serum PDCD5 level was inversely correlated to CRP and ESR,and was significantly higher in the RF negative group than in the positive group.PDCD5 level was also negatively correlated with IL-17 levels both in serum and synovial fluid of RA patients.However,differences in synovial fluid PDCD5 level from RA patients at different Larsen stages were not detectable.Conclusions PDCD5 affects RA pathogenesis.Insufficient apoptosis of fibroblast-like synoviocytes and inflammatory cells in RA could increase the expression of PDCD5 protein.As PDCD5 levels correlated negatively with disease activity indices and IL-17 level,PDCD5 could become a target in the diagnosis and treatment of RA.

  19. Lyme arthritis. Spirochetes found in synovial microangiopathic lesions.

    Science.gov (United States)

    Johnston, Y. E.; Duray, P. H.; Steere, A. C.; Kashgarian, M.; Buza, J.; Malawista, S. E.; Askenase, P. W.

    1985-01-01

    In 17 patients with Lyme disease, synovial specimens, obtained by synovectomy or needle biopsy, showed nonspecific villous hypertrophy, synovial cell hyperplasia, prominent microvasculature, lymphoplasmacellular infiltration, and sometimes lymphoid follicles. The larger surgically obtained specimens also showed striking deposition of fibrin in synovial stroma and a form of endarteritis obliterans. In 2 patients, spirochetes were seen in and around blood vessels by the Dieterle silver stain. Compared with 55 cases of other synovial disease, obliterative microvascular lesions were seen only in Lyme synovia, but marked stromal deposition of fibrin seemed nonspecific. These findings imply that the Lyme spirochete may survive for years in affected synovium and may be directly responsible for the microvascular injury. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3966535

  20. MicroRNA-16对类风湿关节炎患者滑膜成纤维细胞增殖、侵袭及细胞因子分泌的影响%Effects of microRNA-16 on proliferation, invasion and cytokine secretion of synovial fibroblasts from rheumatoid arthritis patients

    Institute of Scientific and Technical Information of China (English)

    史栋梁; 史桂荣

    2014-01-01

    目的:研究microRNA-16(miR-16)对类风湿关节炎(rheumatoid arthritis,RA)患者滑膜成纤维细胞( rheumatoid arthritis synovial fibroblasts,RASFs)增殖、侵袭及细胞因子分泌的影响。方法:体外分离培养RASFs,脂质体转染化学合成的miR-16 mimic或miR-16抑制剂,分别采用MTT法、Transwell小室法和流式细胞术检测其对RASFs增殖、侵袭及凋亡的影响;RT-PCR和Western blotting检测miR-16对RASFs 基质金属蛋白酶3/13( matrix metalloproteinase 3/13,MMP3/13)及白细胞介素1β( interleukin 1β,IL-1β)表达的影响。结果:增殖实验结果表明miR-16可显著抑制RASFs的增殖;细胞侵袭结果表明miR-16可显著抑制RASFs的侵袭;流式细胞术检测发现miR-16对RASFs凋亡无显著影响;miR-16可下调MMP3/13及IL-1β的表达水平。结论:miR-16在RA的发生中起着重要作用,它可能通过下调MMP3/13及IL-1β的表达抑制RASFs增殖和侵袭。这为进一步研究miR-16在RA中的作用机制奠定了基础。%AIM:To investigate the effect of microRNA-16 ( miR-16) on the proliferation, invasion and cyto-kine secretion of rheumatoid arthritis ( RA) synovial fibroblasts ( RASFs) from the RA patients.METHODS: miR-16 mimic and miR-16 inhibitor were synthesized, and then Transfected into RASFs isolated from RA patients with lipo-fectamine.MTT assay, Transwell chamber and flow cytometry were used to determine the effect of miR-16 on proliferation, invasion and apoptosis of RASFs.The expression of matrix metalloproteinase 3/13 ( MMP3/13) and interleukin 1β( IL-1β) was measured by RT-PCR and Western blotting.RESULTS: The proliferation and invasion of RASFs were signifi-cantly inhibited by miR-16 mimic.The result of flow cytometry demonstrated that miR-16 had no effect on apoptosis of RASFs.Furthermore, miR-16 down-regulated the expression of MMP3/13 and IL-1β.CONCLUSION:miR-16 plays an important role in the development of RA and may

  1. Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Duby, A.D.; Sinclair, A.K.; Osborne-Lawrence, S.L. (Univ. of Texas Southwestern Medical Center, Dallas (USA)); Zeldes, W.; Kan, Li; Fox, D.A. (Univ. of Michigan, Ann Arbor (USA))

    1989-08-01

    Although substantial evidence suggests that synovial T lymphocytes are critical in the pathogenesis of rheumatoid arthritis (RA), little is known regarding their antigenic specificities, antigen receptor gene rearrangements, and mechanisms of activation. To assess the extend of expansion of specific clones among RA synovial fluid T cells, Southern blot analyses of T-cell receptor (TCR) gene rearrangements were performed on 40 RA synovial fluid T-cell clones, as well as on fresh and polyclonally activated T cells from RA synovial fluid, RA peripheral blood, and normal peripheral blood. Two of the clones had identical TCR rearrangement patterns, but the remainder were unique. The nonclonal RA T-cell samples showed the same pattern of TCR {beta}-chain rearrangement that was observed among normal peripheral blood T cells, indicating no dominant clonal T-cell population in these samples. It was noted that with sufficient exposure of autoradiograms of the Southern blots, discrete TCR gene rearrangements, representing in some cases common D{sub {beta}}J{sub {beta}} (D, diversity; J, joining) rearrangements, were evident in T cells from peripheral blood of normal individuals and patients with RA, as well as T cells from RA synovial fluid. Taken together, the findings indicate that only a minor degree of oligoclonality can be demonstrated among T lymphocytes from RA synovial fluid.

  2. 黑骨藤乙醇提取物影响人类风湿关节炎滑膜成纤维细胞增殖及COX-2、PGE-2表达的研究%Effects of Periploca forrestii ethanol extract(PFE) on proliferation, COX-2 expression,and PG2 expression of Rheumatoid arthritis synovial fibroblasts from patients

    Institute of Scientific and Technical Information of China (English)

    梁江; 马武开; 刘正奇; 安阳; 姚血明; 唐志宇

    2015-01-01

    目的 观察黑骨藤乙醇提取物(Periploca forrestii ethanol extract,PFE)对人类风湿关节炎滑膜成纤维细胞(Rheumatoid arthritis synovial fibroblasts,RASF)的增殖以及环氧化酶-2(cyclooxygenase-2,COX-2)、前列腺素2(prostaglandin E2,PGE2)的表达影响.方法 离体培养第4代的人类风湿关节炎滑膜成纤维细胞,同时设立空白对照组和试验组,两组细胞均先予白介素-1β(interleukin-1β,IL-1β)干预刺激,试验组予不同浓度的PFE(125,250,500μg/ml)干预细胞,24h后,采用MTT法检测细胞抑制率.用RT-RCR法测定COX-2的mRNA表达.免疫蛋白印记(WB法)检测COX-2的表达量,ELISA法检测48h末,细胞培养上清中PGE2的含量,结果 干预48h后,PFE对细胞抑制率呈量-效果正相关性,各剂量组的PFE对PGE2、COX-2mRNA及其蛋白的表达量有明显抑制(P<0.05),结论 PFE能抑制IL-1β诱导的RASF增殖,在mRNA和蛋白两个层面均对RASF高表达的COX-2有明显抑制效果,同时对该细胞分泌的炎症效应分子PGE2也有抑制作用,这可能是黑骨藤治疗类风湿关节炎的潜在机制之一.

  3. 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

    as follows: An acute preimmune phase with inflammatory changes and synovial membrane reactions dominates the first week of the infection. By the second and third week, the peak of the immune phase with masses of plasma cells and lymphocytes is seen. By 7 weeks, there is healing with moderate fibrosis. Mild...... 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...... ongoing reactions or recurrence of arthritis, perhaps related to persistence of mycoplasma antigens, may be seen in later phases and local antibody production may be important in this infection....

  4. Procalcitonin levels in fresh serum and fresh synovial fluid for the differential diagnosis of knee septic arthritis from rheumatoid arthritis, osteoarthritis and gouty arthritis.

    Science.gov (United States)

    Wang, Chenggong; Zhong, DA; Liao, Qiande; Kong, Lingyu; Liu, Ansong; Xiao, Han

    2014-10-01

    Whether the levels of procalcitonin (PCT) in the serum and synovial fluid are effective indicators for distinguishing septic arthritis (SA) from non-infectious arthritis remains controversial. The present study aimed to evaluate whether PCT levels in fresh serum or fresh joint fluid may be used in the differential diagnosis of SA from rheumatoid arthritis (RA), osteoarthritis (OA) and gouty arthritis (GA). From January 2012 to June 2013, 23 patients with knee SA, 21 patients with RA, 40 patients with OA and 11 patients with GA were enrolled in the current study. The levels of PCT were measured within 24 h after specimen collection at room temperature. An enzyme-linked fluorescence assay (ELFA) was used to detect the levels of PCT in the serum and synovial fluid. The correlations between the levels of PCT in the serum and synovial fluid and the arthritic patient groups were determined by the Nemenyi test. Areas under the receiver operating characteristic (ROC) curve were calculated to evaluate the accuracy of the correlations. The levels of PCT in the serum and joint fluid of the patients in the SA group were higher compared with those of the other groups (Parthritis; however, the PCT levels in fresh synovial fluid are more sensitive and accurate indicators than PCT levels in fresh serum.

  5. Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis.

    Directory of Open Access Journals (Sweden)

    Marzia Dolcino

    Full Text Available Psoriatic arthritis (PsA is an inflammatory arthritis whose pathogenesis is poorly understood; it is characterized by bone erosions and new bone formation. The diagnosis of PsA is mainly clinical and diagnostic biomarkers are not yet available. The aim of this work was to clarify some aspects of the disease pathogenesis and to identify specific gene signatures in paired peripheral blood cells (PBC and synovial biopsies of patients with PsA. Moreover, we tried to identify biomarkers that can be used in clinical practice.PBC and synovial biopsies of 10 patients with PsA were used to study gene expression using Affymetrix arrays. The expression values were validated by Q-PCR, FACS analysis and by the detection of soluble mediators.Synovial biopsies of patients showed a modulation of approximately 200 genes when compared to the biopsies of healthy donors. Among the differentially expressed genes we observed the upregulation of Th17 related genes and of type I interferon (IFN inducible genes. FACS analysis confirmed the Th17 polarization. Moreover, the synovial trascriptome shows gene clusters (bone remodeling, angiogenesis and inflammation involved in the pathogenesis of PsA. Interestingly 90 genes are modulated in both compartments (PBC and synovium suggesting that signature pathways in PBC mirror those of the inflamed synovium. Finally the osteoactivin gene was upregulared in both PBC and synovial biopsies and this finding was confirmed by the detection of high levels of osteoactivin in PsA sera but not in other inflammatory arthritides.We describe the first analysis of the trancriptome in paired synovial tissue and PBC of patients with PsA. This study strengthens the hypothesis that PsA is of autoimmune origin since the coactivity of IFN and Th17 pathways is typical of autoimmunity. Finally these findings have allowed the identification of a possible disease biomarker, osteoactivin, easily detectable in PsA serum.

  6. Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks

    DEFF Research Database (Denmark)

    Andersen, Martin; Boesen, Mikael; Ellegaard, Karen

    2014-01-01

    (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model. RESULTS: Tissue samples from......INTRODUCTION: Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study...... procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema...

  7. Diagnosing Septic Arthritis in the Synovial White Cell Count "Gray Zone".

    Science.gov (United States)

    Ruzbarsky, Joseph J; Gladnick, Brian P; Dodwell, Emily

    2016-07-01

    Differentiating septic arthritis of the pediatric hip from other causes of hip pain and effusion continues to present a diagnostic challenge for the clinician. Although septic arthritis traditionally has been reported to have a synovial white blood cell count of 75,000 cells/mm3 or greater, lower counts can be seen in this condition. In cases where a synovial sample has been obtained and the cell count falls in the intermediate range between 25,000 and 75,000 cells/mm(3), it is unclear what proportion of these cases may be truly septic hips. In this evidence-based review, we examine Heyworth et al's study focusing on the predictive value of this intermediate white cell count range in a Lyme-endemic region.

  8. Identification of candidate synovial membrane biomarkers after Achyranthes aspera treatment for rheumatoid arthritis.

    Science.gov (United States)

    Zheng, Wen; Lu, Xianghong; Fu, Zhirong; Zhang, Lin; Li, Ximin; Xu, Xiaobao; Ren, Yina; Lu, Yongzhuang; Fu, Hongwei; Tian, Jingkui

    2016-03-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main symptom is a heightened inflammatory response in synovial tissues. To verify the anti-arthritic activities of Achyranthes aspera and its possible therapy-related factors on the pathogenesis of RA, the saponins in A. aspera root were isolated and identified to treat the collagen-induced arthritis (CIA) rats. Phytochemical analysis isolated and identified methyl caffeate, 25-S-inokosterone, 25-S-inokosterone β-D-glucopyranosyl 3-(O-β-D-glucopyranosyloxy)-oleanolate, and β-D-glucopyranosyl 3-(O-β-D-galactopyranosyl (1→2)(O-β-D-glucopyranosyloxy)-oleanolate as main compounds in the root of A. aspera. Proteomics was performed to determine the differentially expressed proteins in either inflamed or drug-treated synovium of CIA rats. Treatment resulted in dramatically decreased paw swelling, proliferation of inflammatory cells, and bone degradation. Fibrinogen, procollagen, protein disulfide-isomerase A3, and apolipoprotein A-I were all increased in inflamed synovial tissues and were found to decrease when administered drug therapy. Furthermore, Alpha-1-antiproteinase and manganese superoxide dismutase were both increased in drug-treated synovial tissues. The inhibition of RA progression shows that A. aspera is a promising candidate for future treatment of human arthritis. Importantly, the total saponins found within A. aspera are the active component. Finally, autoantigens such as fibrinogen and collagen could act as inducers of RA due to their aggravation of inflammation. Given this, it is possible that the vimentin and PDIA3 could be the candidate biomarkers specific to Achyranthes saponin therapy for rheumatoid arthritis in synovial membrane.

  9. Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis

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    Ewa Tuszkiewicz-Misztal

    2011-04-01

    Full Text Available Childhood chronic arthritis of unknown etiology is known collectively as juvenile idiopathic arthritis (JIA and consists of heterogeneous subtypes with unique clinical patterns of disease. JIA is the commonest rheumatic disease in children and may still result in significant disability, with joint deformity, growth impairment, and persistence of active arthritis into adulthood. Basic research is rather focused on rheumatoid arthritis, and this lead to small number of publications considering JIA. In this study we examine, by flow cytometry, the expression of dendritic cells (DCs in the peripheral blood and synovial fluid of children with active JIA in a group of 220 patients. We reveal a significant decrease in the percentage of immature DCs in the blood of patients compared to control children. Surprisingly, we found higher percentages of mature circulating dendritic cells. Both populations of DCs, immature and mature, were accumulated in patients’ synovial fluid. We also confirmed the presence of CD206+/CD209+ in JIA samples, which can represent a population of macrophages with dendritic cells morphology. Our results support the thesis that dendritic cells are crucial in the induction and maintenance of autoimmune response and local inflammation during juvenile idiopathic arthritis. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 188–199

  10. 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 (p<0.05) and chemokines CCL2, CXCL10 and CXCL13 (p<0.05). No overall changes were observed in synovial inflammation score or the presence of T cells, B cells or macrophages. Changes in synovial phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month clinical responses (p<0.002). Tofacitinib significantly decreased plasma CXCL10 (p<0.005) at Day 28 compared with placebo. Conclusions Tofacitinib 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

  11. Chikungunya virus exploits miR-146a to regulate NF-κB pathway in human synovial fibroblasts.

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    Sakthi Priya Selvamani

    Full Text Available OBJECTIVES: Chikungunya virus causes chronic infection with manifestations of joint pain. Human synovial fibroblasts get infected with CHIKV and could lead to pro-inflammatory responses. MicroRNAs have potentials to regulate the gene expression of various anti-viral and pro-inflammatory genes. The study aims to investigate the role of miR-146a in modulation of inflammatory responses of human synovial fibroblasts by Chikungunya virus. METHODS: To study the role of miR-146a in CHIKV pathogenesis in human synovial cells and underlying inflammatory manifestations, we performed CHIKV infection in primary human synovial fibroblasts. Western blotting, real-time PCR, luciferase reporter assay, overexpression and knockdown of cellular miR-146a strategies have been employed to validate the role of miR-146a in regulation of pro-inflammatory NF-κB pathway. RESULTS: CHIKV infection induced the expression of cellular miR-146a, which resulted into down-regulation of TRAF6, IRAK1, IRAK2 and increased replication of CHIKV in human synovial fibroblasts. Exogenous expression of miR-146a in human synovial fibroblasts led to decreased expression of TRAF6, IRAK1, IRAK2 and decreased replication of CHIKV. Inhibition of cellular miR-146a by anti-miR-146a restored the expression levels of TRAF6, IRAK1 and IRAK2. Downregulation of TRAF6, IRAK1 and IRAK2 led to downstream decreased NF-κB activation through negative feedback loop. CONCLUSION: This study demonstrated the mechanism of exploitation of cellular miR-146a by CHIKV in modulating the host antiviral immune response in primary human synovial fibroblasts.

  12. Glucocorticoid receptors in fibroblasts from synovial tissue. Changes during the inflammatory process. Preliminary results.

    Science.gov (United States)

    Damon, M; Rabier, M; Loubatiere, J; Blotman, F; Crastes de Paulet, A

    1986-03-01

    There is known to be a significant correlation between the number of glucocorticoid receptors in tissues and their anti-inflammatory effect. In this work, the specific binding of glucocorticoids was studied in inflammatory fibroblasts. Human fibroblasts were obtained from the knee joint of a rheumatoid patient undergoing surgery; experimental fibroblasts were from rat granulomas. The same study was carried out in quiescent synovial fibroblasts from a healthy subject (post-traumatic amputation) and from rat subcutaneous conjunctive tissue. Fibroblasts were obtained by explant cultures and subcultures in monolayers. The stimulation state of cells was evaluated by the amounts of PGE2 and PGF2 alpha released into the culture media. Analysis of the proportions of steroid bound to whole cells showed evidence of specific glucocorticoid receptors in all fibroblasts. Their number was three times higher in cells from inflammatory tissues than from controls. This increased number of receptors in inflammatory cells could be the result of the action of one or more mediators that promote their biosynthesis.

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

    Science.gov (United States)

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

    2017-03-01

    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.

  14. Effect of NK-22 cells in the synovial fluid of patients with rheumatoid arthritis on the proliferation of fibroblast-like synoviocytes and its possible mechanism%类风湿关节炎患者滑液NK-22细胞对成纤维样滑膜细胞增殖的影响及其机制研究

    Institute of Scientific and Technical Information of China (English)

    任洁; 李娟; 冯知涛; 吕卓

    2011-01-01

    Objective To investigate the effect of NK-22 cells isolated from the synovial fluid (SF) of patients with rheumatoid arthritis (RA) on the proliferation of fibroblast-like synoviocytes and explore its possible mechanism. Methods The proportions of NK-22 cells in the peripheral blood (PB) and the SF of 20 RA patients and 20 healthy individuals were determined by flow cytometry. NK-22 cells in the SF sorted by flow cytometry were cultured for two weeks followed by a 4-h stimulation with 20 ng/ml phorbol 12-myristate 13-acetate and 0.5 junol/L ionomycin. The culture supernatant of NK-22 cells was then harvested, in which the levels of IL-22 and TNF-ct were measured by ELISA. The fibroblast-like synoviocytes were exposed to the culture supernatant for 24, 48, 72, and 96 h, and the changes in the cell proliferation were detected by MTT assay. Results RA patients showed a significantly greater proportion of NK-22 cells in both the SF and PB than the normal control subjects (P<0.05). NK-22 cells sorted by flow cytometry reached a purity exceeding 90%, and the levels of IL-22 and TNF-a in the culture supernatant of NK-22 cells cultured for two weeks were 941.16 pg/ml and 368.1 pg/ml, respectively. The culture supernatant of NK-22 cells caused a rapid proliferation of the fibroblast-like synoviocytes at 24, 48, 72, and 96 h after the exposure. Conclusion NK-22 cells in the SF of RA patients can promote the proliferation of fibroblast-like synoviocytes possibly due to the capacity of NK-22 cells to produce IL-22 and TNF-a.%目的 探讨类风湿关节炎患者滑液NK-22细胞对成纤维样滑膜细胞增殖的影响及其可能机制.方法 采用流式细胞术检测20例RA患者及20例健康对照外周血(peripheral blood,PB)、10例RA患者滑液(synovialfluid,SF)中NK-22细胞(NKp44+CCR6+NK细胞)比例.流式细胞术分选滑液NK-22细胞,鉴定细胞纯度;体外悬浮培养2周,佛波酯(PMA)(20ng/nl)和ionomycin(0.5 μmo1/L)刺激后NK-22细胞培养上清液

  15. Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis.

    Science.gov (United States)

    Kruithof, Elli; Baeten, Dominique; De Rycke, Leen; Vandooren, Bernard; Foell, Dirk; Roth, Johannes; Cañete, Juan D; Boots, Annemieke M; Veys, Eric M; De Keyser, Filip

    2005-01-01

    At present only few biological data are available to indicate whether psoriatic arthritis (PsA) is part of the spondyloarthropathy (SpA) concept, whether it is a separate disease entity or a heterogeneous disease group with oligoarticular/axial forms belonging to SpA and polyarticular forms resembling rheumatoid arthritis (RA). To address this issue with regard to peripheral synovitis, we compared the synovial characteristics of PsA with those of ankylosing spondylitis (AS)/undifferentiated SpA (USpA) and RA, and compared the synovium of oligoarticular versus polyarticular PsA. Synovial biopsies were obtained from patients with RA, nonpsoriatic SpA (AS + USpA), and oligoarticular and polyarticular PsA. The histological analysis included examination(s) of the lining layer thickness, vascularity, cellular infiltration, lymphoid aggregates, plasma cells and neutrophils. Also, we performed immunohistochemical assessments of CD3, CD4, CD8, CD20, CD38, CD138, CD68, CD163, CD83, CD1a, CD146, alphaVbeta3, E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, S100A12, intracellular citrullinated proteins and major histocompatibility complex (MHC)-human cartilage (HC) gp39 peptide complexes. Comparing SpA (PsA + AS + USpA) with RA, vascularity, and neutrophil and CD163+ macrophage counts were greater in SpA (P polyarticular PsA, no significant differences were noted. Moreover, intracellular citrullinated proteins and MHC-HC gp39 peptide complexes, which are specific markers for RA, were observed in neither oligoarticular nor polyarticular PsA. Taken together, these data indicate that the synovial histopathology of PsA, either oligoarticular or polyarticular, resembles that of other SpA subtypes, whereas both groups can be differentiated from RA on the basis of these same synovial features, suggesting that peripheral synovitis in PsA belongs to the SpA concept.

  16. 类风湿关节炎成纤维滑膜细胞端粒保护蛋白TPP1及POT1 mRNA表达的研究%Expression of TPP1 and POT1 mRNA in synovial fibroblasts of patients with rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    青玉凤; 周京国; 袁国华; 刘青松; 蒋莉; 杨其彬

    2009-01-01

    Objective To study the expression of telomeric protein TPP1 and POT1 mRNA and its association with disease stages and clinical manifestations in synovial fibroblast (SFs) from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy individuals in order to explore the mechanisms of pathogenesis of RA.Methods SFs were cultured in vitro, and TPP1 and POT1 mRNA were measured using real-time polymerase chain reaction (RT-PCR) in SFs.The expression of TPP1 and POT1 mRNA in SFs were compared between patients with RA (n=28), patients with OA (n=15), and healthy individuals (n=3).Results The expression of TPP1 and POT1 mRNA in SFs in RA patients was significantly decreased when compared to OA patients and healthy individuals (P<0.05).The expression of TPP1 mRNA was found to be correlated negatively with anti-CCP antibodies and rheumatoid factor;but not correlated with Disease Active Score (DAS), Serum C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR).The expression of POT1 mRNA was not correlated with antibodies, rheumatoid factor, DAS, CRP and ESR.Conclusion Expression of TPP1 and POT1 mRNA in RA SFs is decreased significantly than that in OA and normal SFs.The low expression of TPP1 mRNA may lead to dysfunction of telomere, and may be involved in the pathogenesis of RA and contributes to cartilage and bone destruction.%目的 检测端粒保护蛋白TPP1及POT1 mRNA在类风湿关节炎(RA)、骨关节炎(OA)患者及健康人成纤维样滑膜细胞(SFs)的表达水平.探讨其在RA发病机制中可能的作用.方法 体外培养SFs,用实时荧光定量聚合酶链反应(PCR)方法检测28例RA、15例OA和3名健康者SFs TPP1,POT1mRNA的表达水平,并与疾病活动性等临床指标进行分析.结果 TPP1,POT1 mRNA在RA SFs组的表达低于OA组及健康对照组(P均<0.05).OA组和健康对照组间差异无统计学意义.TPP1 mRNA在RA SFs的表达水平与RA患者抗环瓜氨酸肽(CCP)抗体及类风

  17. Epigenetic modifications of interleukin-6 in synovial fibroblasts from osteoarthritis patients

    Science.gov (United States)

    Yang, Fei; Zhou, Song; Wang, Chuandong; Huang, Yan; Li, Huiwu; Wang, You; Zhu, Zhenan; Tang, Jian; Yan, Mengning

    2017-01-01

    Osteoarthritis (OA) is the most common degenerative disease of the synovial joint. The synovial membrane is responsible for the inflammatory reaction leading to the secretion of macrophage-derived pro-inflammatory cytokines, such as IL-6. Suppressing IL-6 over-expression in synovial fibroblasts (SF) is a promising method to prevent OA development and progression, in which the prerequisite is the elucidation of the molecular mechanisms underlying IL-6 over-expression in SF. Currently, there are few reports concerning epigenetic modifications in IL-6 in OA SF. In the present study, we attempted to investigate this phenomenon. SF over-expressing IL-6 was collected from OA patients. DNA hypomethylation and histone hyperacetylation were observed in the IL-6 promoter regions in OA SF compared with normal SF. No differences in the status of H3K9 di-methylation, H3K27 tri-methylation and H3K4 tri-methylation were observed in the IL-6 promoter regions between normal and OA SF. DNA (cytosine-5-)-methyltransferase 3 alpha (Dnmt3a) overexpression and anacardic acid (histone acetyltransferase inhibitor) treatment increased DNA methylation and decreased histone acetylation in the IL-6 promoter, and IL-6 over-expression in OA SF was suppressed. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic methods to treat OA. PMID:28262826

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

    Directory of Open Access Journals (Sweden)

    Ichiro Miki

    2007-09-01

    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.

  19. Evaluation of apoptosis induction in human peripheral blood mononuclear cells and synovial cells in patients with rheumatoid arthritis.

    Science.gov (United States)

    Demian, Soheir R; Abo-Shousha, Seham A; Sultan, Hussein E; Zarka, Wael El

    2005-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory destructive disease involving the joint and characterized by T-lymphocyte accumulation within the synovial compartment. It is dominated by the presence of macrophages, plasma cells and synovial fibroblasts which are the main pathogenic factors leading to the destruction of bone and cartilage. The survival of these cells may be promoted by inadequate apoptosis leading to synovial hyperplasia. So, the aim of the present study was to evaluate the apoptosis levels before and after induction of apoptosis using anti-Fas mAb, both in peripheral blood (PB) and synovial fluid (SF) infiltrating mononuclear cells (MCs) of patients with RA. CD4+ T cell subsets and cell survival assays were also done to investigate correlations between these parameters. The study was conducted on 15 patients with RA, 10 individual volunteers as a control group and 10 patients with osteoarthritis (OA) as a control group for SF evaluations (have defective Fas expression on their cells). Results of this work revealed that in vitro induction of apoptosis by anti-Fas mAb resulted in increase of: percent (%) reduction of cell viability in PBMCs and SFMCs, % reduction of CD4+ T cell subsets and apoptotic cell % in all studied groups than before induction. The increase in the three parameters is only significant in SF of RA group compared to PB while it is non significant in OA group due to the defective Fas expression on OA cells. Our results also showed a significant positive correlation between CD4+ T cell and viability percentages before induction of apoptosis in SF of RA and between apoptosis levels and CD4+ T cell percentage after induction of apoptosis in the SF of RA group. In conclusion, activated T cells infiltrating SF of RA patients have functional Fas antigen which enable them to undergo in vitro apoptosis using anti-Fas mAb. The cytotoxicity of which is more specific to local lesion such as SF of RA patients suggesting that local

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

    OpenAIRE

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Kwiatkowska, Brygida; Zaniewicz-Kaniewska, Katarzyna; Warczyńska, Agnieszka

    2012-01-01

    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 a...

  1. Staphylococcal Enterotoxin A Detection from Rheumatoid Arthritis Patients’ Blood and Synovial Fluid

    Science.gov (United States)

    Ataee, Ramezan Ali; Kahani, Mahboobeh Sadat; Alishiri, Gholam Hossein; Ahamadi, Zyenab

    2016-01-01

    Introduction Direct detection of microbial super antigens in synovial fluid of patients with rheumatoid arthritis may be able to guide to the design of cost-effective therapies. The purpose of this study was to assess the existence of Staphylococcal enterotoxin A (superantigen A) in the synovial fluid of patients with RA by the PCR and ELISA methods. Methods This experimental study was conducted on the synovial fluid of 103 RA patients from Baqiyatallah University of Medical Sciences’ Rheumatology Clinic in Tehran, Iran in 2011–2014. Bacterial cultures, polymerase chain reaction with specific primer pairs and enzyme-linked immunosorbent assay (ELISA) methods were used. The PCR products were subjected to sequence as a confirmatory molecular method results. The data were descriptively analyzed by SPSS Version 19. Results The bacteriological study result indicated that, in four cases (3.8%) of the patients, bacterial strains were isolated. The result of PCR molecular method for staphylococcal enterotoxin A gene showed that, 42 of the patients (40.7%) tested positive for the ent A gene. The results of ELISA were positive for staphylococcal enterotoxin A (superantigen A) in 51 cases (49.51%) of the patients’ synovial fluids. The results indicated that the possibility of detecting superantigen A in the SF of RA patients, but the origin of the enterotoxin A gene remained unknown. Conclusions The findings of this study may be able to alter the actual theory on the pathogenesis, diagnosis, and treatment of RA patients. In addition, the results have shown the probability of an endogenous origin for the involved superantigen A in RA patients’ synovial fluids. PMID:27053990

  2. Global metabolite profiling of synovial fluid for the specific diagnosis of rheumatoid arthritis from other inflammatory arthritis.

    Directory of Open Access Journals (Sweden)

    Sooah Kim

    Full Text Available Currently, reliable biomarkers that can be used to distinguish rheumatoid arthritis (RA from other inflammatory diseases are unavailable. To find possible distinctive metabolic patterns and biomarker candidates for RA, we performed global metabolite profiling of synovial fluid samples. Synovial fluid samples from 38 patients with RA, ankylosing spondylitis, Behçet's disease, and gout were analyzed by gas chromatography/time-of-flight mass spectrometry (GC/TOF MS. Orthogonal partial least-squares discriminant and hierarchical clustering analyses were performed for the discrimination of RA and non-RA groups. Variable importance for projection values were determined, and the Wilcoxon-Mann-Whitney test and the breakdown and one-way analysis of variance were conducted to identify potential biomarkers for RA. A total of 105 metabolites were identified from synovial fluid samples. The score plot of orthogonal partial least squares discriminant analysis showed significant discrimination between the RA and non-RA groups. The 20 metabolites, including citrulline, succinate, glutamine, octadecanol, isopalmitic acid, and glycerol, were identified as potential biomarkers for RA. These metabolites were found to be associated with the urea and TCA cycles as well as fatty acid and amino acid metabolism. The metabolomic analysis results demonstrated that global metabolite profiling by GC/TOF MS might be a useful tool for the effective diagnosis and further understanding of RA.

  3. Abnormal PTPN11 enhancer methylation promotes rheumatoid arthritis fibroblast-like synoviocyte aggressiveness and joint inflammation

    Science.gov (United States)

    Maeshima, Keisuke; Stanford, Stephanie M.; Hammaker, Deepa; Sacchetti, Cristiano; Zeng, Li-fan; Ai, Rizi; Zhang, Vida; Boyle, David L.; Aleman Muench, German R.; Feng, Gen-Sheng; Whitaker, John W.; Zhang, Zhong-Yin; Wang, Wei; Bottini, Nunzio; Firestein, Gary S.

    2016-01-01

    The PTPN11 gene, encoding the tyrosine phosphatase SHP-2, is overexpressed in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) compared with osteoarthritis (OA) FLS and promotes RA FLS invasiveness. Here, we explored the molecular basis for PTPN11 overexpression in RA FLS and the role of SHP-2 in RA pathogenesis. Using computational methods, we identified a putative enhancer in PTPN11 intron 1, which contained a glucocorticoid receptor–binding (GR-binding) motif. This region displayed enhancer function in RA FLS and contained 2 hypermethylation sites in RA compared with OA FLS. RA FLS stimulation with the glucocorticoid dexamethasone induced GR binding to the enhancer and PTPN11 expression. Glucocorticoid responsiveness of PTPN11 was significantly higher in RA FLS than OA FLS and required the differentially methylated CpGs for full enhancer function. SHP-2 expression was enriched in the RA synovial lining, and heterozygous Ptpn11 deletion in radioresistant or innate immune cells attenuated K/BxN serum transfer arthritis in mice. Treatment with SHP-2 inhibitor 11a-1 reduced RA FLS migration and responsiveness to TNF and IL-1β stimulation and reduced arthritis severity in mice. Our findings demonstrate how abnormal epigenetic regulation of a pathogenic gene determines FLS behavior and demonstrate that targeting SHP-2 or the SHP-2 pathway could be a therapeutic strategy for RA. PMID:27275015

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

    Directory of Open Access Journals (Sweden)

    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.

  5. PPAR-gamma ligands modulate effects of LPS in stimulated rat synovial fibroblasts.

    Science.gov (United States)

    Simonin, Marie-Agnès; Bordji, Karim; Boyault, Sandrine; Bianchi, Arnaud; Gouze, Elvire; Bécuwe, Philippe; Dauça, Michel; Netter, Patrick; Terlain, Bernard

    2002-01-01

    This work demonstrated the constitutive expression of peroxisome proliferator-activated receptor (PPAR)-gamma and PPAR-alpha in rat synovial fibroblasts at both mRNA and protein levels. A decrease in PPAR-gamma expression induced by 10 microg/ml lipopolysaccharide (LPS) was observed, whereas PPAR-alpha mRNA expression was not modified. 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) dose-dependently decreased LPS-induced cyclooxygenase (COX)-2 (-80%) and inducible nitric oxide synthase (iNOS) mRNA expression (-80%), whereas troglitazone (10 microM) only inhibited iNOS mRNA expression (-50%). 15d-PGJ(2) decreased LPS-induced interleukin (IL)-1 beta (-25%) and tumor necrosis factor (TNF)-alpha (-40%) expression. Interestingly, troglitazone strongly decreased TNF-alpha expression (-50%) but had no significant effect on IL-1 beta expression. 15d-PGJ(2) was able to inhibit DNA-binding activity of both nuclear factor (NF)-kappa B and AP-1. Troglitazone had no effect on NF-kappa B activation and was shown to increase LPS-induced AP-1 activation. 15d-PGJ(2) and troglitazone modulated the expression of LPS-induced iNOS, COX-2, and proinflammatory cytokines differently. Indeed, troglitazone seems to specifically target TNF-alpha and iNOS pathways. These results offer new insights in regard to the anti-inflammatory potential of the PPAR-gamma ligands and underline different mechanisms of action of 15d-PGJ(2) and troglitazone in synovial fibroblasts.

  6. 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.

  7. 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.

  8. Occasional presence of herpes viruses in synovial fluid and blood from patients with rheumatoid arthritis and axial spondyloarthritis.

    Science.gov (United States)

    Burgos, Rubén; Ordoñez, Graciela; Vázquez-Mellado, Janitzia; Pineda, Benjamín; Sotelo, Julio

    2015-10-01

    Viral agents have been suspected as participants of immune-mediated disorders. In the case of rheumatic diseases, the synovial joint cavity represents a secluded area of inflammation which could harbor etiological agents. We analyzed by polymerase chain reaction the possible presence of DNA from various herpes viruses in blood and synovial fluid from patients with either rheumatoid arthritis (n = 18), axial spondyloarthritis (n = 11), or osteoarthritis (n = 8). Relevant findings were as follows: DNA from varicella zoster virus was found in synovial fluid but not in blood mononuclear cells from 33 % of patients with rheumatoid arthritis and in 45 % of patients with axial spondyloarthritis but not in patients with osteoarthritis. Also, DNA from herpes simplex viruses 1 and 2 was found both in the blood and in the synovial fluid from 33 % of patients with rheumatoid arthritis. Our results indicate the occasional presence of DNA from herpes viruses in patients with rheumatoid arthritis or with axial spondyloarthritis. However, these findings might represent a parallel epiphenomenon of viral activation associated either with immunosuppressive therapy or with primary immune disturbances, rather than the etiological participation of herpes viruses in these disorders.

  9. 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

    OBJECTIVE. Levels of beta 2-microglobulin and modified beta 2-microglobulin (Des-Lys58-beta 2m) were measured in serum and synovial fluids from patients with rheumatoid arthritis (RA) and other inflammatory joint disorders using rabbit antisera prepared against the beta 2m peptide VEHSDLSFS...

  10. Identification of novel autoantigen in the synovial fluid of rheumatoid arthritis patients using an immunoproteomics approach.

    Directory of Open Access Journals (Sweden)

    Sagarika Biswas

    Full Text Available Rheumatoid arthritis (RA is a chronic, autoimmune and inflammatory joint disease with a poorly understood etiology. Despite widespread diagnostic use of anti-citrullinated protein antibodies and rheumatoid factor proteins there is a strong demand for novel serological biomarkers to improve the diagnosis this disease. The present study was aimed to identify novel autoantigens involved in rheumatoid arthritis (RA pathogenesis through immune-proteomic strategy. Synovial fluid samples from clinically diagnosed RA patients were separated on two-dimensional gel electrophoresis (2-DE. Samples from patients with non-RA rheumatisms (osteoarthritis and trauma were used as controls. Immunoreactive proteins were spotted by Western blotting followed by identification through Q-TOF mass spectrometer analysis. Forty Western blots were generated using plasma from ten individual RA patients and 33 reactive spots were identified, 20 from the high molecular weight (HMW gel and 13 from the low molecular weight (LMW gel. Among the 33 common immunogenic spots, 18 distinct autoantigens were identified, out of which 14 are novel proteins in this context. Expression analysis of five important proteins, vimentin, gelsolin, alpha 2 HS glycoprotein (AHSG, glial fibrillary acidic protein (GFAP, and α1B-glycoprotein (A1BG by Western blot analysis using their specific antibodies revealed their higher expression in RA synovial fluid as compared to non-RA samples. Recombinantly expressed GFAP and A1BG protein were used to develop an in-house ELISA to quantify the amount of autoantibodies in the RA patients. RA patients revealed an increase in the expression of GFAP and A1BG in the plasma as compared to osteoarthritis patients. Therefore, GFAP and A1BG can be proposed as potential new autoantigens of diagnostic importance for RA subjects. Further characterization of these proteins in rheumatoid arthritis will be helpful in understanding the role of these proteins in the disease

  11. Anti-interleukin-6 receptor antibody influencing expresses of receptor activator of NF-κB ligand in rheumatoid arthritis synovial fibroblasts%白细胞介素6受体抗体对类风湿关节炎滑膜成纤维细胞核因子-κB受体激活因子配体表达影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    蔡月明; 陶可; 曾晖; 叶静; 张芳婷; 王庆文

    2013-01-01

    Objective To investigate the influence of interleukin-6 receptor (IL-6R-Ab) antibody on proliferation and expression of nuclear factor-κB-activating factor receptor ligand (RANKL) in rheumatoid arthritis(RA) synovial fibroblasts.Methods Synovial tissue obtained from laparoscopic surgery,and then digested and subcultured.The experiment was divided into 4 groups according to different cultural conditions,methotrexate (MTX) group,IL-6R a(n)tibody (IL-6R-Ab) group,IL-6R antibody combined MTX (combination )group,and the control group respectively.Cells growth inhibition and medicine toxicity of IL-6R antibody,MTX in RA synovial fibroblasts were measured by cell counting kit-8 (CCK-8).FQ-PCR was applied to detect the expression of RANKL mRNA.Results The results of CCK-8 test showed that the cells proliferation in the presence of MTX,1L-6R-Ab and combination group were fairly lower than that of in the control group (F =54.64,P <0.05),and IL-6R antibody combined MTX group was significantly inhibited (P < 0.01);comparing to the MTX group,there was no significant difference in IL-6R antibody group.ELISA tests results indicated that compared to the MTX group,expression of RANKL in IL-6R-Ab and IL-6R-Ab combined MTX group all decreased (F =32.17,P < 0.05).Further more,the expression in IL-6R antibody combined MTX group is the lowest (P < 0.01).Results of FQ-PCR indicated that compared to the control cells,the expression of RANKL mRNA in other three groups were inhibited (P < 0.05).Compared to the MTX group or IL-6R-Ab group,the expression of RANKL mRNA was inhibited in combination group obviously (P < 0.05).Conclusion IL-6R-Ab alone or combinate to MTX could significantly inhibit the proliferating activities of RA synovial fibroblasts and significantly down regulated the expression of RANKL,which might provide theoretical basis of cellular and molecular biology for treatment of RA.%目的 探讨白细胞介素6受体抗体(IL-6R-Ab)对类风湿关节炎(RA)滑膜

  12. 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.

  13. Ultrasound colour Doppler is associated with synovial pathology in biopsies from hand joints in rheumatoid arthritis patients

    DEFF Research Database (Denmark)

    Andersen, Martin; Ellegaard, Karen; Hebsgaard, Josephine B;

    2014-01-01

    OBJECTIVES: Little is known regarding the association between ultrasound-determined pathological synovial blood flow and synovial pathology in rheumatoid arthritis (RA). We therefore examined the association between colour Doppler ultrasound imaging and synovitis assessed by histopathology......-3). Data were clustered within patients, thus a linear mixed model was applied for the statistical tests. Parsimony in the statistical models was achieved omitting covariates from the model in the case of what was judged no statistical significance (p>0.1). RESULTS: Doppler colour fraction showed...

  14. Soluble P-selectin levels in synovial fluid and serum from patients with psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    G. Valesini

    2011-09-01

    Full Text Available Objective: P-selectin is an adhesion molecule expressed by activated endothelial cells and platelets favouring the leukocyte adherence to microvascular endothelium. A soluble form of this molecule has been described, whose serum levels were found to be elevated and correlate with disease activity in rheumatoid arthritis (RA patients. Aim of this study was to determine soluble P-selectin levels in synovial fluid (SF and serum from patients with psoriatic arthritis (PsA, where it has never been investigated, to define its involvement in PsA synovial damage. Methods: we analysed, by ELISA, soluble P-selectin serum and SF levels in 100 patients presenting a knee joint effusion: 38 of them presented PsA, 40 RA and 22 osteoarthritis (OA. We examined the main clinical and laboratory parameters of these patients. Soluble P-selectin serum levels were also detected in 15 healthy subjects. Results: soluble P-selectin SF levels were significantly higher in PsA and RA patients respect to OA subjects. Soluble P-selectin SF levels were lower than those found in serum and the SF/serum ratio was higher in PsA and RA patients respect to OA. Soluble P-selectin serum levels were not significantly different among patients and controls. No correlation was found between SF and serum levels of soluble P-selectin and the main clinical parameters. Conclusions: our study of soluble P-selectin in PsA reveals a prominent local role of this molecule, with no differences respect to RA. Histological findings may be of help in understanding the role of this adhesion molecule in PsA.

  15. Interleukin-21 induces migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis.

    Science.gov (United States)

    Xing, R; Jin, Y; Sun, L; Yang, L; Li, C; Li, Z; Liu, X; Zhao, J

    2016-05-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone erosion. Fibroblast-like synoviocytes (FLS) play a pivotal role in RA pathogenesis through aggressive migration and matrix invasion, and certain proinflammatory cytokines may affect synoviocyte invasion. Whether interleukin (IL)-21 influences this process remains controversial. Here, we evaluated the potential regulatory effect of IL-21 on the migration, invasion and matrix metalloproteinase (MMP) expression in RA-FLS. We found that IL-21 promoted the migration, invasion and MMP (MMP-2, MMP-3, MMP-9, MMP-13) production in RA-FLS. Moreover, IL-21 induced activation of the phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathways, and blockage of these pathways [PI3K/protein kinase B (AKT) inhibitor LY294002, STAT-3 inhibitor STA-21 and ERK1/2 inhibitor PD98059] attenuated IL-21-induced migration and secretion of MMP-3 and MMP-9. In conclusion, our results suggest that IL-21 promotes migration and invasion of RA-FLS. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of RA.

  16. 体外实验经典活化型巨噬细胞抑制类风湿关节炎滑膜成纤维细胞增殖%Classically activated macrophage inhibits rheumatoid arthritis fibroblast-like synovial proliferation

    Institute of Scientific and Technical Information of China (English)

    樊莎莎; 宗明; 陆英; 卢添宝; 崔显念; 范列英

    2015-01-01

    目的 研究经典活化型巨噬细胞(M1)对RA滑膜成纤维细胞(FLS)和对照组OA-FLS增殖的影响,为进一步研究巨噬细胞在RA疾病进展中的作用奠定基础.方法 采用脂多糖和IFN-γ体外诱导人单核细胞(THP-1)为M1,流式细胞术(FCM)检测M1表面特异性标志分子HLA-DR和CD197表达.transwell非接触式共培养M1和RA-FLS、OA-FLS,结晶紫染色法观察共培养48 h后RA-FLS、OA-FLS的增殖情况.MTS法检测M1分泌细胞因子对RA-FLS、OA-FLS增殖的影响.ELISA检测单独培养体系及共培养体系细胞培养上清中细胞因子TNF-α和IL-12的变化.采用配对t检验比较分析.结果 脂多糖和IFN-γ诱导THP-1为M1后,M1表面标记分子CD197和HLA-DR阳性率为78.25%和87.96%.RA-FLS、OA-FLS与M1共培养48 h后,RA-FLS、OA-FLS增殖受到明显抑制,共培养组显微镜下每视野RA-FLS、OA-FLS细胞数分别为(64±30)、(85 ±23),RA-FLS、OA-FLS单独培养组分别为(467±87)、(263±78),差异有统计学意义(t=7.459,3.791;P均<0.05).M1与FLS共培养对RA-FLS、OA-FLS的增殖有明显抑制作用,差异有统计学意义(t=-7.155,-8.111;P均<0.05).RA-FLS单独培养组和M1与RA-FLS共培养组培养上清中TNF-α的浓度分别是(0.024±0.011) ng/ml、(0.832±0.241) ng/ml,IL-12浓度分别为(0.033±0.015) ng/ml、(0.372±0.122) ng/ml;OA-FLS单独培养组和M1与OA-FLS共培养组培养上清中TNF-α的浓度分别是(0.031 ±0.017) ng/ml、(0.854±0.323) ng/ml,IL-12浓度分别为(0.012±0.009) ng/ml、(0.373±0.144) ng/ml;共培养组TNF-α和IL-12浓度均明显升高,差异均有统计学意义(t=-4.997,-4.777,-4.407,-4.334;P均<0.05),RA组与OA组的结果一致.结论 M1与RA-FLS、OA-FLS共培养后,显著抑制RA-FLS、OA-FLS增殖,可能与共培养上清中TNF-α和IL-12的增加有关.%Objective To investigate the influence of classically activated macrophage (M1) on the proliferation of rheumatoid arthritis (RA) fibroblast-like synovial (FLS) and

  17. Adenosine monophosphate-activated protein kinase activation and suppression of inflammatory response by cell stretching in rabbit synovial fibroblasts.

    Science.gov (United States)

    Kunanusornchai, Wanlop; Muanprasat, Chatchai; Chatsudthipong, Varanuj

    2016-12-01

    Joint mobilization is known to be beneficial in osteoarthritis (OA) patients. This study aimed to investigate the effect of stretching on adenosine monophosphate-activated protein kinase (AMPK) activity and its role in modulating inflammation in rabbit synovial fibroblasts. Uniaxial stretching of isolated rabbit synovial fibroblasts for ten min was performed. Stretching-induced AMPK activation, its underlying mechanism, and its anti-inflammatory effect were investigated using Western blot. Static stretching at 20 % of initial length resulted in AMPK activation characterized by expression of phosphorylated AMPK and phosphorylated acetyl-Co A carboxylase. AMP-activated protein kinase phosphorylation peaked 1 h after stretching and declined toward resting activity. Using cell viability assays, static stretching did not appear to cause cellular damage. Activation of AMPK involves Ca(2+) influx via a mechanosensitive L-type Ca(2+) channel, which subsequently raises intracellular Ca(2+) and activates AMPK via Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ). Interestingly, stretching suppressed TNFα-induced expression of COX-2, iNOS, and phosphorylated NF-κB. These effects were prevented by pretreatment with compound C, an AMPK inhibitor. These results suggest that mechanical stretching suppressed inflammatory responses in synovial fibroblasts via a L-type Ca(2+)-channel-CaMKKβ-AMPK-dependent pathway which may underlie joint mobilization's ability to alleviate OA symptoms.

  18. Inflammatory memories: is epigenetics the missing link to persistent stromal cell activation in rheumatoid arthritis?

    NARCIS (Netherlands)

    C. Ospelt; K.A. Reedquist; S. Gay; P.P. Tak

    2011-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Synovial fibroblasts are recognized as key cells in the pathogenesis of RA since they attract and activate immune cells and produce matrix degrading enzymes. Most notably synovial fibroblasts from patients with

  19. 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.

  20. 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 (Parthritis therapy.

  1. IL-15 Expression on RA Synovial Fibroblasts Promotes B Cell Survival

    Science.gov (United States)

    Benito-Miguel, Marta; García-Carmona, Yolanda; Balsa, Alejandro; Bautista-Caro, María-Belén; Arroyo-Villa, Irene; Cobo-Ibáñez, Tatiana; Bonilla-Hernán, María Gema; de Ayala, Carlos Pérez; Sánchez-Mateos, Paloma; Martín-Mola, Emilio; Miranda-Carús, María-Eugenia

    2012-01-01

    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. PMID:22792388

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Trikatu, an herbal compound ameliorates rheumatoid arthritis by the suppression of inflammatory immune responses in rats with adjuvant-induced arthritis and on cultured fibroblast like synoviocytes via the inhibition of the NFκB signaling pathway.

    Science.gov (United States)

    Doss, Hari Madhuri; Ganesan, Ramamoorthi; Rasool, Mahaboobkhan

    2016-10-25

    The present study was designed to investigate the potential therapeutic effect of trikatu, an herbal compound and its underlying molecular mechanism in rats with adjuvant-induced arthritis (AIA). Our results indicate that trikatu (1000 mg/kg/b.wt. oral) administration suppressed the production of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1) and downregulated the mRNA expression levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17, MCP-1, receptor activator of nuclear factor kappa B ligand (RANKL), cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS)) and transcription factors (nuclear factor kappa B 65 (NFкB-p65) and activator protein-1 (AP-1)) in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA rats. Consistently, the protein expression of NFкB-p65, IL-17, TNF-α, COX-2, and RANKL was also dramatically reduced in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA rats by trikatu treatment. In addition, trikatu suppressed the expression and phosphorylation of NFкB-p65 similar to the Bay 11-7082 (NFкB inhibitor) in cultured AIA-fibroblast like synoviocytes. Furthermore, trikatu alleviated the histopathology of joint of arthritic rats. Overall, these data highlights that trikatu could be a promising alternative modality for the possible treatment of rheumatoid arthritis and other inflammatory diseases.

  4. The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs

    Science.gov (United States)

    Bombardieri, S.; Cattani, P.; Ciabattoni, G.; Di Munno, O.; Pasero, G.; Patrono, C.; Pinca, E.; Pugliese, F.

    1981-01-01

    1 The present study was undertaken to characterize the spectrum of arachidonic acid metabolites present in synovial effusions of patients with rheumatoid or psoriatic arthritis, and to compare changes in their concentration following a short-term treatment with 6α-methyl-prednisolone (6-MeP: 4-8 mg/day) or indoprofen (1.2 g/day), a nonsteroidal anti-inflammatory agent with proven synovial prostaglandin inhibitory effect. 2 Measurements of prostaglandin E2 (PGE2), thromboxane (TX) B2, 6-keto-PGF1α and PGF2α were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin-layer chromatographic analysis of the extracted immunoreactivity. 3 PGE2 and TXB2 accounted for more than 60% of the total immunoreactivity in untreated patients. The absence of any constant ratio between the different arachidonic acid metabolites detected in synovial fluid is consistent with a heterogeneous cellular origin of these compounds. 4 Indoprofen treatment was associated with a consistent reduction of synovial prostaglandin and thromboxane concentrations, ranging from 36% in the case of 6-keto-PGF1α to 90% in the case of PGE2. 5 In contrast, 6-MeP caused opposite changes on different metabolites originating via the cyclo-oxygenase pathway. Thus, 6-keto-PGF1α concentrations were reduced by 35%, PGF2α concentrations were increased by 30%, while PGE2 and TXB2 were unchanged following 6-MeP. 6 Although the mechanism(s) underlying the failure of 6-MeP to reduce synovial PGE2 and TXB2 levels are uncertain, the results of the present study clearly indicate that therapeutic doses of steroidal and nonsteroidal anti-inflammatory drugs cause quite distinct changes in arachidonic acid metabolism, which might be relevant to their specific therapeutic actions and side-effects. PMID:6895043

  5. 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

  6. Immunogenic HLA-DR-Presented Self-Peptides Identified Directly from Clinical Samples of Synovial Tissue, Synovial Fluid, or Peripheral Blood in Patients with Rheumatoid Arthritis or Lyme Arthritis.

    Science.gov (United States)

    Wang, Qi; Drouin, Elise E; Yao, Chunxiang; Zhang, Jiyang; Huang, Yu; Leon, Deborah R; Steere, Allen C; Costello, Catherine E

    2017-01-06

    Human leukocyte antigen-antigen D related (HLA-DR) molecules are highly expressed in synovial tissue (ST), the target of the immune response in chronic inflammatory forms of arthritis. Here, we used LC-MS/MS to identify HLA-DR-presented self-peptides in cells taken directly from clinical samples: ST, synovial fluid mononuclear cells (SFMC), or peripheral blood mononuclear cells (PBMC) from five patients with rheumatoid arthritis (RA) and eight with Lyme arthritis (LA). We identified 1593 non-redundant HLA-DR-presented peptides, derived from 870 source proteins. A total of 67% of the peptides identified in SFMC and 55% of those found in PBMC were found in ST, but analysis of SFMC/PBMC also revealed new antigen-presented peptides. Peptides were synthesized and examined for reactivity with the patients' PBMC. To date, three autoantigens in RA and four novel autoantigens in LA, presented in ST and/or PBMC, were shown to be targets of T- and B-cell responses in these diseases; ongoing analyses may add to this list. Thus, immunoprecipitation and LC-MS/MS can now identify hundreds of HLA-DR-presented self-peptides from individual patients' tissues or fluids with mixed cell populations. Importantly, identification of HLA-DR-presented peptides from SFMC or PBMC allows testing of more patients, including those early in the disease. Direct analysis of clinical samples facilitates identification of novel immunogenic T-cell epitopes.

  7. Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes

    Science.gov (United States)

    Garcia-Carbonell, Ricard; Divakaruni, Ajit S.; Lodi, Alessia; Vicente-Suarez, Ildefonso; Saha, Arindam; Cheroutre, Hilde; Boss, Gerry R.; Tiziani, Stefano; Murphy, Anne N.; Guma, Monica

    2016-01-01

    Objective Up-regulation of glucose metabolism has been implicated not only in tumor cell growth but also in immune cells upon activation. However, little is known about the metabolite profile in rheumatoid arthritis (RA), particularly in fibroblast-like synoviocytes (FLS). This study was undertaken to evaluate whether changes in glucose metabolism in RA FLS could play a role in inflammation and joint damage. Methods Synovium and FLS were obtained from patients with RA and patients with osteoarthritis (OA). The rate of glycolysis after stimulation of FLS with lipopolysaccharide and platelet-derived growth factor BB was measured using glycolysis stress test technology. FLS function was evaluated using a glycolysis inhibitor, 2-deoxy-D-glucose (2-DG). After stimulation of the FLS, a migration scratch assay, MTT assay, and enzyme-linked immunosorbent assay were performed to measure the effect of 2-DG on FLS migration, viability of the FLS, and cytokine secretion, respectively. IRDye 800CW 2-DG was used to assess glucose uptake in the arthritic joints and stromal cells of mice after K/BxN mouse serum transfer. The mice were injected daily, intraperitoneally, with 3-bromopyruvate (BrPa; 5 mg/kg) to assess the effect of inhibition of glycolysis in vivo. Results Compared to human OA FLS, the balance between glycolysis and oxidative phosphorylation was shifted toward glycolysis in RA FLS. Glucose transporter 1 (GLUT1) messenger RNA (mRNA) expression correlated with baseline functions of the RA FLS. Glucose deprivation or incubation of the FLS with glycolytic inhibitors impaired cytokine secretion and decreased the rate of proliferation and migration of the cells. In a mouse model of inflammatory arthritis, GLUT1 mRNA expression in the synovial lining cells was observed, and increased levels of glucose uptake and glycolytic gene expression were detected in the stromal compartment of the arthritic mouse joints. Inhibition of glycolysis by BrPa, administered in vivo

  8. 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.

  9. Fibroblast-like synoviocytes-dependent effector molecules as a critical mediator for rheumatoid arthritis: Current status and future directions.

    Science.gov (United States)

    Ganesan, Ramamoorthi; Rasool, Mahaboobkhan

    2017-01-02

    Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. Currently available biological agents and inhibitor therapy that specifically target tumor necrosis factor-α, interleukin 1β (IL-1β), IL-6, T cells, B cells, and subcellular molecules (p38 mitogen-activated protein kinase and janus kinase) cannot facilitate complete remission in all patients and are unable to cure the disease. Therefore, further potent therapeutic targets need to be identified for effective treatment and successful clinical outcomes in patients with RA. Scientific breakthroughs have brought new insights regarding fibroblast-like synoviocytes (FLS), a major constituent of the synovial hyperplasia. These play a pivotal role in RA invading cartilage and bone tissue. Currently there are no effective therapies available that specifically target these aggressive cells. Recent evidences indicate that FLS-dependent effector molecules (toll-like receptors, nodal effector molecules, hypoxia-inducible factor, and IL-17) have emerged as important mediators of RA. In this review, we discuss the pathological features and recent advances in understanding the role of FLS-dependent effector molecules in the disease onset of RA. Pharmacological inhibition of FLS-dependent effector molecules might be a promising option for FLS-targeted therapy in RA.

  10. Use of the isolator 1.5 microbial tube for culture of synovial fluid from patients with septic arthritis.

    Science.gov (United States)

    Yagupsky, P; Press, J

    1997-09-01

    Synovial fluid specimens obtained from patients with arthritis were plated onto solid media (conventional cultures) or inoculated into an Isolator 1.5 microbial tube (Isolator cultures), and the yield and time to detection of organisms were compared. Overall, 144 specimens obtained from 137 patients were processed, and 31 (21.5%) cultures obtained from 29 patients were positive by at least one method. Staphylococcus aureus was isolated from 12 patients, Streptococcus pneumoniae and Kingella kingae were isolated from 4 patients each, group G streptococci were isolated from 3 patients, Staphylococcus epidermidis and members of the family Enterobacteriaceae were isolated from 2 patients each, and Streptococcus mitis and Peptostreptococcus prevotii were isolated from 1 patient each. Overall, the causative organism was detected in 31 of 31 (100.0%) Isolator cultures and 24 of 31 (77.4%) conventional cultures (P septic arthritis.

  11. Distribution of T-cell receptor-bearing lymphocytes in the synovial membrane from patients with rheumatoid arthritis.

    Science.gov (United States)

    Chaouni, I; Radal, M; Simony-Lafontaine, J; Combe, B; Sany, J; Rème, T

    1990-12-01

    Using immunohistology and monoclonal antibodies directed to the T-cell receptor (TCR) chains, we have analysed the distribution of TCR-bearing lymphocytes within the membrane of rheumatoid arthritis (RA) patients. Alkaline phosphatase staining for TCR alpha beta-bearing lymphocytes showed a distribution paralleling that of the total T cells. Staining for the TCR gamma delta chains revealed a moderate and rather homogeneous distribution of T gamma delta lymphocytes within the RA synovium. As evidenced by simultaneous staining for alpha beta and gamma delta receptors, the relative count of T gamma delta to alpha beta-expressing cells is close to the peripheral count (e.g.5%), and lower than that previously observed in the synovial fluid. Interestingly, the peripheral type V gamma 9-J gamma P rearrangement using the T gamma delta cell subset was relatively decreased in the synovial membrane, as compared to synovial fluid and peripheral blood, suggesting that the T gamma delta distribution in the rheumatoid synovium resembles a thymic-like situation.

  12. Effects of RWJ 67657, a p38 mitogen activated protein kinase (MAPK) inhibitor, on the production of inflammatory mediators by rheumatoid synovial fibroblasts

    NARCIS (Netherlands)

    Westra, J; Limburg, PC; de Boer, Peter; van Rijswijk, Martin

    2004-01-01

    Objective: To investigate the effect of the p38 mitogen activated protein kinase ( MAPK) inhibitor RWJ 67657 on inflammatory mediator production by rheumatoid synovial fibroblasts (RSF). Methods: RSF were pretreated with RWJ 67657 and stimulated with TNFalpha and/or IL-1beta. Protein levels and mRNA

  13. Transcriptional network profile on synovial fluid T cells in psoriatic arthritis.

    Science.gov (United States)

    Fiocco, Ugo; Martini, Veronica; Accordi, Benedetta; Caso, Francesco; Costa, Luisa; Oliviero, Francesca; Scanu, Anna; Facco, Monica; Boso, Daniele; Gatto, Mariele; Felicetti, Mara; Frallonardo, Paola; Ramonda, Roberta; Piva, Lucia; Zambello, Renato; Agostini, Carlo; Scarpa, Raffaele; Basso, Giuseppe; Semenzato, Gianpietro; Dayer, Jean-Michel; Punzi, Leonardo; Doria, Andrea

    2015-09-01

    The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orphan receptor gamma T (RORγt)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1β, IL-2, IL-6, IL-21 and interferon (INF)-γ were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4(+)CD25(-), CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg, and either mean fluorescence intensity (MFI) of FOXP3(+) on CD4(+) Treg or MFI of classic IL-6 receptor (IL-6R) α expression on CD4(+)CD25(-) helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-γ were not detectable, whereas IL-6 and IL-1β levels were higher than in SF of non-inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORγt proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg cells and brighter MFI of IL-6Rα were observed both on CD4(+)CD25(high)- and CD4(+)CD25(-) T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1β and γC cytokines in the polarization and plasticity of Th17 and Treg cells

  14. Clinical response, pharmacokinetics, development of human anti-chimaeric antibodies, and synovial tissue response to rituximab treatment in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    R.M. Thurlings; O. Teng; K. Vos; D.M. Gerlag; L. Aarden; S.O. Stapel; J.M. van Laar; P.P. Tak; G.J. Wolbink

    2010-01-01

    Objectives: To analyse whether persistence of synovial B lineage cells and lack of clinical response to rituximab treatment in patients with rheumatoid arthritis (RA) are associated with low rituximab serum levels and anti-rituximab antibody (ARA) formation. Methods: Fifty-eight patients with RA wer

  15. Folate receptor beta as a potential delivery route for novel folate antagonists to macrophages in the synovial tissue of rheumatoid arthritis patients

    NARCIS (Netherlands)

    J.W. van der Heijden; R. Oerlemans; B.A.C. Dijkmans; H. Qi; C.J. van der Laken; W.F. Lems; A.L. Jackman; M.C. Kraan; P.P. Tak; M. Ratnam; G. Jansen

    2009-01-01

    OBJECTIVE: To determine the expression of folate receptor beta (FRbeta) in synovial biopsy tissues and peripheral blood lymphocytes from rheumatoid arthritis (RA) patients and to identify novel folate antagonists that are more selective in the targeting and internalization of FRbeta than methotrexat

  16. Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment

    NARCIS (Netherlands)

    A.W.R. van Kuijk; P. Reinders-Blankert; T.J.M. Smeets; B.A.C. Dijkmans; P.P. Tak

    2006-01-01

    Background: The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis ( PsA). Identification of proinflammatory molecules in the synovium may help to identify potentially therapeutic targets. Objective: To investigate extensively the features of cell i

  17. A prospective, randomised, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: effects of adalimumab treatment on synovial tissue

    NARCIS (Netherlands)

    A.W.R. van Kuijk; D.M. Gerlag; K. Vos; G. Wolbink; M. de Groot; M.A. de Rie; A.H. Zwinderman; B.A.C. Dijkmans; P.P. Tak

    2009-01-01

    OBJECTIVE: To determine which of the changes in synovial tissue correlates best with clinical response associated with effective therapy (adalimumab) to facilitate the planning of future studies with therapeutic agents for psoriatic arthritis (PsA). METHODS: A total of 24 patients with active PsA we

  18. Dickkopf‑related protein 1 induces angiogenesis by upregulating vascular endothelial growth factor in the synovial fibroblasts of patients with temporomandibular joint disorders.

    Science.gov (United States)

    Jiang, Sheng-Jun; Li, Wei; Li, Ying-Jie; Fang, Wei; Long, Xing

    2015-10-01

    Angiogenesis has an important role in the progression of temporomandibular joint disorders (TMD). The aim of the present study was to explore the association between dickkopf‑related protein 1 (DKK‑1) and angiogenesis in TMD. The expression levels of DKK‑1 and vascular endothelial growth factor (VEGF) were quantified by an ELISA assay of the synovial fluid from patients with TMD. The correlation between DKK‑1 and VEGF was analyzed by Pearson correlation test. Synovial fibroblasts were isolated from patients with TMD and were subsequently treated with recombinant human DKK‑1, anti‑DKK‑1 antibody, hypoxia inducible factor‑1α (HIF‑1α), or small interfering RNA (siRNA). The expression levels of DKK‑1, HIF‑1α, and VEGF were subsequently quantified. The present study also investigated the effects of DKK‑1 on the migration of human umbilical vein endothelial cells (HUVEC). Increased expression levels of DKK‑1 were concordant with increased expression levels of VEGF in the synovial fluid from patients with TMD. In the synovial fibroblasts, DKK‑1 increased the expression levels of VEGF, and promoted HIF‑1α nuclear localization. In addition, DKK‑1 induced HUVEC migration, and HIF‑1α siRNA inhibited DKK‑1‑induced cell migration. The results of the present study indicate that DKK‑1 is associated with angiogenesis in the synovial fluid of patients with TMD. Furthermore, HIF‑1α may be associated with DKK‑1‑induced HUVEC activation.

  19. Interleukin-35 (IL-35) inhibits proliferation and promotes apoptosis of fibroblast-like synoviocytes isolated from mice with collagen-induced arthritis.

    Science.gov (United States)

    Li, Yunxia; Wu, Suqin; Li, Yuxuan; Jiang, Shenyi; Lin, Tiantian; Xia, Liping; Shen, Hui; Lu, Jing

    2016-09-01

    Rheumatoid arthritis (RA) is an inflammatory disorder of the joints that affects 0.5-1 % of adults. Excessive growth of the fibroblast-like synoviocytes (FLS) promotes hyperplasia of synovial tissues and causes its invasion into the bone and cartilage, which eventually causes deformity and dysfunction of affected joints. Interleukin 35 (IL-35) was shown to suppress the inflammatory responses to collagen-induced arthritis (CIA) via upregulation of T regulatory cells and suppression of T helper type 17 cells in a mouse model. To study the effects of IL-35 on the proliferation and apoptosis frequency of cultured FLS isolated from mice with CIA as well as to examine the effects of IL-35 on CIA in vivo. Thirty DBA/1 J mice, which are used as an animal model for RA, were divided randomly (ten mice per group) to a CIA group (collagen treatment), a CIA + IL-35 group (collagen and IL-35 treatments), and a control group (no treatment). Starting on the 24th day after collagen administration, IL-35 was injected intraperitoneally into mice of the CIA + IL-35 group once per day for 10 days. An arthritis index was calculated, and pathological analysis of synovial tissue was performed. FLS isolated from CIA mice were treated with various concentrations of IL-35 (12.5-100 ng/ml). The MTT assay was used to examine FLS proliferation, and apoptosis frequency of FLS was detected by flow cytometry. On day 24, the CIA mice began to exhibit arthritis symptoms, and the symptoms rapidly progressed with time. Treatment with IL-35 significantly alleviated arthritis symptoms and reduced the synovial tissue inflammation. In addition, IL-35 treatment inhibited proliferation and promoted apoptosis in cultured FLS from CIA mice in a dose-dependent manner. IL-35 could ameliorate the symptoms of arthritis in the CIA mouse model in vivo and inhibited FLS proliferation while promoting FLS apoptosis in vitro, thereby exhibited the potential in inhibiting the progression of RA.

  20. Interleukin-21 Induces Proliferation and Proinflammatory Cytokine Profile of Fibroblast-like Synoviocytes of Patients with Rheumatoid Arthritis.

    Science.gov (United States)

    Xing, R; Yang, L; Jin, Y; Sun, L; Li, C; Li, Z; Zhao, J; Liu, X

    2016-01-01

    Fibroblast-like synoviocytes (FLS) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) through aggressive proliferation and invasion, and certain proinflammatory cytokines may affect synoviocyte proliferation. To evaluate whether interleukin-21 (IL-21) could promote proliferation and proinflammatory cytokine production by RA-FLS, immunohistochemistry and immunoblotting were performed to observe the expression of IL-21 receptor (IL-21R) in synovial tissues and FLS from RA and osteoarthritis (OA) patients. The MTS assay was used to analyse RA-FLS proliferation. The concentrations of IL-6 and tumour necrosis factor-α (TNF-α) in culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). The signalling pathways triggered by IL-21 were characterized by immunoblotting. IL-21R was upregulated in the synovial tissues and FLS of RA patients as compared with OA patients. IL-21 stimulated RA-FLS proliferation and promoted the production of TNF-α and IL-6 and blockade of IL-21/IL-21R pathway with IL-21R.Fc attenuated IL-21-induced proliferation and secretion of TNF-α and IL-6. Moreover, IL-21 induced activation of the ERK1/2, PI3K/AKT and STAT3 pathways, and blockade of these pathways attenuated IL-21-induced proliferation and secretion of TNF-α and IL-6. These results suggest that IL-21 could promote RA-FLS proliferation and production of proinflammatory cytokines. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of RA.

  1. In vitro synthesis of prostaglandin E2 by synovial tissue after helium-neon laser radiation in rheumatoid arthritis.

    Science.gov (United States)

    Barberis, G; Gamron, S; Acevedo, G; Cadile, I; Juri, H; Campana, V; Castel, A; Onetti, C M; Palma, J A

    1996-08-01

    This paper reports the effect of helium-neon laser radiation (power of 5 mW and 632.8 nm wave length) on the synthesis of PGE2 in vitro in synovial tissue of biopsy samples of knee joints in patients with chronic rheumatoid arthritis stages II or III. Twelve patients were studied. Each patient received 15 applications of He-Ne laser. Eleven points for He-Ne laser applications were selected in one of the affected knees. The energy density used was 8 J/cm2 per application point. The He-Ne laser therapy reduced the synthesis of PGE2. The analysis of the data revealed a statistically significant difference between the levels of the synthesis of PGE2 before treatment (17.69 +/- 2.65 ng mg-1 of dry tissue h-1) and after treatment (13.85 +/- 2.73 ng mg-1 of dry tissue h-1), with p < 0.01 comparing mean values. This was also accompanied by relief of pain (91.6%), and a favorable subjective report from the patient. We conclude that PGE2 is a quantifiable parameter that could explain what causes pain relief in patients with rheumatoid arthritis that are treated with He-Ne laser.

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

    DEFF Research Database (Denmark)

    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...

  3. Histone Deacetylase Inhibitors Suppress Inflammatory Activation of Rheumatoid Arthritis Patient Synovial Macrophages and Tissue

    NARCIS (Netherlands)

    A.M. Grabiec; S. Krausz; W. de Jager; T. Burakowski; D. de Groot; M.E. Sanders; B.J. Prakken; W. Maslinski; E. Eldering; P.P. Tak; K.A. Reedquist

    2010-01-01

    Macrophages contribute significantly to the pathology of many chronic inflammatory diseases, including rheumatoid arthritis (RA), asthma, and chronic obstructive pulmonary disease. Macrophage activation and survival are tightly regulated by reversible acetylation and deacetylation of histones, trans

  4. Bmx regulates LPS-induced IL-6 and VEGF production via mRNA stability in rheumatoid synovial fibroblasts.

    Science.gov (United States)

    Palmer, Christine D; Mutch, Brenda E; Page, Theresa H; Horwood, Nicole J; Foxwell, Brian M J

    2008-06-13

    Discordant cytokine production is characteristic of chronic inflammatory conditions like rheumatoid arthritis (RA), and anti-cytokine therapeutics are becoming routinely used to treat RA in the clinic. Fibroblasts from rheumatoid synovium have been shown to contribute to cytokine production in inflamed joints; likewise these cells also produce cytokines in response to inflammatory mediators signalling through Toll like receptors (TLRs). Tyrosine kinase activity is essential to LPS-induced cytokine production, and we have previously implicated a role for the Tec kinase, Bmx, in inflammatory cytokine production. Here we show that Bmx kinase activity in RASF is increased following LPS stimulation and that Bmx is involved in the regulation of LPS-induced IL-6 and VEGF production via mRNA stabilisation. This is an important insight into the regulation of VEGF, which is involved in a wide range of different pathologies, and may lead to more effective design of novel anti-inflammatory/angiogenic therapeutics for conditions such as RA.

  5. Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis

    NARCIS (Netherlands)

    Kruithof, E; Baeten, D; De Rycke, L; Vandooren, B; Foell, D; Roth, J; Canete, JD; Boots, AM; Veys, EM; De Keyser, F

    2005-01-01

    At present only few biological data are available to indicate whether psoriatic arthritis (PsA) is part of the spondyloarthropathy (SpA) concept, whether it is a separate disease entity or a heterogeneous disease group with oligoarticular/ axial forms belonging to SpA and polyarticular forms resembl

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

    Energy Technology Data Exchange (ETDEWEB)

    Kubassova, Olga, E-mail: olga@imageanalysis.org.u [Image Analysis Ltd., The Waterfront, Old Mill Lane, Saltaire BD17 7EZ (United Kingdom); Boesen, Mikael, E-mail: parker@frh.regionh.d [Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Frederiksberg, Copenhagen (Denmark); Cimmino, Marco A., E-mail: cimmino@unige.i [Clinica Reumatologica, DI.M.I., Universita di Genova, Viale Benedetto XV, 6, 16129 Genova (Italy); Bliddal, Henning [Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Frederiksberg, Copenhagen (Denmark)

    2010-06-15

    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.

  7. Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: possible factors contributing to persistence of organisms.

    Science.gov (United States)

    Nanagara, R; Duray, P H; Schumacher, H R

    1996-10-01

    To perform the first systematic electronmicroscopic (EM) and immunoelectron microscopy (IEM) study of the pathological changes and the evidence of spirochete presence in synovial membranes and synovial fluid (SF) cells of patients with chronic Lyme arthritis. EM examination was performed on four synovial membrane and eight SF cell samples from eight patients with chronic Lyme disease. Spirochetal antigens in the samples were sought by IEM using monoclonal antibody to Borrelia burgdorferi outer surface protein A (OspA) as the immunoprobe. Prominent ultrastructural findings were surface fibrin-like material, thickened synovial lining cell layer and signs of vascular injury. Borrelia-like structures were identified in all four synovial membranes and in two of eight SF cell samples. The presence of spirochetal antigens was confirmed by IEM in all four samples studied (one synovial membrane and three SF cell samples). OspA labelling was in perivascular areas, deep synovial stroma among collagen bundles, and in vacuoles of fibroblasts in synovial membranes; and in cytophagosomes of mononuclear cells in SF cell samples. Electron microscopy adds further evidence for persistence of spirochetal antigens in the joint in chronic Lyme disease. Locations of spirochetes or spirochetal antigens both intracellulary and extracellulary in deep synovial connective tissue as reported here suggest sites at which spirochaetes may elude host immune response and antibiotic treatment.

  8. 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

  9. Lactate and T{sub 2} measurements of synovial aspirates at 1.5 T: differentiation of septic from non-septic arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Wiener, Edzard; Zanetti, Marco; Hodler, Juerg; Pfirrmann, Christian W.A. [Orthopedic University Hospital Balgrist, Department of Radiology, Zurich (Switzerland)

    2008-08-15

    The aim of this study was to differentiate septic from non-septic arthritis by measuring lactate concentration with {sup 1}H magnetic resonance spectroscopy (HMRS) and by estimating total protein content with the assessment of T{sub 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{sub 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 < 0.001 and <0.01, respectively). Measured lactate concentrations and T{sub 2} relaxation times (as an indicator of total protein content) were moderately correlated to laboratory-confirmed lactate concentration (r{sup 2}=0.71) and total protein content (r{sup 2}=0.73). Markedly increased lactate concentrations (>6 mmol/L) in combination with low T{sub 2} values (<550 ms) identify septic arthritis with a sensitivity of 70% and a specificity of 89%. Spectroscopic measurements of lactate concentration in combination with the estimation of protein content using T{sub 2} may be of value in the differentiation of septic from non-septic arthritis. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Damasio, Maria Beatrice [G. Gaslini Institute, Department of Diagnostic Imaging, Genoa (Italy); Malattia, Clara [G. Gaslini Institute, Department of Pediatrics 2, Genoa (Italy); Martini, Alberto [University of Genova, Department of Pediatrics, Genoa (Italy); Toma, Paolo [Bambin Gesu Pediatric Hospital, Rome (Italy)

    2010-06-15

    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.)

  11. Synovial visualization during Tc-99m MDP bone scanning in septic arthritis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Yon, J.W. Jr.; Spicer, K.M.; Gordon, L.

    1983-06-01

    During Tc-99m medronate (MDP) bone scintigraphy, visualization of the synovium during blood flow and blood pool phases was present in a patient with septic arthritis of the left knee. Inflammation with hyperemia of the synovium was the cause for radionuclide localization, which was enhanced by the large photon-deficient effusion distending the suprapatellar bursa. The synovium was not seen on delayed images after redistribution of the radionuclide from blood pool to bone phase.

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

    DEFF Research Database (Denmark)

    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......) = 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...

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Londei, M.; Savill, C.M.; Verhoef, A.; Brennan, F.; Leech, Z.A.; Feldmann, M. (Charing Cross Sunley Research Centre, London (England)); Duance, V. (Bristol Laboratory (England)); Maini, R.N. (Kennedy Institute of Rheumatology, London (England))

    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.

  15. Quercetin promotes the apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis by upregulating lncRNA MALAT1.

    Science.gov (United States)

    Pan, Fang; Zhu, Lihua; Lv, Haozhe; Pei, Chunpeng

    2016-11-01

    Rheumatoid arthritis (RA) is a chronic autoimmune joint disease and fibroblast-like synoviocytes (FLS) are the resident mesenchymal cells of synovial joints. Quercetin is a dietary antioxidant. In this study, we aimed to explore the mechanisms responsible for the quercetin-induced apoptosis of FLS from patients with RA (termed RAFLS). RAFLS viability was determined following treatent of the cells with or without quercetin using the Cell Counting kit-8 (CCK-8) assay. The apoptosis of the RAFLS was analyzed using the Annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit I. The results revealed that RAFLS viability decreased and apoptosis increased in following treatment with quercetin. The differentially expressed long non-coding RNAs (lncRNAs) were screened and marked by PCR array following treatment with quercetin. The expression levels of the screened lncRNAs were then determined and compared in the cells treated with or without quercetin by quantitative PCR. The lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was finally selected. Small interfering RNA (siRNA) was then used to knock down the expression of MALAT1 in order to determine the role of MALAT1 in the quercetin-induced apoptosis of RAFLS. The results revealed that the knockdown of MALAT1 inhibited RAFLS apoptosis. At the same time, the expression of caspase-3 and caspase-9 was significantly decreased in the cells in which MALAT1 was knocked down. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was activated; this activation is known to be associated with enhanced cell proliferation and decreased apoptosis. The findings of our study indicate that quercetin promotes RAFLS apoptosis by upregulating lncRNA MALAT1, and that MALAT1 induces apoptosis by inhibiting the activation of the PI3K/AKT pathway.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Chondrogenic differentiation of human subchondral progenitor cells is affected by synovial fluid from donors with osteoarthritis or rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Krüger Jan

    2012-03-01

    Full Text Available Abstract Background Microfracture is a first-line treatment option for cartilage repair. In microfracture, subchondral mesenchymal cortico-spongious progenitor cells (CSP enter the defect and form cartilage repair tissue. The aim of our study was to investigate the effects of joint disease conditions on the in vitro chondrogenesis of human CSP. Methods CSP were harvested from the subchondral bone marrow. CSP characterization was performed by analysis of cell surface antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic differentiation potential, histologically. To assess the effect of synovial fluid (SF on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy (ND, osteoarthritis (OA and rheumatoid arthritis donors (RA without transforming growth factor beta 3. Results CSP showed the typical cell surface antigen pattern known from mesenchymal stem cells and were capable of osteogenic, adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF, histological staining as well as gene expression analysis of typical chondrogenic marker genes showed that SF from ND and OA induced the chondrogenic marker genes aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP and link protein, compared to controls not treated with SF. In contrast, the supplementation with SF from RA donors decreased the expression of aggrecan, type II collagen, COMP and link protein, compared to CSP treated with SF from ND or OA. Conclusion These results suggest that in RA, SF may impair cartilage repair by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may has no negative, but a delaying effect on the cartilage matrix formation.

  18. Regulation of metalloproteinases and NF-kappaB activation in rabbit synovial fibroblasts via E prostaglandins and Erk: contrasting effects of nabumetone and 6MNA.

    Science.gov (United States)

    Pillinger, Michael H; Dinsell, Victoria; Apsel, Beth; Tolani, Sonia N; Marjanovic, Nada; Chan, Edwin S L; Gomez, Paul; Clancy, Robert; Chang, Lih-Fan; Abramson, Steven B

    2004-07-01

    1 Nabumetone is a prodrug that is converted in vivo into 6-methoxy-2-naphthylacetic acid (6MNA), a cyclooxygenase inhibitor with anti-inflammatory properties. We tested the effects of nabumetone and 6MNA on the inflammatory responses of synovial fibroblasts (SFs). 2 Brief exposures to 6MNA (50-150 microm) had no effect on IL-1beta/TNF-alpha (each 20 ng ml(-1))-stimulated Erk activation. Longer exposures depleted prostaglandin E1 (PGE1) as much as 70%, and stimulated Erk as much as 300%. Nabumetone (150 microm) inhibited Erk activation by 60-80%. 6MNA (50-150 microm) stimulated (approximately 200%) and nabumetone (150 microm) inhibited (approximately 50%) matrix metalloproteinase (MMP)-1, but not MMP-13 secretion from SFs. 3 6MNA stimulation of MMP-1 secretion was inhibited approximately 30% by PGE1 (1 microm) and approximately 80% by the Erk pathway inhibitor UO126 (10 microm), confirming that PGE depletion and Erk activation mediate MMP-1 secretion by 6MNA. 4 Consistent with its role as an Erk inhibitor, nabumetone (150 microm) abrogated 6MNA enhancement of MMP-1 secretion. 5 UO126 (10 microm) and nabumetone (150 microm) inhibited (approximately 70 and 40%, respectively), but 6MNA (150 microm) enhanced (approximately 40%), NF-kappaB activation. 6 Our data indicate that 6MNA shares with other COX inhibitors several proinflammatory effects on synovial fibroblasts. In contrast, nabumetone demonstrates anti-inflammatory and potentially arthroprotective effects that have not been previously appreciated.

  19. Sea urchin puncture resulting in PIP joint synovial arthritis: case report and MRI study.

    Science.gov (United States)

    Liram, N; Gomori, M; Perouansky, M

    2000-01-01

    Of the 600 species of sea urchins, approximately 80 may be venomous to humans. The long spined or black sea urchin, Diadema setosum may cause damage by the breaking off of its brittle spines after they penetrate the skin. Synovitis followed by arthritis may be an unusual but apparently not a rare sequel to such injury, when implantation occurs near a joint. In this case report, osseous changes were not seen by plain x-rays. Magnetic resonance imaging (MRI) was used to expose the more salient features of both soft tissue and bone changes of black sea urchin puncture injury 30 months after penetration. In all likelihood, this type of injury may be more common than the existing literature at present suggests. It is believed to be the first reported case in this part of the world as well as the first MRI study describing this type of joint pathology. Local and systemic reactions to puncture injuries from sea urchin spines have been described previously. These may range from mild, local irritation lasting a few days to granuloma formation, infection and on occasions systemic illness. The sea urchin spines are composed of calcium carbonate with proteinaceous covering. The covering tends to cause immune reactions of variable presentation. There are only a handful of reported cases with sea urchin stings on record, none of them from the Red Sea. However, this condition is probably more common than is thought and can present difficulty in diagnosis. In this case report, the inflammation responded well to heat treatment, mobilization and manipulation of the joint in its post acute and chronic stages. As some subtle changes in soft tissues and the changes in bone were not seen either on plain x-rays or ultrasound scan, gadolinium-enhanced MRI was used to unveil the marked changes in the joint.

  20. Competitive coordination of Cu2+ between cysteine and pyrophosphate ion: toward sensitive and selective sensing of pyrophosphate ion in synovial fluid of arthritis patients.

    Science.gov (United States)

    Deng, Jingjing; Yu, Ping; Yang, Lifen; Mao, Lanqun

    2013-02-19

    Direct selective and sensitive sensing of pyrophosphate ion (PPi) in synovial fluid of arthritis patients is of great importance because of its crucial roles in the diagnosis and therapy of arthritic diseases. In this study, we demonstrate a sensitive and selective method for PPi sensing in synovial fluid of arthritis patients with gold nanoparticles (Au-NPs) as the signal readout based on the competitive coordination chemistry of Cu(2+) between cysteine and PPi. Initially, Au-NPs stabilized with cysteine are red in color and exhibit absorption at 519 nm in the UV-vis spectrum. The addition of an aqueous solution of Cu(2+) to the Au-NPs dispersion containing cysteine causes the aggregation of Au-NPs, resulting in the wine red-to-blue color change and the appearance of a new absorption at 650 nm in the UV-vis spectrum of the Au-NPs dispersion. The subsequent addition of PPi to the Au-NPs aggregation well solubilizes the aggregated Au-NPs with the changes in both the color and the UV-vis spectrum of the Au-NPs dispersion. These changes are ascribed to the higher coordination reactivity between Cu(2+) and PPi than that between Cu(2+) and cysteine. On the basis of this, the concentration of PPi can be visualized with the naked eyes through the blue-to-wine red color change of the Au-NPs dispersion and quantitatively determined by UV-vis spectroscopy. Under the optimized conditions, the ratio of the absorbance at 650 nm (A(650)) to that at 519 nm (A(519)) shows a linear relationship with PPi concentration within a concentration range from 130 nM to 1.3 mM. The method demonstrated here is highly sensitive, free from the interference from other species in the synovial fluid, and is thus particularly useful for fast and simple clinic diagnosis of arthritic diseases.

  1. Dominant and shared T cell receptor beta chain variable regions of T cells inducing synovial hyperplasia in rheumatoid arthritis.

    Science.gov (United States)

    Mima, T; Ohshima, S; Sasai, M; Nishioka, K; Shimizu, M; Murata, N; Yasunami, R; Matsuno, H; Suemura, M; Kishimoto, T; Saeki, Y

    1999-09-16

    Previously, we demonstrated the presence of at least two distinct subpopulations of patients with rheumatoid arthritis (RA) employing a cell-transfer experiment using severe combined immunodeficient (SCID) mice. One group of patients, whose T cells derived from the rheumatoid joints, induced synovial hyperplasia (SH) in the SCID mice (the positive group). The other group did not display the induction of SH (the negative group). TCR/Vbeta gene usage analysis indicated that some dominant T cell subpopulations were oligoclonally expanding only in the rheumatoid joints, and not in the periphery of the patients of the positive group. Moreover, these T cell subpopulations were not seen in the joints of patients in the negative group or in non-RA patients. In addition, the preferential uses of certain TCR/Vbetas (Vbeta8, Vbeta12, Vbeta13, and Vbeta14) genes were demonstrated in these T cells. In this study, to investigate whether these T cells are driven by a certain antigen(s), the third complementarity determining regions (CDR3s) of TCR/Vbeta, especially Vbeta8 and Vbeta14 PCR products, were cloned and sequenced. As a result, a dominant CDR3 sequence, CASS-PRERAT-YEQ, was found in Vbeta14+ T cells from the rheumatoid joint of a patient (Patient 1) of the positive group with a Vbeta14 skew. The identical CDR3 sequence also predominated in Vbeta14+ T cells from the rheumatoid joint of another patient (Patient 7) of the positive group with a Vbeta14 skew. In addition, in the patients (Patients 4, 7, 8) of the positive group with a Vbeta8 skew, other dominant CDR3 sequences, CASS-ENS-YEQ and CASS-LTEP-DTQ, were found as in the case of Vbeta14. However, no identical CDR3 sequences were detected dominantly in the joints of the patients in the negative group or in non-RA patients. A Vbeta14+ T cell clone (TCL), named G3, with the identical CDR3 sequence, CASS-PRERAT-YEQ, was isolated successfully from Patient 1, and cell transfer of G3 with autologous irradiated peripheral

  2. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint

    Directory of Open Access Journals (Sweden)

    K. Okamoto

    2015-02-01

    Full Text Available Several epidemiological studies have reported that temporomandibular disorders (TMDs are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular joint (TMJ is made up of connective tissue with an extracellular matrix (ECM composed of collagen and proteoglycan. One proteoglycan family, comprised of small leucine-rich repeat proteoglycans (SLRPs, was found to be involved in collagen fibril formation and interaction. In recent years, the participation of SLRPs such as lumican and fibromodulin in the internal derangement of TMJ has been suggested. Although these SLRPs may contribute to the restoration of the synovium, their effect is still unclear. The purpose of this study was to investigate the effect of DHEA, a sex hormone, on the expression of lumican and fibromodulin in human temporomandibular specimens and in cultured human TMJ fibroblast-like synovial cells in the presence or absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta. In the in vivo study, both normal and osteoarthritic (OA human temporomandibular synovial tissues were immunohistochemically examined. In the in vitro study, five fibroblast-like synoviocyte (FLS cell lines were established from human TMJ synovial tissue of patients with osteoarthritis. The subcultured cells were then incubated for 3, 6, 12 or 24 h with/without IL-1beta (1 ng/mL in the presence or absence of DHEA (10 μM. The gene expression of lumican and fibromodulin was examined using the real-time polymerase chain reaction (PCR and their protein expression was examined using immunofluorescent staining. We demonstrated that the expression of lumican

  3. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint.

    Science.gov (United States)

    Okamoto, K; Kiga, N; Shinohara, Y; Tojyo, I; Fujita, S

    2015-02-23

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular joint (TMJ) is made up of connective tissue with an extracellular matrix (ECM) composed of collagen and proteoglycan. One proteoglycan family, comprised of small leucine-rich repeat proteoglycans (SLRPs), was found to be involved in collagen fibril formation and interaction. In recent years, the participation of SLRPs such as lumican and fibromodulin in the internal derangement of TMJ has been suggested. Although these SLRPs may contribute to the restoration of the synovium, their effect is still unclear. The purpose of this study was to investigate the effect of DHEA, a sex hormone, on the expression of lumican and fibromodulin in human temporomandibular specimens and in cultured human TMJ fibroblast-like synovial cells in the presence or absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). In the in vivo study, both normal and osteoarthritic (OA) human temporomandibular synovial tissues were immunohistochemically examined. In the in vitro study, five fibroblast-like synoviocyte (FLS) cell lines were established from human TMJ synovial tissue of patients with osteoarthritis. The subcultured cells were then incubated for 3, 6, 12 or 24 h with/without IL-1beta (1 ng/mL) in the presence or absence of DHEA (10 μM). The gene expression of lumican and fibromodulin was examined using the real-time polymerase chain reaction (PCR) and their protein expression was examined using immunofluorescent staining. We demonstrated that the expression of lumican significantly

  4. 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

  5. Synergistic effects of ethanol and isopentenyl pyrophosphate on expansion of γδ T cells in synovial fluid from patients with arthritis.

    Directory of Open Access Journals (Sweden)

    Agneta J Laurent

    Full Text Available Low to moderate ethanol consumption has been associated with protective effects in autoimmune diseases such as rheumatoid arthritis, RA. An expansion of γδ T cells induced by isopentenyl pyrophosphate, IPP, likewise seems to have a protective role in arthritis. The aim of this project was to test the hypothesis that low doses of ethanol can enhance IPP-induced expansion of synovial fluid γδ T cells from patients with arthritis and may thereby potentially account for the beneficial effects of ethanol on symptoms of the arthritic process. Thus, mononuclear cells from synovial fluid (SF from 15 patients with arthritis and from peripheral blood (PB from 15 healthy donors were stimulated with low concentrations of ethanol and IPP for 7 days in vitro. IPP in combination with ethanol 0.015%, 2.5 mM, equivalent to the decrease per hour in blood ethanol concentration due to metabolism, gave a significantly higher fractional expansion of SF γδ T cells compared with IPP alone after 7 days (ratio 10.1+/-4.0, p<0.0008, n = 12 in patients with arthritis. Similar results were obtained for PB γδ T cells from healthy controls (ratio 2.0+/-0.4, p<0.011, n = 15. The augmented expansion of γδ T cells in SF is explained by a higher proliferation (p = 0.0034, n = 11 and an increased survival (p<0.005, n = 11 in SF cultures stimulated with IPP plus ethanol compared to IPP alone. The synergistic effects of IPP and ethanol indicate a possible allosteric effect of ethanol. Similar effects could be seen when stimulating PB with ethanol in presence of risedronate, which has the ability to increase endogenous levels of IPP. We conclude that expansion of γδ T cells by combinatorial drug effects, possibly in fixed-dose combination, FDC, of ethanol in the presence of IPP might give a protective role in diseases such as arthritis.

  6. MR findings of synovial disease in children and young adults: Part 2

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee K.; Zbojniewicz, Andrew M.; Merrow, Arnold C.; Emery, Kathleen H. [Cincinnati Children' s Medical Center, Department of Radiology, Cincinnati, OH (United States); Cheon, Jung-Eun; Kim, In-One [Seoul National University Children' s Hospital, Department of Radiology, Seoul (Korea, Republic of)

    2011-04-15

    Synovium is the thin membranous lining of a joint. It produces synovial fluid, which lubricates and nourishes the cartilage and bone in the joint capsule. Synovial diseases in children can be classified as normal structures as potential sources of pathology (synovial folds: plicae, infrapatellar fat pad clefts), noninfectious synovial proliferation (juvenile idiopathic arthritis, hemophilic arthropathy, lipoma arborescens, synovial osteochondromatosis, pigmented villonodular synovitis, reactive synovitis), infectious synovial proliferation (pyogenic arthritis, tuberculous arthritis), deposition disease (gouty arthropathy), vascular malformation, malignancy (metastasis) and intra-/periarticular cysts and cyst-like structures. Other intra-articular neoplasms, such as intra-articular synovial sarcoma, can mimic synovial disease in children. (orig.)

  7. Inhibition of microRNA-21 decreases the invasiveness of fibroblast-like synoviocytes in rheumatoid arthritis via TGFβ/Smads signaling pathway

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    Gaoxin Xiong

    2016-07-01

    Full Text Available Objective(s: MicroRNA-21 (miR21 is aberrantly elevated in rheumatoid arthritis (RA patients, the significance of this microRNA in RA pathogenesis and treatment, however, has not been investigated. In this study, by using RA-derived fibroblast-like synoviocyte (FLS cells as a model, we investigated the effect and corresponding mechanism of miR21 inhibition on FLSs invasion. Materials and Methods:miR21 expression in synovial tissue and FLSs in RA patients and non-RA controls were determined by stem-loop RT-PCR. The effect of miR21 on FLSs viability and invasiveness were evaluated using miR21 inhibition. Cell viability was evaluated by MTT assay and the expression of genes at mRNA and protein levels was determined by RT-PCR and Western blot, respectively. Results: Our results showed that miR21 expression was highly increased in synovial tissue and FLSs in RA patients. Also, we reported that miR21 inhibitor treatment could significantly suppress the invasiveness of FLSs without affecting cell viability. The decreased FLSs invasion by miR21 inhibition was associated with down-regulated expression of matrix metalloproteinase (MMP-1, MMP3, and MMP13. Further analysis revealed that miR21 inhibition could suppress the expression of TGFβ1 and Smad4, but promote that of Smad7. Moreover, suppression of FLS invasion and MMPs expression by miR21 treatment could be counteracted by additional TGFβ1 treatment. Conclusion:Our results indicated that miR21 inhibition can down-regulate the expression of MMP1, MMP3, and MMP13 and consequently suppress the invasiveness of FLS, which is achieved through TGFβ1/Smad4/7 signaling pathway. The findings of this study could offer a novel approach for RA treatment.

  8. 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.

  9. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    LENUS (Irish Health Repository)

    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.

  11. Progression of Mycoplasma hyosynoviae infection in three pig herds. Development of tonsillar carrier state, arthritis and antibodies in serum and synovial fluid in pigs from birth to slaughter

    DEFF Research Database (Denmark)

    Hagedorn-Olsen, T.; Nielsen, N.C.; Friis, N.F.

    1999-01-01

    In this investigation, natural infection with Mycoplasma hyosynoviae was followed in groups of individual pigs in three different herds with regard to occurrence of tonsillar carrier state, clinical arthritis and development of antibodies in serum and in synovial fluid. Antibodies were detected...... by a polyclonal enzyme-linked immunosorbent assay (ELISA) developed for experimental use. The infection with M hyosynoviae progressed very differently in the three herds investigated. In one herd, the infection was apparently limited to adult Figs. In a second herd, all pigs became tonsillar carriers of M...... in some, but not all, pigs. In all three herds, M. hyosynoviae infection was carried in the tonsils of the adult pigs, but it was only occasionally transmitted from sows to piglets. Maternal antibodies were transferred to the piglets and persisted for approximately 8-12 weeks. After weaning, some pigs...

  12. 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.

  13. Evaluation of a balloon constant rate infusion system for treatment of septic arthritis, septic tenosynovitis, and contaminated synovial wounds: 23 cases (2002-2005).

    Science.gov (United States)

    Meagher, Daniel T; Latimer, Federico G; Sutter, W Wes; Saville, William J A

    2006-06-15

    OBJECTIVE-To determine clinical findings and outcome in horses treated by means of a balloon constant rate infusion system. DESIGN-Retrospective case series. ANIMALS-23 horses. PROCEDURES-Medical records of horses examined at The Ohio State University veterinary teaching hospital from 2002 to 2005 that had septic arthritis, septic tenosynovitis, or penetration of a synovial structure and in which treatment involved a balloon constant rate infusion system were searched. Information pertaining to signalment, history, physical examination findings, clinicopathologic data, treatment, and duration of hospitalization was recorded. RESULTS-Mean+/- SD duration of hospitalization was 11.5+/-5.26 days. No correlation between duration of clinical signs and duration of hospitalization or duration of infusion pump use was detected, but correlations between WBC count and duration of hospitalization and WBC and duration of infusion-pump use were observed. All horses survived to discharge. Follow-up information was obtained on 17 horses, 16 of which were alive at the time of follow-up. Twelve of 13 horses for which followup information was available for at least 5 months were alive 5 months or longer after discharge. Thirteen of the 16 horses alive at follow-up were reported by owners as not lame, whereas the remaining 3 were mildly lame or intermittently moderately lame or had developed angular limb deformity in the contralateral limb. CONCLUSIONS AND CLINICAL RELEVANCE-Balloon constant rate infusion systems may be used effectively in treatment of septic arthritis, septic tenosynovitis, and contaminated synovial wounds. Clinical response and long-term outcome appeared to be comparable to results obtained with other techniques.

  14. Endomorphins in rheumatoid arthritis, osteoarthritis, and experimental arthritis.

    Science.gov (United States)

    Jessop, David S; Fassold, Alexander; Wolff, Christine; Hofbauer, Rafael; Chover-Gonzalez, Antonio; Richards, Louise J; Straub, Rainer H

    2010-04-01

    The opioid tetrapeptides endomorphins (EM)-1 and EM-2 are widely expressed in central nervous system and immune tissues of rats and humans. Their analgesic properties are well characterized but they also have anti-inflammatory properties. EM-1 significantly attenuated the onset of hindpaw inflammation in adjuvant-induced arthritis in rats. Immunohistochemical staining demonstrated the presence of EMs in T cells, macrophages, and fibroblasts in synovial tissues from patients with osteo- or rheumatoid arthritis (RA). In an ex vivo superfusion system, EM-1 potently inhibited the release of proinflammatory cytokines interleukin (IL)-6 and IL-8 from synovial tissues from patients with osteo- or RA. These results demonstrate that EMs are endogenously synthesized within human immune cells and have the potential to act as potent therapeutic agents in the treatment of chronic inflammatory disease. We discuss the clinical potential for EM analogues chemically modified to resist proteolytic degradation and identify modified protease-resistant analogues with enhanced bioactivity.

  15. Synovial biopsy

    Science.gov (United States)

    Biopsy - synovial membrane ... fluid in and out of the area. A biopsy grasper is inserted through the trocar and turned ... Synovial biopsy helps diagnose gout and bacterial infections, or rule out other infections. It can be used to diagnose ...

  16. 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.

  17. Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model

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    Boechat AL

    2015-10-01

    Full Text Available Antônio Luiz Boechat,1,2,* Catiúscia Padilha de Oliveira,3,* Andrea Monteiro Tarragô,2 Allyson Guimarães da Costa,2 Adriana Malheiro,1,2 Silvia Stanisçuaski Guterres,3 Adriana Raffin Pohlmann3,41Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal do Amazonas, Manaus, 2Programa de Pós-Graduação e Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, 3Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, 4Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil*These authors contributed equally to this workBackground: Rheumatoid arthritis (RA is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX. Despite the importance of this drug in RA, 8%–16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules.Objective: The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution.Methods: Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA and the effect on edema formation, TNF-a levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments

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

    Directory of Open Access Journals (Sweden)

    Olga N Karpus

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  19. 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...

  20. Expression of discoidin domain receptor 2 (DDR2) extracellular domain in pichia pastoris and functional analysis in synovial fibroblasts and NIT3T3 cells.

    Science.gov (United States)

    Zhang, Wei; Ding, Tianbing; Zhang, Jian; Su, Jin; Li, Fuyang; Liu, Xinping; Ma, Wenyu; Yao, Libo

    2006-10-01

    Discoidin domain receptor 2 (DDR2) is a kind of protein tyrosine kinases associated with cell proliferation and tumor metastasis, and collagen, identified as a ligand for DDR2, up-regulates matrix metallloproteinase 1 (MMP-1) and MMP-2 expression in cellular matrix. To investigate the roles of DDR2 in destruction of cartilage in rheumatoid arthritis (RA) and tumor metastasis, we tried to express extracellular domain of DDR2 fused with a His tag to increase protein solubility and facilitate purification (without signal peptide and transmembrane domain, designated DR) in Pichia pastoris, purify the expressed protein, and characterize its function, for purpose of future application as a specific DDR2 antagonist. Two clones of relative high expression of His-DR were obtained. After purification by a Ni-NTA (nitric-tri-acetic acid) chromatographic column, soluble fused His-DR over 90% purity were obtained. Competitive binding inhibition assay demonstrated that expressed His-DR could block the binding of DDR2 and natural DDR2 receptors on NIT3T3 and synovial cell surfaces. Results of RT-PCR, Western blotting, and gelatinase zymography showed that His-DR was capable of inhibiting MMP-1 and MMP-2 secretion from NIT3T3 cells and RA synoviocytes stimulated by collagen II. For MMP-1, the inhibitory effect was displayed at the levels of mRNA and protein, whereas for MMP-2 it was demonstrated at the level of protein physiological activity. All these findings suggested that the fused expressed His-DR inhibited the activity of natural DDR2, and relevant MMP-1 and MMP-2 expression in synoviocytes and NIH3T3 cells provoked by collagen II.

  1. TL1A increased IL-6 production on fibroblast-like synoviocytes by preferentially activating TNF receptor 2 in rheumatoid arthritis.

    Science.gov (United States)

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

    2016-07-01

    TNF-like protein 1A (TL1A), a member of tumor necrosis factor family, recognized as a ligand of death receptor 3 (DR3) and decoy receptor 3 (DcR3). The interaction of TL1A and DR3 may participate in the pathogenesis of some autoimmune diseases including rheumatoid arthritis (RA). Our previous results showed that high concentrations of TL1A could be found in synovial and serum in RA patients, and it was correlated with disease severity. In addition, TL1A could promote Th17 differentiation induced by TGF-β and IL-6 and increased the production of IL-17A. In the present study, we found that TL1A could promote the expression of IL-6 on fibroblast-like synoviocytes (FLS) of RA patients via NF-κB and JNK signaling pathway. TL1A-stimulated FLS increased the percentage of Th17 of peripheral blood mononuclear cells (PBMC) in RA via the production of IL-6, a critical cytokine involved in the differentiation of Th17. Moreover, the blocking of tumor necrosis factor receptor 2 (TNFR2) decreased TL1A-stimulated IL-6 production by RA FLS. Our results suggest that TL1A was capable of acting on RA FLS to elevate IL-6 expression, which promoted the production of Th17. More importantly, we showed that TL1A could influence RA FLS through binding to TNFR2 rather than DR3 on FLS, which indicated that the treatment of TNF inhibitors not only blocked the TNF but also suppressed the TL1A in RA patients.

  2. Evaluation of a real-time PCR assay for simultaneous detection of Kingella kingae and Staphylococcus aureus from synovial fluid in suspected septic arthritis.

    Science.gov (United States)

    Haldar, Malay; Butler, Meghan; Quinn, Criziel D; Stratton, Charles W; Tang, Yi-Wei; Burnham, Carey-Ann D

    2014-07-01

    Direct plating of synovial fluid (SF) on agar-based media often fails to identify pathogens in septic arthritis (SA). We developed a PCR assay for the simultaneous detection of Kingella kingae and Staphylococcus aureus from SF to evaluate molecular detection in SF and to estimate the incidence of K. kingae in SA in North America. The assay was based on detection of the cpn60 gene of K. kingae and the spa gene of S. aureus in multiplex real-time PCR. K. kingae was identified in 50% of patients between 0 and 5 yr of age (n=6) but not in any patients >18 yr old (n=105). Direct plating of SF on agar-based media failed to detect K. kingae in all samples. The PCR assay was inferior to the culture-based method for S. aureus, detecting only 50% of culture-positive cases. Our findings suggest that K. kingae is a common pathogen in pediatric SA in North America, in agreement with previous reports from Europe. PCR-based assays for the detection of K. kingae may be considered in children with SA, especially in those with a high degree of clinical suspicion.

  3. Sonographic findings of the synovial fluid

    Directory of Open Access Journals (Sweden)

    W. Grassi

    2011-09-01

    Full Text Available Objective: The aim of this pictorial essay was to evaluate the sonographic features of synovial fluid in patients with arthritis. Methods: Sixty-nine patients with active synovitis (rheumatoid arthritis, psoriatic arthritis, osteoarthritis, septic arthritis, crystal arthropathies, post-traumatic arthritis were studied. Sonographic evaluation was performed with a AU-5 Harmonic, Esaote Biomedica (Genoa, Italy equipped with a 10-14 MHz broadband linear transducer and a Diasus Dynamic Imaging Ltd.(Livingston, Scotland UK equipped with a 8-16 MHz broadband linear transducer. Results: Six main different sonographic patterns were detected: 1 Anechoic: increased amount of homogeneous anechoic synovial fluid (exudative synovitis. 2 Cloudy: ecogenic structures (proteinaceous material. 3 Mixed: anechoic synovial fluid and proteinaceus material. 4 “Snow-storm” aspect: multiple mildly and heterogeneous echoic spots (9 out of 10 patients with acute gouty synovitis. 5 Dotted: multiple sparkling hyperechoic dots without posterior acoustic shadow (10 out of 12 patient with chondrocalcinosis. 6 Granular: irregular turbid aspect of the synovial fluid. It was present in 3 patient with septic arthritis. Conclusions: The results of this study indicate that high resolution ultrasonography is able to detect different features of synovial fluid. Further studies are needed to assess both sensitivity and specificity of ultrasonography in “in vivo” synovial fluid examination.

  4. Inhibition of inflammatory arthritis using fullerene nanomaterials.

    Directory of Open Access Journals (Sweden)

    Anthony L Dellinger

    Full Text Available Inflammatory arthritis (e.g. rheumatoid arthritis; RA is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC. Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis.

  5. Inhibition of inflammatory arthritis using fullerene nanomaterials.

    Science.gov (United States)

    Dellinger, Anthony L; Cunin, Pierre; Lee, David; Kung, Andrew L; Brooks, D Bradford; Zhou, Zhiguo; Nigrovic, Peter A; Kepley, Christopher L

    2015-01-01

    Inflammatory arthritis (e.g. rheumatoid arthritis; RA) is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC). Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA) were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA) in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis.

  6. Endocytosed 2-Microglobulin Amyloid Fibrils Induce Necrosis and Apoptosis of Rabbit Synovial Fibroblasts by Disrupting Endosomal/Lysosomal Membranes: A Novel Mechanism on the Cytotoxicity of Amyloid Fibrils.

    Directory of Open Access Journals (Sweden)

    Tadakazu Okoshi

    Full Text Available Dialysis-related amyloidosis is a major complication in long-term hemodialysis patients. In dialysis-related amyloidosis, β2-microglobulin (β2-m amyloid fibrils deposit in the osteoarticular tissue, leading to carpal tunnel syndrome and destructive arthropathy with cystic bone lesions, but the mechanism by which these amyloid fibrils destruct bone and joint tissue is not fully understood. In this study, we assessed the cytotoxic effect of β2-m amyloid fibrils on the cultured rabbit synovial fibroblasts. Under light microscopy, the cells treated with amyloid fibrils exhibited both necrotic and apoptotic changes, while the cells treated with β2-m monomers and vehicle buffer exhibited no morphological changes. As compared to β2-m monomers and vehicle buffer, β2-m amyloid fibrils significantly reduced cellular viability as measured by the lactate dehydrogenase release assay and the 3-(4,5-di-methylthiazol-2-yl-2,5-diphenyltetrazolium bromide reduction assay and significantly increased the percentage of apoptotic cells as measured by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. β2-m amyloid fibrils added to the medium adhered to cell surfaces, but did not disrupt artificial plasma membranes as measured by the liposome dye release assay. Interestingly, when the cells were incubated with amyloid fibrils for several hours, many endosomes/lysosomes filled with amyloid fibrils were observed under confocal laser microscopy and electron microscopy, Moreover, some endosomal/lysosomal membranes were disrupted by intravesicular fibrils, leading to the leakage of the fibrils into the cytosol and adjacent to mitochondria. Inhibition of actin-dependent endocytosis by cytochalasin D attenuated the toxicity of amyloid fibrils. These results suggest that endocytosed β2-m amyloid fibrils induce necrosis and apoptosis by disrupting endosomal/lysosomal membranes, and this novel mechanism on the cytotoxicity of amyloid

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

    DEFF Research Database (Denmark)

    Kubassove, Olga; Boesen, Mikael; Cimmino, Marco A;

    2009-01-01

    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...

  8. 类风湿关节炎和骨关节炎滑膜滑液中MMP-2和MMP-9的比较%Comparison of the MMP-2 and MMP-9 in the Knee Joint Synovial Fluid and Synovial Membrane in Patients with active Rheumatoid Arthritis and Osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    刘荣清; 林佳静; 孙伯坚; 李海波; 宋婷阁; 韩梅

    2013-01-01

    目的 检测基质金属蛋白酶-2(matrix metalloproteinases-2,MMP-2)和基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)在类风湿关节炎活动期(rheumatoid arthritis,RA)和骨关节炎(osteoarthritis,OA)活动期膝关节滑液及滑膜中的含量,并探讨两者在RA和OA病变中的作用.方法 收集宁夏医科大学总医院风湿免疫科和骨科确诊的14例RA活动期患者和24例OA活动期患者的膝关节滑液和滑膜组织,用酶联免疫吸附实验(ELISA)检测滑液中MMP-2和MMP-9的含量,用免疫组化法检测滑膜组织中MMP-9的相对表达量,组间比较采用秩和检验.结果 RA活动期患者膝关节滑液中的MMP-2和MMP-9浓度明显高于骨关节炎活动期患者(P<0.01);RA活动期患者膝关节滑膜中MMP-9的相对表达量明显高于OA活动期患者(P<0.01).结论 MMP-2和MMP-9在RA活动期患者滑液中高表达,MMP-9在RA活动期患者滑膜中高表达,可能参与RA发生发展过程中滑膜炎、骨质破坏.%Objective To compare matrix metalloproteinases - 2 ( MMP - 2) and matrix metalloproteinases - 9 ( MMP - 9) in knee joint synovial fluid and synovial membrane in patients with active rheumatoid arthritis ( RA) and active osteoarthritis ( OA) , and to explore the effects of MMP -2 and MMP -9 on lesion of RA and OA. Methods Knee joint synovial fluid and synovial membrane were collected from 14 and 24 patients with final diagnosis of RA and OA, and underwent surgery at the General Hospital of Ningxia Medical University. MMP - 2 and MMP - 9 in the synovial fluid were measured by enzyme linked immunosorbent assay (ELISA). The distributions of MMP - 9 in the synovial membrane were analyzed using immunohistochemistry. Student's t - test was used for intergroup comparison. Results The level of MMP - 2 and MMP - 9 in synovial fluid of active RA was significantly higher than that of active OA(P <0. 01) ; the relative expression of MMP -9 in synovial membrane was stronger in active RA

  9. MR findings of synovial disease in children and young adults: Part 1

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Kyung; Zbojniewicz, Andrew M.; Merrow, Arnold C.; Emery, Kathleen H. [Cincinnati Children' s Medical Center, Department of Radiology, Cincinnati, OH (United States); Cheon, Jung-Eun; Kim, In-One [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of)

    2011-04-15

    Synovial diseases in children can be classified into normal structures as potential sources of pathology (synovial folds: plicae, infrapatellar fat pad clefts); noninfectious synovial proliferation (juvenile idiopathic arthritis, hemophilic arthropathy, lipoma arborescens, synovial osteochondromatosis, pigmented villonodular synovitis, reactive synovitis), and infectious synovial proliferation, deposition disease, vascular malformations, malignancy (including metastasis) and intra-articular/periarticular cysts and cyst-like structures (ganglia). Familiarity with characteristic MR imaging findings of synovial diseases in children and young adults will enable a more confident diagnosis for earlier intervention and directed therapy. The first part of this paper will cover potential pathology of normal synovial structures as well as noninfectious synovial proliferation. (orig.)

  10. Usefulness of anti-cyclic citrullinate peptide antibody determination in synovial fluid analysis of patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    G. Valesini

    2011-09-01

    Full Text Available Objective: To assess the role of anti-cyclic citrullinated peptide (CCP antibody detection in synovial fluid (SF of RA patients compared to OA patients. Methods: We evaluated in 25 RA subjects and 14 OA patients, presenting a knee-joint effusion, the main clinical and laboratory parameters including the number of painful and/or swollen joints, Ritchie index, morning stiffness, ESR, CRP and analysis of SF obtained by therapeutic arthrocentesis. IgG anti-CCP (ELISA, rheumatoid factor (RF and total IgG (nephelometry method were measured in SF and paired serum samples. Results: We found anti-CCP antibodies and RF in 64% (16/25 and 60% (15/25 of RA sera, respectively; 72% (18/25 of RA patients were positive for anti-CCP antibodies or RF. We found a higher SF/serum ratio for anti-CCP (p<0.004 compared to that for total IgG. The calculation of anti-CCP concentration as IgG anti-CCP (units/total IgG (g L-1 revealed higher values in SF than in serum (p<0.046 in RA patients. Among these, correlation analysis showed that anti-CCP/total IgG values in SF correlated with the relative concentration of serum anti-CCP/total IgG (rs=0.842; p<0.00001 and serum anti-CCP antibody levels (rs=0.799; p<0.0001. We did not find any correlation between SF anti-CCP levels and the main characteristics of SF as well as the clinical or laboratory parameters. Conclusion: Our study give evidence for a preferential production of anti-CCP antibodies at RA joint level, confirming the pathogenetic role of these autoantibodies. Moreover, SF determination of anti-CCP, corrected for the total amount of the corresponding immunoglobulin, may be helpful as diagnostic tool in selected cases.

  11. Magnetic resonance imaging in the assessment of synovial inflammation of the hindfoot in patients with rheumatoid arthritis and other polyarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Maillefert, Jean Francis E-mail: jean-francis.maillefert@chu-dijon.fr; Dardel, Pascal; Cherasse, Anne; Mistrih, Rami; Krause, Denis; Tavernier, Christian

    2003-07-01

    Objectives: To describe the localisation of synovitis and tenosynovitis of the hindfoot observed on magnetic resonance imaging (MRI) in patients with chronic polyarthritis, and to correlate the findings of physical examination and MRI. Methods: Patients with chronic polyarthritis, and one or two painful hindfoot were included. On physical examination and on MRI, the tibio-talar, talo-calcaneal, and talo-navicular and calcaneo-cuboidal joints were adjudged to have or not synovitis, and the tibialis anterior and posterior, the peroneus longus and brevis, the flector digitorum and hallucis longus tendons to have or not tenosynovitis. Criteria for synovitis and tenosynovitis were a high signal intensity on T2-weighted images, a low signal intensity on T1-weighted images, and enhancement after Gd-DTPA injection, in the joint area, and around the tendon, respectively. The correlation between the findings of physical examination and those of MRI were evaluated using the Kappa statistics. Results: 12 patients (three men, nine women, mean age of 55.5 years{+-}11.4 S.D.) with chronic polyarthritis (rheumatoid arthritis (RA): nine, ankylosing spondylitis: one; psoriatic arthritis: one, unclassified: one) were included. All presented with one (7 patients) or two (5 patients) painful hindfeet (and swelling for 16 out of 17 hindfeet). On physical examination, 25 joints and eight tendons were adjudged to have synovitis and tenosynovitis. MRI showed synovitis in 12 out of 25 of these joints (48%), and tenosynovotis in three out of eight of these tendons (37.5%). Moreover, MRI showed ten and seven clinically unsuspected synovitis and tenosynovitis, respectively. The proportion of agreements between physical examination and MRI were 54.9% (kappa=0.1) and 88.2% (kappa=0.27) for synovitis and tenosynovitis, respectively. Conclusion: A weak correlation was observed between the findings of physical examination and MRI in patients with chronic polyarthritis and a painful hindfoot. MRI

  12. CD45RA-Foxp3(low) non-regulatory T cells in the CCR7-CD45RA-CD27+CD28+ effector memory subset are increased in synovial fluid from patients with rheumatoid arthritis.

    Science.gov (United States)

    Matsuki, Fumichika; Saegusa, Jun; Nishimura, Keisuke; Miura, Yasushi; Kurosaka, Masahiro; Kumagai, Shunichi; Morinobu, Akio

    2014-07-01

    Increased numbers of regulatory T (Treg) cells are found in synovial fluid from patients with rheumatoid arthritis (RASF) compared with peripheral blood. However, Treg cells in RASF have been shown to have a decreased capacity to suppress T cells. Here we phenotypically classified CD4+ T cells in RASF into six subsets based on the expression of CD45RA, CCR7, CD27 and CD28, and demonstrated that the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in synovial fluid compared with peripheral blood. In addition, the proportion of Foxp3+ Treg cells in the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in RASF. Furthermore, most of the Foxp3+ Treg cells in RASF were non-suppressive CD45RA-Foxp3(low) non-Treg cells, and the frequency of the non-Treg cells in the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in RASF. Our findings suggest that the pro-inflammatory environment in RA joints may induce the increase of CD45RA-Foxp3(low) non-Treg cells in synovial fluid.

  13. Water-soluble fullerene (c60 inhibits the development of arthritis in the rat model of arthritis

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    Kazuo Yudoh

    2009-10-01

    Full Text Available Kazuo Yudoh1, Rie Karasawa1, Kayo Masuko2, Tomohiro Kato2 1Institute of Medical Science, 2Department of Biochemistry, St. Marianna University School of Medicine, Kawasaki, JapanAbstract: Recently, it has been demonstrated that oxygen free radicals have an important role as a signaling messenger in the development of inflammation and osteoclastogenesis, suggesting the implication of oxygen free radicals in the pathogenesis of arthritis. The aim of this study was to examine the potential of a strong free-radical scavenger, water-soluble fullerene (C60, as a protective agent against synovitis in arthritis, both in vitro and in vivo. In the presence or absence of C60 (0.1, 1.0, 10.0 µM, human synovial fibroblasts, synovial infiltrating lymphocytes or macrophages were incubated with tumor necrosis factor-α (TNF-α (10.0 ng/mL, and the production of proinflammatory cytokines by the individual cells were analyzed. C60 significantly suppressed the TNF-α-induced production of proinflammatory cytokines in synovial fibroblasts, synovial infiltrating lymphocytes and macrophages in vitro. Adjuvant induced arthritic rats were used as an animal model of arthritis. Rats were divided into two subgroups: control and treatment with C60 at 10.0 µM. The left ankle joint was injected intraarticularly with water-soluble C60 (20 µl in the C60-treated group, while, as a control, the left ankle joint in the control rats received phosphate-buffered saline (20 µl, once weekly for eight weeks. Ankle joint tissues were prepared for histological analysis. In adjuvant-induced arthritic rats, intra-articular treatment with C60 in vivo reduced synovitis and alleviated bone resorption and destruction in the joints, while control ankle joints showed progression of synovitis and joint destruction with time. These findings indicate that C60 is a potential therapeutic agent for inhibition of arthritis.Keywords: fullerene, inflammation, arthritis, synovitis, bone resorption

  14. 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.

  15. Evaluation of the degree of clinical rheumatoid arthritis activity based on the concentrations of cytokines TNF-alpha, IL-12, IL-15, and IL-18 in serum and synovial fluid

    Directory of Open Access Journals (Sweden)

    Petrović-Rackov Ljiljana

    2006-01-01

    Full Text Available Bacground/Aim. Experimental in vitro and in vivo investigations in a mouse model have proved that TNF-alpha, IL-12, IL- 15 and IL-18 participate in the pathogenesis of erosive inflammatory arthritis. The aim of this research was to determine the clinical significance of cytokines in the evaluation of the activity of rheumatoid arthritis (RA. Methods. Inside a 4-year period we followed-up 64 patients with RA as newly occurred or in the phase of worsening. We observed the clinical manifestation of the disease upon wluch we divided the patients in to 3 groups: the patients with low active RA, patients with moderate active RA, and the patients with wild active RA. The control group (n = 25 patients included the patients with osteoarthrosis (OA, and arthritis of the knee. In the samples of serum of all of the patients the concentrating of cytokines TNF-alpha, IL-12, IL-15, and IL-18 were determined using the immunoenzymatic methods in mice for human interleukines. By comparing the concentrations in 30 patients with the high, 14 patients with moderate, and 20 patients with the mild activity of RA it was determined that the patients with the high degree of the disease activity, had significantly high (p < 0.01; p < 0.05 concentrations of the examined cytokines in blood and synovial fluid as compared to the patients with the moderate and mild active disease. There was a relationship (p < 0.01 between the concentrations of cytokines in blood and synovial fluid with the quantity of the Disease Activity Score in 28 joints. Conclusions. Cytokines concentrations could be good indicators of the degree of the general activity of RA. This research could contribute to the interpretation of insufficiently well known views of the pathogenesis role and significance of citokines in an active disease.

  16. Effect of Interleukin-1beta and Dehydroepiandrosterone on the Expression of Lumican and Fibromodulin in Fibroblast-Like Synovial Cells of the Human Temporomandibular Joint

    OpenAIRE

    Okamoto, K; Kiga, N.; Shinohara, Y.; Tojyo, I.; Fujita, S.

    2015-01-01

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular jo...

  17. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint

    OpenAIRE

    Okamoto, K; Kiga, N.; Shinohara, Y.; Tojyo, I.; Fujita, S.

    2015-01-01

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular jo...

  18. 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 ...

  19. 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...... treatment. The synovial membrane volume was significantly reduced (median -52%) in all 9 patients brought into clinical remission (p

  20. Human monocyte elastolytic activity, the propeptides of types I and III procollagen, proteoglycans, and interleukin-6 in synovial fluid from patients with arthritis

    DEFF Research Database (Denmark)

    Jensen, H S; Jensen, L T; Saxne, T;

    1991-01-01

    elastolytic activity, using the levels of synovial fluid interleukin-6 and serum C reactive protein as additional markers of cell activation. Proteoglycan levels were measured as an indication of cartilage degradation and the types I and III procollagen propeptides as markers of synovial membrane turnover. We...... found that elastolysis by live M phi and the levels of interleukin-6 and C reactive protein correlated significantly with proteoglycan concentrations but not with the procollagen propeptides. These findings suggest that human M phi elastolytic activation is a biologically relevant factor in cartilage...

  1. 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 psoriatic...

  2. Apoptosis as a target for gene therapy in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Gabriel Adrián Rabinovich

    2000-01-01

    Full Text Available Rheumatoid arthritis (RA is characterized by chronic inflammation of the synovial joints resulting from hyperplasia of synovial fibroblasts and infiltration of lymphocytes, macrophages and plasma cells, all of which manifest signs of activation. All these cells proliferate abnormally, invade bone and cartilage, produce an elevated amount of pro-inflammatory cytokines, metalloproteinases and trigger osteoclast formation and activation. Some of the pathophysiological consequences of the disease may be explained by the inadequate apoptosis, which may promote the survival of autoreactive T cells, macrophages or synovial fibroblasts. Although RA does not result from single genetic mutations, elucidation of the molecular mechanisms implicated in joint destruction has revealed novel targets for gene therapy. Gene transfer strategies include inhibition of pro-inflammatory cytokines, blockade of cartilage-degrading metalloproteinases, inhibition of synovial cell activation and manipulation of the Th1-Th2 cytokine balance. Recent findings have iluminated the idea that induction of apoptosis in the rheumatoid joint can be also used to gain therapeutic advantage in the disease. In the present review we will discuss different strategies used for gene transfer in RA and chronic inflammation. Particularly, we will highlight the importance of programmed cell death as a novel target for gene therapy using endogenous biological mediators, such as galectin-1, a beta-galactoside-binding protein that induces apoptosis of activated T cells and immature thymocytes.

  3. Arthritis

    Science.gov (United States)

    ... injected into painful joints or given by mouth. Disease-modifying anti-rheumatic drugs (DMARDs) are used to treat autoimmune arthritis. They include methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide. ...

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

    Science.gov (United States)

    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.

  5. Synergistic effects of ethanol and isopentenyl pyrophosphate on expansion of γδ T cells in synovial fluid from patients with arthritis

    DEFF Research Database (Denmark)

    Laurent, Agneta J; Bindslev, Niels; Johansson, Björn;

    2014-01-01

    Low to moderate ethanol consumption has been associated with protective effects in autoimmune diseases such as rheumatoid arthritis, RA. An expansion of γδ T cells induced by isopentenyl pyrophosphate, IPP, likewise seems to have a protective role in arthritis. The aim of this project was to test...... with ethanol in presence of risedronate, which has the ability to increase endogenous levels of IPP. We conclude that expansion of γδ T cells by combinatorial drug effects, possibly in fixed-dose combination, FDC, of ethanol in the presence of IPP might give a protective role in diseases such as arthritis....

  6. Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  7. Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Zhijun Jiao

    2012-01-01

    Full Text Available It has been reported that Notch family proteins are expressed in synovium tissue and involved in the proliferation of synoviocyte from rheumatoid arthritis (RA. The aim of this paper was to investigate whether Notch signaling mediated TNF-α-induced cytokine production of cultured fibroblast-like synoviocytes (FLSs from RA. Exposure of RA FLSs to TNF-α (10 ng/ml led to increase of Hes-1, a target gene of Notch signaling, and a marked upregulation of Notch 2, Delta-like 1, and Delta-like 3 mRNA levels. Blockage of Notch signaling by a γ-secretase inhibitor (DAPT inhibited IL-6 secretion of RA FLSs in response to TNF-α while treatment with recombinant fusion protein of Notch ligand Delta-like 1 promoted such response. TNF-α stimulation also induced IL-6 secretion in OA FLSs; however, the Hes-1 level remained unaffected. Our data confirm the functional involvement of Notch pathway in the pathophysiology of RA FLSs which may provide a new target for RA therapy.

  8. Smoothened Regulates Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Activation of Rho GTPase Signaling

    Science.gov (United States)

    Peng, Wei-xiang; Zhu, Shang-ling; Zhang, Bai-yu; Shi, Yi-ming; Feng, Xiao-xue; Liu, Fang; Huang, Jian-lin; Zheng, Song Guo

    2017-01-01

    Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P < 0.05). However, treatment with KAAD-cyclopamine or transfection with Smo-siRNA suppressed migration of RA-FLSs and showed an inhibitory effect of Rho GTPase signaling. Together, these results suggest that Smo plays an important role in RA-FLSs migration through activation of Rho GTPase signaling and may contribute to progression of RA, thus, targeting Shh signal may have a therapeutic potential in patients with RA. PMID:28261216

  9. Gastrodia elata attenuates inflammatory response by inhibiting the NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes.

    Science.gov (United States)

    Li, Yu; Wang, Li-Min; Xu, Jian-Zhong; Tian, Ke; Gu, Chen-Xi; Li, Zhi-Fu

    2017-01-01

    Gastrodia elata (GE), which belongs to the Orchidaceae family, was found to possess anti-inflammatory activity. However, the effect of GE on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) remains largely unknown. Thus, the aim of this study was to investigate the effects of GE on tumor necrosis factor-α (TNF-α)-induced inflammatory response in RA-FLS and the underlying molecular mechanism was also explored. Our results demonstrated that GE significantly attenuated TNF-α-induced IL-6 and IL-8 production in RA-FLS. GE also inhibited TNF-α-induced MMP-3 and MMP-13 expression in RA-FLS. Furthermore, pretreatment with GE significantly attenuated TNF-α-induced the expression of p-p65 and IκBα degradation in RA-FLS. In conclusion, this study demonstrated for the first time that GE attenuated inflammatory response by inhibiting the NF-κB pathway signaling in RA-FLS. Thus, GE might have a therapeutic potential towards the treatment of RA.

  10. The Mechanisms Underlying Chronic Inflammation in Rheumatoid Arthritis from the Perspective of the Epigenetic Landscape

    Directory of Open Access Journals (Sweden)

    Yasuto Araki

    2016-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory autoimmune disease that is characterized by synovial hyperplasia and progressive joint destruction. The activation of RA synovial fibroblasts (SFs, also called fibroblast-like synoviocytes (FLS, contributes significantly to perpetuation of the disease. Genetic and environmental factors have been reported to be involved in the etiology of RA but are insufficient to explain it. In recent years, accumulating results have shown the potential role of epigenetic mechanisms, including histone modifications, DNA methylation, and microRNAs, in the development of RA. Epigenetic mechanisms regulate chromatin state and gene transcription without any change in DNA sequence, resulting in the alteration of phenotypes in several cell types, especially RASFs. Epigenetic changes possibly provide RASFs with an activated phenotype. In this paper, we review the roles of epigenetic mechanisms relevant for the progression of RA.

  11. Effect of TLR4/MyD88 Signaling Pathway on Expression of IL-1β and TNF-α in Synovial Fibroblasts from Temporomandibular Joint Exposed to Lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Xuefen Lin

    2015-01-01

    Full Text Available Accumulating evidence from previous studies suggested that interleukin-1 (IL-1β and tumor necrosis factor-α (TNF-α play an important role in pathogenesis of temporomandibular disorders (TMD. However, the cell surface receptors and the intracellular signal pathways leading to these cytokines expression are not fully understood. In the current study, we investigated the roles of Toll-like receptor 4 (TLR4 and its adaptor myeloid differentiation factor 88 (MyD88 in the expression of IL-1β and TNF-α in synovial fibroblasts (SFs separated from rat temporomandibular joint (TMJ with lipopolysaccharide (LPS stimulation. The results showed that treatment with LPS could increase TLR4, MyD88, IL-1β, and TNF-α expression at both mRNA and protein levels. In addition, increased expression of IL-1β and TNF-α could be blocked by treatment with TAK-242, a blocker of TLR4 signaling, and also by MyD88 inhibitory peptide (MIP. These findings suggested that maybe TLR4/MyD88 signal transduction pathway participates in enhanced expression of IL-1 and TNF-α in patients with TMD. The activation of TLR4/MyD88 signal transduction pathway which results in production of proinflammatory factors may play a role in the pathogenesis of TMD.

  12. 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.

  13. TNFR1 and TNFR2 differentially mediate TNF-α-induced inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes.

    Science.gov (United States)

    Zhang, Hongfeng; Xiao, Weiguo

    2017-04-01

    TNF-α has long been implicated in the progression of rheumatoid arthritis (RA). However, how the receptors of TNF-α, namely TNFR1 and TNFR2, mediate TNF-α-induced inflammatory responses in fibroblast-like synoviocytes (FLS) in RA has not been elucidated. In the present study, primary FLS cells were isolated from RA patients and treated with TNF-α in vitro. The exogenous TNF-α induced the expression and release of endogenous TNF-α in FLS. In addition, TNF-α led to gradual downregulation of TNFR1 following 1 h treatment. By contrast, the expression of TNFR2 was markedly upregulated after 12 h treatment with TNF-α. Moreover, following TNF-α treatment, the expression of interleukin (IL)-2, IL-6, and IL-8 was gradually increased with time, but their mRNA levels dropped significantly at 48 h. We further investigated the differential functions of TNFR1 and TNFR2 in FLS by conducting siRNA-mediated knockdown. The TNF-α autocrine was inhibited to a greater extent in TNFR1-silenced FLS compared with TNFR2-silenced FLS. Silencing of TNFR1, not TNFR2, activated intrinsic apoptosis and inhibited TNF-α-induced cytokine production in FLS. These results suggest that TNFR1 is the major pro-inflammatory mediator of TNF-α in FLS, whereas TNFR2, which is upregulated in response to prolonged TNF-α stimulation, may act as an immunosuppressor in FLS for the prevention of overwhelming inflammatory reactions.

  14. Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis.

    Science.gov (United States)

    Kehlen, A; Thiele, K; Riemann, D; Langner, J

    2002-03-01

    Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4+ CD45RO+ memory T cells. Overproduction of IL-17 was detected in the synovium of patients with rheumatoid arthritis (RA) compared to patients with osteoarthritis. In contrast to the restricted expression of IL-17, the IL-17 receptor (IL-17R/CDw217) is expressed ubiquitously. Using a real-time RT-PCR assay, we detected similar absolute levels of IL-17R mRNA expression in fibroblast-like synoviocytes (SFC) from patients with RA (mean 9 pg/microg total RNA; ranged from 0.1 pg to 96 pg IL-17R mRNA/microg total RNA) compared to synoviocytes of non-RA patients. Analysis of the IL-17R surface expression confirmed the results obtained for IL-17R mRNA expression. Exposure of SFC to IL-17 led to a mRNA induction of CXC chemokines IL-8, GRO-alpha and GRO-beta. An anti-IL-17 antibody blocked these effects of IL-17. The MAPK p38 appears necessary for the regulation of IL-8, GRO-alpha and GRO-beta expression as shown by inhibition with SB203580. The inhibitors genistein (tyrosine kinase inhibitor) and calphostin C (inhibitor of protein kinase C) reduced significantly the IL-17-stimulated mRNA expression of IL-8, GRO-alpha and GRO-beta in SFC, whereas PD98059 (inhibitor of MEK-1/2) was without effect. Pharmacological drugs used in therapy of RA, such as cyclosporin and methotrexate, induced a fourfold increase of IL-17R mRNA expression and augmented the IL-17-stimulated IL-8 expression. Our results support the hypothesis that IL-17/IL-17R may play a significant role in the pathogenesis of RA contributing to an unbalanced production of cytokines as well as participating in connective tissue remodelling.

  15. SYNOVIAL CELL SARCOMA

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    M. Farzan

    1997-06-01

    Full Text Available Ten cases of synovial cell sarcoma are reported. The youngest patient was a 2'A years old boy with synovial cell sarcoma of the knee and the oldest one was a man with synovial cell sarcoma of the elbow.

  16. Percentages of CD4+CD161+ and CD4−CD8−CD161+ T Cells in the Synovial Fluid Are Correlated with Disease Activity in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    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.

  17. 前列腺素E2干预后交叉韧带成纤维细胞和滑膜细胞的迁移%Effects of prostaglandin E2 on the migration of posterior cruciate ligament fibroblasts and synovial cells

    Institute of Scientific and Technical Information of China (English)

    陈荣富; 王春莉; 谢静; 黄伟; 梁熙; 宋国立; 符纯锋; 陈诚

    2012-01-01

    BACKGROUND: Cells migration is one of the important steps in the process of wound repair. But the effects of prostaglandin E2 on the migration of posterior cruciate ligament fibroblasts and synovial cells remain unclear. OBJECTIVE: To observe the effects of prostaglandin E2 on the migration of posterior cruciate ligament fibroblasts and synovial cells under mono-culture and Transwell co-culture in vitro. METHODS: Posterior cruciate ligament fibroblasts and synovial cells were mono-cultured and co-cultured by Transwell. Then the mono-cultured cells or co-cultured cells were treated by 10 ug/L prostaglandin E2. Cell growth status was observed and compared. Cell migration was assessed by wound healing assay at 24 hours after treatment. RESULTS AND CONCLUSION: The migration rates of posterior cruciate ligament fibroblasts and synovial cells under co-culture were increased by 128% and 48% compared with the mono-cultured cells. Prostaglandin E2 decreased the migration rates of the mono-cultured posterior cruciate ligament fibroblasts and synovial cells by 28% and 14% compared with the mono-culture control, and also decreased the migration rates of the co-cultured cells by 37% and 24% compared with the co-culture group. These results indicate that prostaglandin E2 inhibited the migration of both posterior cruciate ligament fibroblasts and synovial cells, especially stronger in co-cultured posterior cruciate ligament fibroblasts.%背景:细胞迁移是组织损伤后修复过程中的重要环节之一,但是膝关节交叉韧带损伤后局部产生的细胞因子前列腺素E2对后交叉韧带成纤维细胞和滑膜细胞迁移的影响尚未见报道.目的:在后交叉韧带成纤维细胞与滑膜细胞单培养和共培养的条件下,研究前列腺素E2对此2种细胞迁移的影响.方法:体外培养人后交叉韧带成纤维细胞和滑膜细胞,分别进行2种细胞的单培养和Transwell共培养,并用质量浓度10 μg/L的前列腺素E2干预.比较

  18. Equine Septic Arthritis and Serum Amyloid A

    OpenAIRE

    Ludwig, Elsa Karen

    2016-01-01

    Bacterial infection within a joint, septic arthritis, is a serious condition in horses that can lead to long-term joint disease if the infection is not resolved quickly. Equine septic arthritis is diagnosed primarily based on clinical signs and synovial fluid cytology. Septic synovial fluid is characterized by significant elevations in total protein (TP) and total nucleated cell count (TNCC). However, in some cases it can be difficult to distinguish between septic arthritis and non-septic joi...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Expression of Smoothened and its role in endothelial cells in synovial tissues of rheumatoid arthritis%类风湿关节炎滑膜血管内皮细胞中Smoothened的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    朱尚玲; 彭蔚湘; 罗敏琪; 王明霞; 林灼锋; 黄建林

    2013-01-01

    目的:初步观察Sonic Hedgehog信号通路分子Smoothened(Smo)在类风湿关节炎(rheumatoid arthritis,RA)滑膜血管内皮细胞的表达及其生物学意义.方法:收集4例病情中度活动的RA患者的滑膜组织,同时收集4例外伤或半月板损伤(无关节炎)者滑膜组织作为对照组,免疫组化检测滑膜组织Smo蛋白表达情况.采用人脐静脉内皮细胞系EA.hy926作为滑膜血管内皮细胞的模型,予不同浓度肿瘤坏死因子α(TNF-α)处理,Western blotting检测Smo蛋白表达;采用RNAi技术转染体外合成的特异性Smo-siRNA,应用Western blotting检测沉默效果;转染siRNA 24 h后,经TNF-α/放线菌素D(actinomycin D,ActD)诱导细胞凋亡,CCK-8法检测细胞存活率,流式细胞术检测细胞凋亡情况.结果:RA患者滑膜组织Smo表达高于对照组,以血管内皮细胞表达尤为明显.EA.hy926细胞经TNF-α刺激后,Smo蛋白表达上调(P<0.05).RNA干扰EA.hy926细胞Smo表达后,细胞存活率为(24.30±0.45)%,低于阴性对照组的(36.86±0.62)%(P<0.05),细胞凋亡率为(48.00±1.96)%,高于阴性对照组的(31.70±0.82)%(P<0.05).结论:Smo可能参与了RA患者滑膜组织血管内皮细胞凋亡的调控.%AIM: To investigate the expression of Sonic Hedgehog signaling pathway-associated factor Smoothened ( Smo) and its role in endothelial cells in synovial tissue of active rheumatoid arthritis ( RA) . METHODS: Smo expression in synovial tissue from 4 RA patients and 4 patients with trauma or meniscal injury ( without arthritis, used for control) was detected by the method of immunohistochemistry. Human umbilical vein endothelial cell line EA. hy926 was used as the model of synovial vascular endothelial cells. The expression of Smo was detected by Western blotting after TNF-α treatment. The small interfering RNA (siRNA) specifically targeting Smo gene was synthesized and transfected into EA. hy926 cells. The interference efficiency of the siRNA on the production of Smo

  1. Targeting the epigenetic modifications of synovial cells

    OpenAIRE

    Huber, L. C.; Jüngel, A.; Gay, S

    2009-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial tissues of joints. Like in other autoimmune-related disorders, both the etiology as well as the pathogenesis of RA has not yet been completely unravelled. It is generally accepted, though, that autoimmune disorders develop through a combination of the individual genetic susceptibility, environmental factors, and dysregulated immune responses. Genetic predisposition has been described in RA, in par...

  2. The therapeutic effect of extracellular superoxide dismutase (EC-SOD) mouse embryonic fibroblast (MEF) on collagen-induced arthritis (CIA) mice.

    Science.gov (United States)

    Yu, Dong Hoon; Kim, Myoung Ok; Kim, Sung Hyun; Shin, Mi Jung; Kim, Bong Soo; Kim, Hei Jung; Lee, Sang Ryeul; Lee, Sang Gyu; Yoo, Seung-Ah; Kim, Wan Uk; Hyun, Byung Hwa; Park, Young Sik; Kim, Tae Yoon; Ryoo, Zae Young

    2008-01-01

    Rheumatoid arthritis is a chronic inflammatory disease. The generation of reactive oxygen species (ROS) within an inflamed joint has been suggested as playing a significant pathogenic role. Extracellular superoxide dismutase (EC-SOD) is a major scavenger enzyme of ROS, which has received growing attention for its therapeutic potential. To investigate the therapeutic effect of EC-SOD in mice with collagen-induced arthritis (CIA), we used mouse embryonic fibroblast (MEF) of transgenic mice that overexpresses EC-SOD on the skin by using hK14 promoter. DBA/1 mice that had been treated with bovine type II collagen were administrated subcutaneous injections of EC-SOD transgenic MEF (each at 1.4 x 10(60 cells) on days 28, 35, and 42 after primary immunization. To test EC-SOD activity, blood samples were collected in each group on day 49. The EC-SOD activity was nearly 1.5-fold higher in the transgenic MEF-treated group than in the nontransgenic MEF-treated group (p CIA mice and this approach may be a safer and more effective form of therapy for rheumatoid arthritis.

  3. Fungal arthritis simulating juvenile rheumatoid arthritis.

    OpenAIRE

    Haapasaari, J; Essen, R V; Kahanpää, A; Kostiala, A A; Holmberg, K; Ahlqvist, J

    1982-01-01

    Petriellidium boydii is often isolated from maduromycosis but has recently been associated with arthritis. A previously healthy 6-year-old boy developed chronic purulent arthritis of the knee after a bicycle accident. Culture of aspirate grew no pathogens and antibiotic treatment had no effect. Culture of synovial fluid grew P boydii, which responded initially to amphotericin but reappeared after six months. Subsequent treatment with miconazole was stopped after development of haematuria. The...

  4. Mangiferin: A promising therapeutic agent for rheumatoid arthritis treatment.

    Science.gov (United States)

    Luczkiewicz, P; Kokotkiewicz, A; Dampc, A; Luczkiewicz, M

    2014-11-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. Despite aggressive treatment with anti-rheumatic drugs, progressive destruction of joints continues to occur in RA patients, who subsequently require joint surgery. A lot of evidence suggest that fibroblast-like synovial cells (FLS) play crucial role in joint degradation and the propagation of inflammation in RA. The expansion of fibroblast populations in the joint results primarily from the inhibition of pro-apoptotic pathways, rather than large scale proliferation. Because multiple factors, which contribute to fibroblast activation and enhance their destructive potential, are under control of transcription factor NF-κB, this pathway presents an interesting target for RA therapy. However, due to the lack of specificity, NF-κB inhibitors may exert severe side effects. Given the above, there has recently been more interest in natural substances of plant origin which are regarded as a safe alternatives for synthetic drugs. Mangiferin, the naturally occurring polyphenol with excellent anti-inflammatory and antioxidative properties, exhibits strong pro-apoptotic effect toward synoviocytes isolated from human synovia. Moreover, it shows no cytotoxicity toward cultivated chondrocytes and reduces the levels of matrix metalloproteinases. Considering that mangiferin is a natural constituent of foods and traditional herbal medicines, showing fewer adverse effects and low toxicity, we hypothesize that it may prove effective in the treatment of RA and prevention against joint destruction.

  5. The effect of isometric exercise of the hand on the synovial blood flow in patients with rheumatoid arthritis measured by color Doppler ultrasound

    DEFF Research Database (Denmark)

    Ellegaard, Karen; Torp-Pedersen, Søren; Lund, Hans;

    2013-01-01

    In 90% of patients with rheumatoid arthritis (RA), the joints of the hand are affected. Studies of grip strength training have not indicated a negative effect on disease activity after training. Introduction of ultrasound Doppler (USD) to measure increased blood flow induced by inflammation has...... made it possible to investigate the direct effect on blood supply in the synovium after training. In this case-control study, 24 patients with RA with USD activity in the wrist joint participated. The USD activity was measured by the color fraction (CF) (CF = colored pixels/total number of pixels...... in the CF was seen between the training and control groups, neither at baseline nor at follow-up (P = 0.82 and P = 0.48). Patients withdrawing from training had a significantly higher CF than the other patients (P > 0.001). The results in this study might indicate that the flow in the synovium assessed...

  6. Genetic polymorphism directs IL-6 expression in fibroblasts but not selected other cell types.

    Science.gov (United States)

    Noss, Erika H; Nguyen, Hung N; Chang, Sook Kyung; Watts, Gerald F M; Brenner, Michael B

    2015-12-01

    Interleukin (IL)-6 blockade is an effective treatment for rheumatoid arthritis (RA), and synovial fibroblasts are a major IL-6 producer in the inflamed joint. We found that human RA and osteoarthritis (OA) synovial fibroblasts derived from independent donors reproducibly segregated into low, medium, and high IL-6 producers, independent of stimulus, cell passage, or disease state. IL-6 expression pattern correlated strongly with total mRNA expression, not mRNA stability, suggesting transcriptional rather than posttranscriptional regulation. High-fibroblast IL-6 expression was significantly associated with the IL-6 proximal promoter single nucleotide polymorphism (SNP) rs1800795 minor allele (CC) genotype. In contrast, no association between this SNP and IL-6 production was detected in CD14(+) monocytes, another major producer of synovial IL-6. Luciferase expression assays confirmed that this SNP was associated with differential IL-6 expression in fibroblasts. To date, several association studies examining rs1800795 allele frequency and disease risk have reported seemingly conflicting results ranging from no association to association with either the major or minor allele across a spectrum of conditions, including cancer and autoimmune, cardiovascular, infectious, and metabolic diseases. This study points to a prominent contribution from promoter genetic variation in fibroblast IL-6 regulation, but not in other IL-6-producing cell types. We propose that some of the heterogeneity in these clinical studies likely reflects the cellular source of IL-6 in specific diseases, much of which may be produced by nonhematopoietic cells. These results highlight that functional analysis of disease-associated SNPs on gene expression and pathologic processes must consider variation in diverse cell types.

  7. Effects of the supernatant from ankylosing spondylitis synovial cells culture on the osteogenic differentiation of ligament fibroblasts%强直性脊柱炎滑膜细胞培养上清液对韧带成纤维细胞成骨分化的影响

    Institute of Scientific and Technical Information of China (English)

    徐卫东; 梁志民; 袁恒锋

    2012-01-01

    Objective To investigate the effects of synovial cells culture fluid on the differentiation of ligament fibroblasts into osteoblasts. Methods Specimens of ligament and synovium were obtained from the hip joints with ankylosing spondylitis respectively. The primary cell culture of ligament fibroblasts and synovial cells were processed and then the supernatant of synovial cells in the first passage was collected and used to induce ligament cells. Osteogenic phenotype and alkaline phosphatase (ALP) activity were determined at the days of 0, 5,10,15 and 20 respectively. Calcium deposit was detected by Von Kossa staining at the 25th day. Results With time extending, the expression of ALP and osteocalcin increased significantly at day 10 and reached a peak at day 15. Calcium deposit could be detected at day 25. Conclusions The supernatant of synovial cells cuture plays a certain role on the differentiation of ligament fibroblasts into osteoblasts.%目的 探讨强直性脊柱炎(AS)滑膜细胞培养上清液对韧带成纤维细胞成骨分化的影响.方法 分别进行AS患者滑膜和韧带成纤维细胞原代培养,收集第1代的滑膜细胞培养液上清液,应用此上清液对韧带成纤维细胞进行诱导,分别于0、5、10、15、20 d检测碱性磷酸酶和骨钙素表达水平,并于25 d时进行钙结节染色.结果 在应用AS滑膜细胞培养上清液对韧带成纤维细胞进行诱导的第10天,碱性磷酸酶(ALP)和骨钙素(OC)表达水平明显升高,并在第15天达到高峰.第25天时进行钙结节Von Kossa染色,发现有钙结节形成.结论 AS滑膜细胞培养上清液对韧带成纤维细胞具有成骨诱导分化的能力.

  8. PROBLEMS OF EPIGENOME IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    V A Kozlov

    2011-01-01

    Full Text Available Rheumatoid arthritis (RA that is a brilliant representative of the large family of autoimmune diseases remains to be, by and large, a disease that is far from being adequately investigated. This concerns the etiology and pathogenesis of the disease and effective approaches to its treatment. The review gives the data available in the literature on the role of epigenomic mechanisms regulating the functioning of genes in both immunocompetent cells and synovial fibroblasts, the major targets of autoimmune cells. The presence of a few sources of hypomethylated DNA in RA patients suggests that these molecules make a considerable contribution to the pathogenesis of the disease. Furthermore, the found hypermethylation of certain genes, besides the pathogenetic value of this phenomenon, may be used to develop new approaches to treating RA, which are based on the demethylation processes of these genes.

  9. The effect of isometric exercise of the hand on the synovial blood flow in patients with rheumatoid arthritis measured by color Doppler ultrasound.

    Science.gov (United States)

    Ellegaard, Karen; Torp-Pedersen, Søren; Lund, Hans; Pedersen, Kirsten; Henriksen, Marius; Danneskiold-Samsøe, Bente; Bliddal, Henning

    2013-01-01

    In 90% of patients with rheumatoid arthritis (RA), the joints of the hand are affected. Studies of grip strength training have not indicated a negative effect on disease activity after training. Introduction of ultrasound Doppler (USD) to measure increased blood flow induced by inflammation has made it possible to investigate the direct effect on blood supply in the synovium after training. In this case-control study, 24 patients with RA with USD activity in the wrist joint participated. The USD activity was measured by the color fraction (CF) (CF = colored pixels/total number of pixels in ROI). Twenty-four patients were assigned to an 8-week grip strength training program. At baseline and after 8 weeks of training, an USD examination of the wrist joint was performed. In the training group, we measured grip strength and pain in the wrist joint. Six patients withdrew from the training because of pain or change in medication. Eighteen patients served as control group. There was a modest, not significant, decrease in the CF in response to training (1.86%; P = 0.08). Grip strength increased 8.8% after training (P = 0.055). Pain in motion deceased after training (P = 0.04). No difference in the CF was seen between the training and control groups, neither at baseline nor at follow-up (P = 0.82 and P = 0.48). Patients withdrawing from training had a significantly higher CF than the other patients (P > 0.001). The results in this study might indicate that the flow in the synovium assessed by USD is not affected by grip strength training.

  10. A novel tumor-suppressor candidate gene-ndr2 is differentially expressed between osteoarthritis synovium cells and rheumatoid arthritis synovium fibroblasts

    Institute of Scientific and Technical Information of China (English)

    DENG Yan-chun; WANG Ji-cun; LIU Xin-ping; YAO Li-bo

    2004-01-01

    To test whether the novel tumor-suppressor candidate gene-ndr2 is also differentially expressed between osteoarthritis synovium cells (OASC) and rheumatoid arthritis synovium fibroblasts (RASF), and whether ndr2 can suppress the growth of RASF in vitro. Methods: Dot blotting, cell culture and gene transfection, cell cycle nalysis techniques were applied to investigate the effect of ndr2 on the cell phenotype and cell cycles. Results: ndr2 is expressed in OASC but absent in RASF. Transient transfection of ndr2 into RASF can suppress the growth of RASF from phenotype observation. Cell cycle analysis showed that apoptotic peaks can be detected in RASF cells transfected with ndr2 gene. Conclusion: Novel tumor suppressor candidate ndr2 is not only differentially expressed between OASC and RASF but also can induce the apoptosis of RASF in vitro.

  11. ROLE OF NEEDLE SYNOVIAL BIOPSY IN JOINT DISEASES

    Directory of Open Access Journals (Sweden)

    Venkataraman

    2015-05-01

    Full Text Available J oint disease is a common problem affecting all age groups presenting in orthopedic and rheumatology clinics. Diagnostic difficulties are encountered , particularly , in early stages when radiology and blood tests are inconclusive. The role of synovial analysis ( S ynovium and fluid using the Parker Pearson technique was studied in 50 patients with various j oint afflictions. There were 44 cases of monoarthritis and 6 cases of polyarthritis. Synovial fluid could be completely analyzed in 43 out of 50 cases and based on their physical , biochemical and cytological properties they were grouped as – a Non inflammat ory group b Mild to moderate inflammation and c Septic or severe inflammatory group. In this study , there were 6 cases of rheumatoid arthritis , 8 tuberculous arthritis , 16 non - specific synovitis , 4 traumatic arthritis , 4 osteoarthritis , 2 septic arthriti s , 6 normal synovium and one each of gout , villo - nodular synovitis , neuropathic joint and AVN femoral head. With Parker Pearson needle and their technique adequate representative synovial tissue could be obtained for histopathology in 41 out of 50 (82% cases. In the rest 9 cases , it was negative and open biopsy was done t o reach a diagnosis. Closed needle synovial biopsy is a simple , cost effective outpatient procedure and a helpful adjuvant for the diagnosis of joint diseases.

  12. DDR2-CYR61-MMP1 Signaling Pathway Promotes Bone Erosion in Rheumatoid Arthritis Through Regulating Migration and Invasion of Fibroblast-Like Synoviocytes.

    Science.gov (United States)

    Huang, Tong-Lie; Mu, Nan; Gu, Jin-Tao; Shu, Zhen; Zhang, Kuo; Zhao, Jin-Kang; Zhang, Cun; Hao, Qiang; Li, Wei-Na; Zhang, Wang-Qian; Liu, Nan-Nan; Zhang, Yong; Zhang, Wei; Xue, Xiao-Chang; Zhang, Ying-Qi

    2017-02-01

    Regulation of matrix metalloproteinases (MMPs) by collagen in the fibroblast-like synoviocytes (FLSs) plays a critical role in joint destruction in rheumatoid arthritis (RA). Our previous study indicated that discoidin receptor 2 (DDR2) mediated collagen upregulation of MMPs. However, the precise underlying mechanism remains unclear. We report here that CYR61, a secreted, extracellular matrix-associated signaling protein which is capable of regulating a broad range of cellular activities, including cell adhesion, migration, proliferation, and apoptosis, is significantly upregulated in collagen II-stimulated RA FLS. Further studies found that collagen II-activated phosphorylated-DDR2 induces CYR61 through activation of transcription factor activator protein 1 (AP-1). The elevated CYR61, in turn, accelerates MMP1 production via ETS1 (ETS proto-oncogene 1). In addition, CYR61 significantly promotes FLS invasion and migration. Blockade of CYR61 by an adenovirus expressing CYR61 shRNA (Ad-shCYR61) in vivo remarkably ameliorated the severity of arthritis, reduced inflammatory cytokine secretion, and attenuated bone erosion as detected by micro-computed tomography (μCT), in collagen-induced arthritis (CIA) rats. Taken together, we uncovered the Collagen II-DDR2-AP-1-CYR61-ETS1-MMP1 loop in RA FLS. In which, CYR61 acts as a hinge to promote cartilage damage through regulating FLS invasion, migration, and MMP1 production and the inflammatory cascade in RA. Thus, CYR61 may be a promising diagnostic and therapeutic target for RA treatment. © 2016 American Society for Bone and Mineral Research.

  13. CYP7B Expression and Activity in Fibroblast-Like Synoviocytes From Patients With Rheumatoid Arthritis Regulation by Proinflammatory Cytokines

    NARCIS (Netherlands)

    Dulos, John; van der Vleuten, Monique A. J.; Kavelaars, Annemieke; Heijnen, Cobi J.; Boots, Annemieke M.

    2005-01-01

    Objective. The cytochrome P450 enzyme CYP7B catalyzes the conversion of dehydroepiandrosterone (DHEA) into 7 alpha-hydroxy-DHEA (7 alpha-OH-DHEA). This metabolite can stimulate the immune response. We previously reported that the severity of murine collagen-induced arthritis is correlated with CYP7B

  14. MDM4 overexpression contributes to synoviocyte proliferation in patients with rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Nanwei [Department of Orthopaedics, The Affiliated Hospital of Nanjing Medical University, Changzhou Second People' s Hospital, Changzhou 213003 (China); Wang, Yuji, E-mail: yujiwang@sohu.com [Department of Orthopaedics, The Affiliated Hospital of Nanjing Medical University, Changzhou Second People' s Hospital, Changzhou 213003 (China); State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433 (China); Li, Dawei [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433 (China); Chen, Guoqiang, E-mail: 13929981788@139.com [Department of Rheumatology and Immunology, The First People' s Hospital of Foshan, Foshan 528000 (China); Sun, Rongbin; Zhu, Ruixia [Department of Orthopaedics, The Affiliated Hospital of Nanjing Medical University, Changzhou Second People' s Hospital, Changzhou 213003 (China); Sun, Sai [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433 (China); Liu, Hongwei [Department of Orthopaedics, The Affiliated Hospital of Nanjing Medical University, Changzhou Second People' s Hospital, Changzhou 213003 (China); Yang, Guang [Center of Research, The First People' s Hospital of Foshan, Foshan 528000 (China); Dong, Tianhua [Department of Orthopaedics, The First Affiliated Hospital of Suzhou University, Suzhou 215007 (China)

    2010-10-22

    Research highlights: {yields} Elevated MDM4 mRNA and protein levels in FLS from patients with RA and OA. {yields} Strong MDM4 staining in synovial cells of inflammatory synovium. {yields} MDM4 knockdown increased p53 and p21 levels, and inhibited the proliferation of RA FLS. {yields} MDM4 overexpression increased p53 while decreased p21 levels, and promoted the growth of RA FLS. -- Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease with features of inflammatory cell infiltration, synovial cell invasive proliferation, and ultimately, irreversible joint destruction. It has been reported that the p53 pathway is involved in RA pathogenesis. MDM4/MDMX is a major negative regulator of p53. To determine whether MDM4 contributes to RA pathogenesis, MDM4 mRNA and protein expression were assessed in fibroblast-like synoviocytes (FLS) by real-time PCR, western blotting, and in synovial tissues by immunohistochemistry. Furthermore, MDM4 was knocked down and overexpressed by lentivirus-mediated expression, and the proliferative capacity of FLS was determined by MTS assay. We found that cultured FLS from RA and osteoarthritis (OA) patients exhibited higher levels of MDM4 mRNA and protein expression than those from trauma controls. MDM4 protein was highly expressed in the synovial lining and sublining cells from both types of arthritis. Finally, MDM4 knockdown inhibited the proliferation of RA FLS by enhancing functional p53 levels while MDM4 overexpression promoted the growth of RA FLS by inhibiting p53 effects. Taken together, our results suggest that the abundant expression of MDM4 in FLS may contribute to the hyperplasia phenotype of RA synovial tissues.

  15. 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.

  16. 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...

  17. Recombinant human endostatin inhibits TNF-alpha-induced receptor activator of NF-κB ligand expression in fibroblast-like synoviocytes in mice with adjuvant arthritis.

    Science.gov (United States)

    Gao, Qiu-Fang; Zhang, Xiu-Hong; Yuan, Feng-Lai; Zhao, Ming-Dong; Li, Xia

    2016-12-01

    Bone loss is a critical pathology responsible for the functional disability in patients with rheumatoid arthritis (RA). It is well known that receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) plays a crucial role in bone loss in RA. The purpose of this study was to determine whether recombinant human endostatin (rh-endostatin) mediates bone erosion in RA by regulation of RANKL expression in an experimental model of RA, consisting of mice with adjuvant-induced arthritis (AA). Cultured AA fibroblast-like synoviocytes (FLSs) obtained from these mice were induced by tumor necrosis factor-α (TNF-α) combined with or without rh-endostatin. The levels of RANKL and osteoprotegerin (OPG) mRNA, soluble and membrane-bound proteins were assessed by real-time PCR, ELISA, and Western blotting. Western blotting and the luciferase reporter assay were used to study related signaling pathways. Rh-endostatin inhibited RANKL mRNA expression, soluble and membrane-bound protein expression in AA FLSs but not in CD4+ T cells. However, OPG expression and secretion was not affected by rh-endostatin in AA FLSs. Molecular analysis demonstrated that rh-endostatin significantly inhibited TNF-α-induced MAPK and AP-1 signaling pathways. Moreover, rh-endostatin attenuated TNF-α-induced NF-κB signaling by suppressing the phosphorylation level of inhibitor kappaBα (IκBα) and nuclear translocation of NF-κB p65 in FLSs from mice with AA. These results provide the first evidence that rh-endostatin inhibits TNF-α-induced RANKL expression in AA FLSs.

  18. Low-Molecular-Weight Fucoidan Inhibits the Viability and Invasiveness and Triggers Apoptosis in IL-1β-Treated Human Rheumatoid Arthritis Fibroblast Synoviocytes.

    Science.gov (United States)

    Shu, Zunhua; Shi, Xiaozhe; Nie, Daqing; Guan, Bingyu

    2015-10-01

    Fucoidan is a sulfated polysaccharide found mainly in various species of brown algae and brown seaweed. Here, we investigated the effects of low-molecular-weight (LMW) fucoidan (4 kDa) on interleukin-1beta (IL-1β)-stimulated rheumatoid arthritis fibroblast-like synoviocyte (RAFLS). 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and annexin V/propidium iodide assay were used to assess cell viability and apoptosis, respectively. Transwell assay was performed to evaluate cell invasion. Reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay analysis was done to measure gene expression and secretion. Nuclear factor-kappa B (NF-κB) DNA binding activity was determined by electrophoretic mobility shift assay. LMW fucoidan dose-dependently inhibited the viability and induced apoptosis of IL-1β-treated RAFLS. Fucoidan attenuated IL-1β-induced invasion of RAFLS and decreased the expression and secretion of metalloproteinase (MMP)-1, MMP-3, and MMP-9. Fucoidan suppressed NF-κB binding activity, p65 nuclear translocation, and IκB-α degradation in IL-1β-stimulated RAFLS. Additionally, IL-1β-induced phosphorylation of p38 but not ERK or JNK was significantly impaired by fucoidan treatment. LMW fucoidan reduces the viability, survival, and invasiveness of IL-1β-treated RAFLS, which is associated with inhibition of NF-κB and p38 activation. LMW fucoidan may have therapeutic potential in the treatment of rheumatoid arthritis.

  19. Giant Synovial Cyst of Thigh: A Rare Entity

    Directory of Open Access Journals (Sweden)

    Kushagra Sinha

    2013-01-01

    Full Text Available Synovial cyst occurs secondary to traumatic, degenerative, or inflammatory conditions. Synovial cysts represent abnormal distension of bursae, which communicate with the joint. Giant synovial cysts are typically due to rheumatoid arthritis, other causes being trauma and synovial pseudoarthrosis. A 33-year-old male presented to an outpatient clinic with a massive swelling on his posterolateral aspect of right thigh extending from upper one-third to the knee joint which had been increasing in size over the past six months. This was associated with dull aching pain. All laboratory investigations were within normal parameters. Even FNAC was inconclusive. With time, swelling was increasing in size. Ultrasound revealed the cystic nature of swelling. MRI showed large cystic lesion 24 × 10 × 12 cm in posterolateral aspect of thigh extending up to knee joint. Following the MRI, an excision was planned. After excision, histological examination confirmed the synovial nature of the cyst, which had a collagenous wall and dense chronic inflammatory cells. As the disease is extremely rare and asymptomatic, precise diagnosis is difficult and often delayed. We consider that open surgical excision should be reserved for cases of large synovial cysts because it can provide a complete resection of the lesion and minimize the risk of recurrence.

  20. 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

    -modifying antirheumatic drug (DMARD) therapy alone (11 patients) or DMARDs in combination with oral prednisolone (15 patients), were followed up for 1 year with contrast-enhanced MRI of the dominant wrist (months 0, 3, 6, and 12), conventional radiography (months 0 and 12), and clinical and biochemical examinations. Bone...... erosion (by MRI and radiography) and synovial membrane volumes (by MRI) were assessed. RESULTS: Significant synovial membrane volume reductions were observed after 3 and 6 months in the DMARD + prednisolone group, and after 6 and 12 months in the DMARD-alone group (P ...-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

  1. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    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.

  2. Synovial hemangioma: A rare benign synovial lesion

    Directory of Open Access Journals (Sweden)

    Rajni

    2008-04-01

    Full Text Available We report an unusual case of a 10-year-old female with complaints of pain and swelling of the right knee for the last 4 years along with the limitation of movement for last 1 year. Repeated fine needle aspirations yielded blood and a provisional diagnosis of hemarthrosis was suggested. Coagulation profile subsequently carried out was found to be within normal limits. Arthroscopic biopsy was performed and tissue was sent for histopathological examination. A diagnosis of synovial hemangioma was made. Subtotal synovectomy was performed and the lesion was completely excised. The patient is completely asymptomatic and shows no signs of recurrence at 1 year.

  3. 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....

  4. 类风湿性关节炎患者血清及关节积液SOCS-1、SOCS-3蛋白的含量检测及意义%The content and value of SOCS-1 and SOCS-3 proteins in serum and synovial fluid of patients with rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    林栋; 汪铁军; 钱一龙

    2012-01-01

    Objective To investigate the changes of the levels of serum and synovial fluid SOCS-1, SOCS-3 in patients with rheumatoid arthritis( RA ), and to explore the value of SOCS-1 and SOCS-3 in inflammatory reaction of rheumatoid arthritis. Methods 49 patients with rheumatoid arthritis were divided into active RA group( 26 cases ) and non- active RA group( 23 cases jaccording to disease activity index. The levels of serum and synovial fluid SOCS-1, SOCS-3 were detected by ELISA, while the 20 health)' control were compiled into the control group. Results The levels of serum SOCS-1 and SOCS-3 were significantly higher in RA group than those in control group( P < 0. 01 ), which were significantly higher in active RA group than those in non- active RA group( P < 0. 01, P < 0. 05 ). The levels of synovial fluid SOCS-1 and SOCS-3 were significantly higher in active RA group than those in non- active RA group( P <0. 05 ). The levels of serum SOCS-1 and SOCS-3 were positively correlated with the serum ESR,CRP,RF ( P <0. 01 ,P <0. 05 ). Conclusions SOCS-1 and SOCS-3 may play an important role in the pathological process of inflammatory response in rheumatoid arthritis, which ma)' be related to activity of rheumatoid arthritis.%目的 观察类风湿性关节炎(RA)患者血清及关节液SOCS-1、SOCS-3蛋白含量的变化,探讨其在炎症中的意义.方法 49例类风湿性关节炎患者根据疾病活动性分为活动期组(26例)及缓解期组(23例),采用ELISA法检测其血清及关节液SOCS-1、SOCS-3蛋白含量,并与20例健康体检者(对照组)进行比较.结果 与对照组比较,RA患者中活动期组与缓解期组血清SOCS-1、SOCS-3蛋白含量均明显升高(P<0.01),其中活动期组血清SOCS-1、SOCS-3含量表达较缓解组明显升高(P<0.01、P<0.05);活动期组患者关节积液SOCS-1、SOCS-3蛋白表达较缓解期组明显升高(P<0.05);活动期组患者血清SOCS-1、SOCS-3蛋白水平均与血清ESR、CRP、RF呈正相关(P<0.01、P<0

  5. The potential use of microcalorimetry in rapid differentiation between septic arthritis and other causes of arthritis.

    Science.gov (United States)

    Yusuf, E; Hügle, T; Daikeler, T; Voide, C; Borens, O; Trampuz, A

    2015-03-01

    Current diagnostic methods in differentiating septic from non-septic arthritis are time-consuming (culture) or have limited sensitivity (Gram stain). Microcalorimetry is a novel method that can rapidly detect microorganisms by their heat production. We investigated the accuracy and time to detection of septic arthritis by using microcalorimetry. Patients older than 18 years of age with acute arthritis of native joints were prospectively included. Synovial fluid was aspirated and investigated by Gram stain, culture and microcalorimetry. The diagnosis of septic arthritis and non-septic arthritis were made by experienced rheumatologists or orthopaedic surgeons. Septic arthritis was diagnosed by considering the finding of acute arthritis together with findings such as positive Gram stain or positive culture of synovial fluid or positive blood culture. The sensitivity and specificity for diagnosing septic arthritis and the time to positivity of microcalorimetry were determined. Of 90 patients (mean age 64 years), nine had septic arthritis, of whom four (44 %) had positive Gram stain, six (67 %) positive synovial fluid culture and four (44 %) had positive blood culture. The sensitivity of microcalorimetry was 89 %, the specificity was 99 % and the mean detection time was 5.0 h (range, 2.2-8.0 h). Microcalorimetry is an accurate and rapid method for the diagnosis of septic arthritis. It has potential to be used in clinical practice in diagnosing septic arthritis.

  6. Pathophysiology and imaging in inflammatory and blastomatous synovial diseases

    Energy Technology Data Exchange (ETDEWEB)

    Imhof, H.; Noebauer-Huhmann, I.-M.; Gahleitner, A.; Kainberger, F.; Krestan, C.; Trattnig, S. [Osteology, Universitaets Klinik fuer Radiodiagnostik, AKH Vienna (Austria); Sulzbacher, I. [Klinisches Institut fuer klinische Pathologie, AKH Vienna (Austria)

    2002-06-01

    Variable pathologies are subsumed under the term ''synovial disease'', including common pathologies such as rheumatoid arthritis. While formerly radiologists had to rely on conventional radiographs and bone scintigraphy with their inherent problems in visualizing soft tissue, noninvasive imaging of the synovium has recently improved substantially with the technical development of MRI and (Doppler) ultrasound. These imaging modalities allow differentiation of characteristic pathologic features based on a profound knowledge of normal anatomy and pathophysiology. (orig.)

  7. [Pathogenesis of rheumatoid arthritis].

    Science.gov (United States)

    Branimir Anić; Miroslav Mayer

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune systemic disease that primarily affects joints. Etiology and the pathogenesis of RA are complex, involving many types of cells, among others macrophages, T and B cells, fibro- blasts, chondrocytes and dendritic cells. Despite well documented role of many genes and epigenetic modifications in the development and evolution of the disease, in most RA patients there is no clear predisposing factor present. Environmental factors involved in RA pathogenesis are cigarette smoke, industrial pollutants like silica crystals, disturbances of intestinal, lung, and oral microbiota and some specific bacterial and viral infectious agents and their components. In the initial disease stage there are qualitative and quantitative disturbances ofpeptide citrulination as well as other protein modifications, followed by antigen presenting cell (APC) (macrophages and dendritic cells) and fibroblast like synoviocytes (FLS) activation. Some microbes foster this processes by APC and FLS direct and indirect activation. In the second stage APC's elicit specific humoral B cell re- sponse resulting in specific antibodies production and T cell autoreactivity. Inherited and acquired defects in T and B cell responses caused by repeated activation of innate immunity as well as loss of tolerance, elicit chronic autoimmune inflammation, primarily of synovial membranes, and development of cellular panus. Pathologic activation of the osteoclasts and release of the immune system effector molecules and the proteolytic enzymes damage the cartilage, bone and tendons composition and structure. Persistent inflammation through its complex mechanisms results in many systemic and extraarticular RA manifestations of almost all organ systems, resulting in severe complications and comorbidities such as rheumatoid lung, carditis, vasculitis, cahexia, anemia, accelerated atherosclerosis, myocardial and cerebrovascular vascular disease, lymphoma, osteoporosis, depression etc

  8. Septic manubriosternal arthritis in a patient with Reiter's disease.

    Science.gov (United States)

    Van Linthoudt, D; De Torrente, A; Humair, L; Ott, H

    1987-06-01

    A man with a quiescent Reiter's disease presented with abrupt upper chest pain. This symptom resulted from a septic arthritis of the manubriosternal joint due to staphylococcus aureus cultured from the synovial fluid.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. TWEAK promotes the production of Interleukin-17 in rheumatoid arthritis.

    Science.gov (United States)

    Park, Jin-Sil; Park, Mi-Kyung; Lee, Seon-Yeong; Oh, Hye-Jwa; Lim, Mi-Ae; Cho, Woo-Tae; Kim, Eun-Kyung; Ju, Ji-Hyeon; Park, Young-Woo; Park, Sung-Hwan; Cho, Mi-La; Kim, Ho-Youn

    2012-10-01

    Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is an inflammatory cytokine that modulates several biological responses by inducing chemokines and proinflammatory cytokines. We hypothesized that TWEAK could promote secretion of IL-17, an amplifier of inflammatory arthritis. To test this, we investigated the capacity of TWEAK to induce IL-17 production in T cells via the fibroblast growth factor-inducible gene 14 (Fn14, also known as TWEAK receptor) signal pathway in rheumatoid arthritis (RA). Fn14 and IL-17 were highly expressed in arthritic tissues of collagen-induced arthritis (CIA) mice. TWEAK induced production of IL-17 alone and synergistically with lipopolysaccharide. In naïve murine T cells, TWEAK promoted Th17 differentiation. The expression of Fn14 was predominant in Th17 cells. TWEAK and IL-17 concentrations were significantly higher in synovial fluid and serum in RA patients than OA patients. In addition, we identified CD4(+)IL-17(+)Fn14(+) cells in synovium from RA patients. TWEAK promoted IL-17 production synergistically with IL-23 or IL-21 and blockade of Fn14 with Fn14-Fc suppressed Th17 differentiation. Conversely, this treatment enhanced Treg differentiation. These results suggest that TWEAK induces IL-17 production and may be a therapeutic target in the treatment of RA.

  12. Development of synovial membrane in the temporomandibular joint of the human fetus

    Directory of Open Access Journals (Sweden)

    L.O. Carvalho de Moraes

    2015-11-01

    Full Text Available The development of the synovial membrane was analyzed in serial sections of 21 temporomandibular joints of human fetuses at 9 to 13 weeks of gestation. Sections of two fetuses at 12 weeks of development were used to perform immunohistochemical expression of the markers CD68 and Hsp27 on the synovial lining. Macrophage-like type A and fibroblast-like type B cells, which express CD68 and Hsp27, respectively, were observed at the twelfth week of development. Our results suggest that the development of the synovial membrane is related to the vascularization of the joint and the formation of the articular cavities.

  13. Development of synovial membrane in the temporomandibular joint of the human fetus.

    Science.gov (United States)

    Carvalho de Moraes, L O; Tedesco, R C; Arraez-Aybar, L A; Klein, O; Mérida-Velasco, J R; Alonso, L G

    2015-11-26

    The development of the synovial membrane was analyzed in serial sections of 21 temporomandibular joints of human fetuses at 9 to 13 weeks of gestation. Sections of two fetuses at 12 weeks of development were used to perform immunohistochemical expression of the markers CD68 and Hsp27 on the synovial lining. Macrophage-like type A and fibroblast-like type B cells, which express CD68 and Hsp27, respectively, were observed at the twelfth week of development. Our results suggest that the development of the synovial membrane is related to the vascularization of the joint and the formation of the articular cavities.

  14. Synovial chondromatosis in raptors.

    Science.gov (United States)

    Stone, E G; Walser, M M; Redig, P T; Rings, B; Howard, D J

    1999-01-01

    Fourteen raptors, consisting of 13 great horned owls (Bubo virginianus) and one red-tailed hawk (Buteo jamaicensis), from central and north central Minnesota, western Wisconsin, and eastern South Dakota (USA) were admitted to a raptor rehabilitation center between June 1992 and June 1995, with perisynovial and synovial chondromatosis affecting multiple joints. Birds were severely debilitated primarily due to loss of shoulder motion. The etiology of these lesions in raptors is unknown.

  15. 共培养下前交叉韧带成纤维细胞中LOXs与MMPs的基因表达情况%Gene Expressions of LOXs and MMPs of the ACL Fibroblasts Cells Co-cultured with Synovial Cells

    Institute of Scientific and Technical Information of China (English)

    王春莉; 梅虎; 谢静; 蒋稼欢; 陈荣富; 尹琳; 符纯锋; 陈诚; 宋国立

    2013-01-01

    The progress of research on the the anterior cruciate ligament (ACL) wound healing demonstrates that the synovial tissue in the knee joint plays a very important role in the healing process of injured ACL.Therefore,the molecular response mechanisms of lysyl oxidase (LOX) and matrix metalloproteina (MMP) in normal/injured ACL fibroblast cells could be considered to perform the major analysis function of injured ACL healing mechanism.The mRNA expressions of LOXs and MMPs and the activity expressions of MMP-2 in ACL fibroblasts co-cultured with synovial cells were analyzed by quantitative real-time PCR and zymography.The results showed that co-culture could regulate the mRNA expressions of LOXs and MMPs in the ACL fibroblasts cells.These results suggest that the differential expressions of LOXs and MMP-1,2,3 in co-cultured ACL indicate that interaction crosstalk do exist between ACL cells and synovial cells and provide a theoretical basis for subsequent exploration of the mechanisms and treatment of ACL injury and repair.%前交叉韧带(ACL)损伤修复的研究进展表明,膝关节内覆在ACL上的滑膜组织对ACL损伤修复起到非常重要的作用.为探讨滑膜细胞对ACL成纤维细胞中影响组织修复的关键酶即赖氨酰氧化酶(LOXs)与基质金属蛋白酶(MMPs)表达及活性的影响,本文通过建立体外ACL成纤维细胞与滑膜细胞共培养体系,采用RT-PCR与明胶酶谱(zemography)技术定量分析比较单培养与共培养ACL成纤维细胞中LOXs与MMP-1、2、3基因的表达情况及MMP-2蛋白酶的活性.结果显示:(1)共培养促进ACL成纤维细胞中的LOXs与MMP-2的基因表达,但降低MMP-1、MMP-3的基因表达.(2)与单培养组相比,在不同时间点,共培养组都促进ACL成纤维细胞中MMP-2蛋白酶的表达及其活化程度.以上结果表明:ACL细胞和滑膜细胞之间存在密切的交流影响了LOXs与MMP-1、2、3的基因表达,为后续探索ACL损伤修复的机制及治疗方法提供了理论依据.

  16. Relation Analysis of Synovial Anti-Citrullinated Epitope Peptide Expression and Peptidyl Arginine Deiminase 4 Gene in the Rheumatoid Arthritis Patient%类风湿关节炎患者滑膜抗环瓜氨酸肽表位表达与肽酰基精氨酸脱亚氨酶4基因的相关性分析

    Institute of Scientific and Technical Information of China (English)

    沈小辉; 喻伟; 杨菲

    2016-01-01

    Objective To investigate the relation of synovial anti-citrullinated epitope peptide(CCP)expression and peptidyl arginine deiminase 4 (PADI4)gene in the rheumatoid arthritis patient.Methods From February 2013 to 2015 in Dongfeng General Hospital Affiliated to Hubei University,selected 110 patients with rheumatoid arthritis as the observation group, and selected 110 healthy people at the same period in this hospital for medical examination as the control group,both groups were given the synovial CCP expression positive rate and PADI4 gene expression detecting and correlation analysis.Results The synovial anti-CCP expression positive rates in the observation group and the control group were 70.9% and 9.1% re-spectively,and the observation group were significantly higher than the control group (P<0.05).The PADI4-104 genotype expression frequency compared between the observation group and control group,the difference were statistically significant (P<0.05).The G/G expression was more in the observation group,while the control group was more wit the C/G expres-sion.Pearson correlation analysis showed that in the observation group,synovial CCP positive expression were significant correlated to the expression of genotype PADI4-104 (r=0.344,P<0.05).Logistic regression analysis showed PADI4-104 genotype frequency were the main factors for the synovial CCP epitope expression (P<0.05).Conclusion The rheumatoid arthritis was more with synovial anti-CCP positive expression.There were also PADI4 polymorphism disorder expression, and clear correlation between the two.Thus impact the incidence of rheumatoid arthritis.%目的探讨类风湿关节炎患者滑膜抗环瓜氨酸肽(CCP)表位表达与肽酰基精氨酸脱亚氨酶4(PADI4)基因的相关性。方法2013年2月~2015年选择在湖北医药学院附属东风医院风湿免疫科住院的类风湿关节炎患者110例作为观察组,同期选择在该院进行体检的健康者110例作为对照

  17. Oxidative stress-induced DNA damage in the synovial cells of the temporomandibular joint in the rat.

    Science.gov (United States)

    Yamaza, T; Masuda, K F; Atsuta, I; Nishijima, K; Kido, M A; Tanaka, T

    2004-08-01

    Synovial hyperplasia is a feature of degenerative temporomandibular joint (TMJ) disease. However, the mechanism by which hyperplasia progresses in the TMJ is unknown. Based on the hypothesis that the oxidative stress generated by mechanical loading causes degenerative changes in the TMJ synovium, we investigated the generation of the highly reactive species, peroxynitrite, and the occurrence of DNA damage in the synovium. After condylar hypermobility of rat TMJs, a marker of peroxynitrite, nitrotyrosine, was localized to the nuclei and cytoplasm of the synovial lining cells and fibroblasts in synovitis-induced TMJ. DNA single-strand breaks were found in the nuclei of the synovial cells only after enzyme treatment, whereas DNA double-strand breaks were not detected. These findings indicate that condylar hypermovement induces the proliferation of synovial cells, and suggest that oxidative stress leads to the progression of synovial hyperplasia via DNA damage of the synovial cells in TMJs after mechanical loading.

  18. Detection of BRAF in the synovial fluid and its clinical significance in rheumatoid arthritis%鼠科肉瘤病毒癌基因同源物B1蛋白在类风湿关节炎滑液中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    赵金霞; 孙琳; 张颖健; 张霞; 李茹; 刘湘源

    2013-01-01

    Objective To detect v raf murine sarcoma viral oncogene homologue B1 (BRAF) in the synovial fluid of rheumatoid arthritis (RA) and to investigate its clinical significance in RA.Methods Synovial fluid samples were obtained from patients with RA and osteoarthritis (OA).Serum samples were obtained from patients with RA,OA and heathy controls.The presence of BRAF in the synovial fluid and sera were examined by enzyme-linked immunosorbent assay (ELISA).Western blotting was used to detect the expression of BRAF protein in the synovial tissue of RA and OA.The associations between the BRAF and the clinical features and laboratory parameters of RA were evaluated.Data analysis were performed using t test and Spearman's association analysis.Results ① The level of BRAF in the synovial fluid of RA [(84±59) ng/ml] was significantly higher than OA [(38±41) ng/ml] (t=3.290,P=0.002).② The level of BRAF in the sera of RA patients [(22.0±12.5) ng/ml] was also higher than OA [(6.8±7.5) ng/ml,t=3.882,P<0.01] and healthy controls [(4.8±2.2) ng/ml,t=6.766,P<0.01].③ In RA patients,the BRAF protein level in the synovial fluid [(102±52) ng/ml] was significantly higher than that in the serum [(21±12) ng/ml] (t=-4.316,P=0.003).④The expression level of BRAF in the synovial tissue of RA (0.284±0.045) was higher than that in OA patients (0.191±0.013,t=3.169,P=0.034).⑤ The level of BRAF in the synovial fluid had a negative correlation with disease duration (r=-0.40,P=0.019) and a positive correlation with rheumatoid factor (RF) levels (r=0.37,P=0.03).Conclusion The presence of BRAF in the synovial fluid and synovium of RA indicates that BRAF may play a role in the pathogenesis of RA,especially in the early stage.%目的 检测类风湿关节炎(RA)患者滑液中鼠科肉瘤病毒癌基因同源物B1(BRAF)蛋白水平,探讨其在RA中的临床意义.方法 应用酶联免疫吸附法(ELISA)检测44例RA患者及22例骨关节炎患者滑

  19. Predictors of Septic Arthritis in the Adult Population.

    Science.gov (United States)

    Borzio, Robert; Mulchandani, Neil; Pivec, Robert; Kapadia, Bhaveen H; Leven, Dante; Harwin, Steven F; Urban, William P

    2016-07-01

    Septic arthritis is a devastating condition; well-established criteria for diagnosis exist in the pediatric population, but not for adults. This study evaluated patient factors and laboratory parameters that may be associated with the diagnosis of septic arthritis in adults. A total of 458 knee aspirates for suspected septic arthritis were evaluated with serum and synovial leukocyte counts and differentials as well as Kocher criteria for pediatric septic arthritis. Twenty-two patients (4.8%) had septic arthritis confirmed by a positive synovial fluid culture. Erythrocyte sedimentation rate (ESR) and serum white blood cell (WBC) counts were not statistically different between the 2 groups, with 64% of septic arthritis patients having a normal serum WBC count and 77% being afebrile. Mean synovial fluid WBC count was 26,758 cells/µL and 70,581 cells/µL in the nonseptic and septic groups, respectively. The likelihood ratio for a synovial fluid WBC count greater than 65,000 cells/µL was 2.8 (95% confidence interval, 1.2-6.7). Evaluation receiver operating characteristic curves using synovial WBC counts resulted in a significant area under the curve of 0.66 (P=.02). To achieve 90% specificity, a WBC cutoff of 64,000 cells/µL was required with a corresponding sensitivity of 40%. There was no significant difference in the synovial cell differential of 80% vs 90% in diagnosing infection. Synovial fluid WBC count greater than 64,000 cells/µL yielded the optimal combination of sensitivity and specificity. Polymorphonuclear leukocytes, ESR, serum WBC count, fever, and weight-bearing status were not significant predictors of septic arthritis. This study demonstrates the limited utility of Kocher criteria in the adult population and the importance of synovial leukocyte counts. [Orthopedics. 2016; 39(4):e657-e663.].

  20. Staphylococcal septic arthritis in three horses.

    Science.gov (United States)

    Rose, R J; Love, D N

    1979-04-01

    Three horses were diagnosed as having monarticular septic arthritis due to Staphylococcus aureus on the basis of culture of articular cartilage, synovial membrane and/or synovial fluid. The organisms were all well recognised human phage types and in two cases demonstrated beta-lactamase (penicillinase) activity. Details of case histories are presented and the bacteriological techniques and antibiotic management with cloxacillin, methicillin and penicillin discussed. Following treatment, sterile cultures of synovial fluid were achieved in all cases, but in two horses the infections resulted in degenerative articular changes. This necessitated arthrodesis of the fetlock joint in one case.

  1. [Synovial sarcoma. Case report].

    Science.gov (United States)

    Deme, Dániel; Abdulfatah, Bishr; Telekes, András

    2016-02-07

    In 2013 there were 94,770 new cancer patients reported in Hungary. Synovial sarcoma accounts for 0.05-0.1% of all cancers and, therefore its incidence is predicted to be 47-94 patients/year in Hungary. The authors report the history of a 18-year-old man who was operated on a right upper abdominal wall tumor with R1 resection. During the next 5 months the tumor grew up to 8 cm in largest diameter. Histology revealed monophasic synovial sarcoma. Immunohistochemistry showed bcl2, focal CD99 and high molecular weight cytokeratin positivity, while smooth muscle actin, S100 and CD34 immunostainings were negative. Becose of this reoperation was not possible, curative six cycles of doxorubicine and ifosfamide with granulocyte colony stimulating factor support and 60 Gy radiotherapy was given to the tumor bed. After these treatments computed tomography scan was negative and the patient attended regular imaging every 3 months. At the age of 20 years the patient developed two neoplastic lesions in the surgical scar measuring 10 mm and 45 × 10 mm in size. R0 resection, partial rib resection and abdominal wall reconstruction were performed. Histology confirmed residual monophasic synovial sarcoma. Radiotherapy was not given because of a risk of intestinal wall perforation. Staging positron emission tomography-computed tomography proved to be negative. At the age of 22 years magnetic resonance imaging scans indicated no tumor recurrence, but after one month a rapidly growing tumorous lesion was found on ultrasound in the surgical scar measuring 20 × 20 × 12 mm in size. Cytology confirmed local recurrence and fluorescence in situ hibridization indicated t(x;18). R0 exstirpation and partial mesh resection were performed and histology showed the same monophasic synovial sarcoma. Because of the presence of vascular invasion and a close resection margin (1 mm) the patient underwent 3 cycles of adjuvant chemotherapy (doxorubicine and ifosfamide) with granulocyte colony stimulating

  2. IL33 in rheumatoid arthritis: potential contribution to pathogenesis.

    Science.gov (United States)

    Macedo, Rafaela Bicalho Viana; Kakehasi, Adriana Maria; Melo de Andrade, Marcus Vinicius

    A better understanding of the inflammatory mechanisms of rheumatoid arthritis and the development of biological therapy revolutionized its treatment, enabling an interference in the synovitis - structural damage - functional disability cycle. Interleukin 33 was recently described as a new member of the interleukin-1 family, whose common feature is its pro-inflammatory activity. Its involvement in the pathogenesis of a variety of diseases, including autoimmune diseases, raises the interest in the possible relationship with rheumatoid arthritis. Its action has been evaluated in experimental models of arthritis as well as in serum, synovial fluid and membrane of patients with rheumatoid arthritis. It has been shown that the administration of interleukin-33 exacerbates collagen-induced arthritis in experimental models, and a positive correlation between cytokine concentrations in serum and synovial fluid of patients with rheumatoid arthritis and disease activity was found. This review discusses evidence for the role of interleukin-33 with a focus on rheumatoid arthritis.

  3. CLINICO-PATHOLOGICAL STUDY OF INFLAMMATORY SYNOVIAL LESIONS OF KNEE JOINT

    Directory of Open Access Journals (Sweden)

    Mamatha

    2015-12-01

    Full Text Available INTRODUCTION Synovial joints account for most of body’s articulation and characterised by wide range of almost frictionless movements. Synovium is the central area of pathology in a number of inflammatory joint diseases. Joint effusions present as diagnostic challenge to physicians and need careful evaluation and interpretation of both clinical and laboratory findings to make accurate diagnosis and avoid unnecessary hospital stay. Joint effusions present as diagnostic challenge to physicians and requiring careful evaluation and interpretation of both clinical and laboratory findings to make accurate diagnosis to avoid unnecessary hospital stay. AIM OF THE STUDY Is to study the diagnostic features joint effusion in cases of inflammatory synovitis of the knee joint. MATERIALS AND METHODS Prospective study was done over a period of two years in the Department of Pathology in a tertiary care hospital. Joint fluid was obtained by arthrocentesis in patients with joint effusions. Gross, microscopic, microbiological and biochemical parameters were examined in 50 samples of synovial fluids with synovial biopsy correlation. RESULTS Out of 50 cases, 20 cases were rheumatoid arthritis, 12 cases of chronic inflammatory arthritis not specified. 10 cases tuberculous arthritis, septic arthritis in 7 cases and gout 1 case. CONCLUSION Combination of clinical, radiological, serological, biochemical and microbiologic findings along with synovial fluid and biopsy findings help in diagnosis of specific inflammatory lesions of the synovium and treating the particular condition.

  4. Condromatose sinovial Synovial chondromatosis

    Directory of Open Access Journals (Sweden)

    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.

  5. 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....

  6. Ultrasonographic findings in 38 horses with septic arthritis/tenosynovitis.

    Science.gov (United States)

    Beccati, Francesca; Gialletti, Rodolfo; Passamonti, Fabrizio; Nannarone, Sara; Di Meo, Antonio; Pepe, Marco

    2015-01-01

    Septic arthritis/tenosynovitis in the horse can have life-threatening consequences. The purpose of this cross-sectional retrospective study was to describe ultrasound characteristics of septic arthritis/tenosynovitis in a group of horses. Diagnosis of septic arthritis/tenosynovitis was based on historical and clinical findings as well as the results of the synovial fluid analysis and/or positive synovial culture. Ultrasonographic findings recorded were degree of joint/sheath effusion, degree of synovial membrane thickening, echogenicity of the synovial fluid, and presence of hyperechogenic spots and fibrinous loculations. Ultrasonographic findings were tested for dependence on the cause of sepsis, time between admission and beginning of clinical signs, and the white blood cell counts in the synovial fluid. Thirty-eight horses with confirmed septic arthritis/tenosynovitis of 43 joints/sheaths were included. Degree of effusion was marked in 81.4% of cases, mild in 16.3%, and absent in 2.3%. Synovial thickening was mild in 30.9% of cases and moderate/severe in 69.1%. Synovial fluid was anechogenic in 45.2% of cases and echogenic in 54.8%. Hyperechogenic spots were identified in 32.5% of structures and fibrinous loculations in 64.3%. Relationships between the degree of synovial effusion, degree of the synovial thickening, presence of fibrinous loculations, and the time between admission and beginning of clinical signs were identified, as well as between the presence of fibrinous loculations and the cause of sepsis (P ≤ 0.05). Findings indicated that ultrasonographic findings of septic arthritis/tenosynovitis may vary in horses, and may be influenced by time between admission and beginning of clinical signs.

  7. Methotrexate affects HMGB1 expression in rheumatoid arthritis, and the downregulation of HMGB1 prevents rheumatoid arthritis progression.

    Science.gov (United States)

    Li, Yuan-Bo; Xu, Peng; Xu, Ke; Cai, Yong-Song; Sun, Meng-Yao; Yang, Le; Sun, Jian; Lu, She-Min

    2016-09-01

    High-mobility group box 1 (HMGB1) is associated with the development of rheumatoid arthritis (RA). Recent studies have shown that methotrexate (MTX) may inhibit the expression of HMGB1. This study examined whether HMGB1 might be involved in the treatment of RA using MTX. Synovial tissues were collected from RA patients who were treated with MTX for at least 6 months (RA-MTX group, 7 cases) and from those without MTX treatment (RA-noMTX group, 7 cases). Additionally, patients with osteoarthritis (OA group, 7 cases) were used as controls. The expression and locations of HMGB1 in the tissues were detected using real-time PCR, western blot, and immunohistochemistry. Additionally, OA-fibroblast-like synoviocytes (FLSs) and RA-FLSs were isolated and cultured, and the expression of HMGB1 was reduced in these cells by transfection with HMGB1 siRNA. Cell proliferation, migration, and invasion abilities were detected. Furthermore, the effects of HMGB1 on matrix metalloproteinase (MMP)-2 and MMP-13 were measured using western blot analysis. At the tissue level, HMGB1 expression in synovial membrane did not differ significantly between the OA and RA-MTX groups, but was significantly lower in these groups than in the RA-noMTX group. In cell experiments, the cell doubling time in the RA-FLS HMGB1 siRNA group was significantly extended compared with that in the RA-FLS negative control (NC)-siRNA group. The amount of cell migration and invasion in the RA-FLS HMGB1 siRNA group was significantly lower compared with that in the NC-siRNA group; the MMP-2 and MMP-13 expression levels were also lower. These results showed that MTX reduced HMGB1 expression in RA synovial tissues, and through the downregulation of HMGB1 expression in tissues, MTX may slow disease progression of RA.

  8. 超声空化效应破坏兔胶原诱导性关节炎滑膜血管翳的实验研究%Destruction of Synovial Pannus of Antigen-induced Arthritis by Ultrasonic Cavitation in Rabbits

    Institute of Scientific and Technical Information of China (English)

    张凌燕; 邱逦; 王磊; 林玲; 文晓蓉

    2011-01-01

    Objective To optimize the conditions of ultrasonic irradiation and microbubble of ultrasound cavitation on destruction of synovial pannus of antigen-induced arthritis (AIA) in rabbits. Methods 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. Results 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. Conclusion Under optimal ultrasonic irradiation and microbubble conditions, ultrasonic cavitation could destroy synovial pannus of AIA in rabbits.%目的 探讨超声空化效应破坏兔胶原诱导关节炎滑膜血管翳的最适超声辐照及微泡条件.方法 建立双侧兔膝关节胶原诱导关节炎模型(AIA模型),将85只造模成功兔随机分入不同超声峰值负压、不同脉冲宽度、不同脉冲重复频率、不同超声辐照时间、不同微泡浓度、不同辐照次数组,经兔耳缘静脉

  9. Arthritis - resources

    Science.gov (United States)

    Resources - arthritis ... The following organizations provide more information on arthritis : American Academy of Orthopaedic Surgeons -- orthoinfo.aaos.org/menus/arthritis.cfm Arthritis Foundation -- www.arthritis.org Centers for Disease Control and Prevention -- www. ...

  10. Inducible nitric oxide synthase is expressed in synovial fluid granulocytes.

    Science.gov (United States)

    Cedergren, J; Forslund, T; Sundqvist, T; Skogh, T

    2002-10-01

    The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure l-arginine and l-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess' reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0.001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. l-arginine was elevated in SF compared to serum (257 +/- 78 versus 176 +/- 65 micro mol/l, P = 0.008), whereas a slight increase in l-citrulline (33 +/- 11 versus 26 +/- 9 micro mol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19.2 +/- 20.7 versus 8.6 +/- 6.5 micro mol/l, P = 0.054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis.

  11. Infuence of heterogenous cord blood stem cell on the morphosis of synovial membrane histopathological in model mice with arthritis induced by collagen%异种脐血干细胞对胶原诱导关节炎小鼠滑膜组织形态结构影响的研究

    Institute of Scientific and Technical Information of China (English)

    牛广华; 高玉洁; 高明利; 郭鹤; 明彩荣; 严峰

    2012-01-01

    Objective To observe histopathological changes of synovial membrane in type Ⅱ collagen-induced arthritis (CIA) modle mice,treated with transplantation of heterogenous allogeneic cord blood stem cells(HMSCs). Methods (DCD34 + cord blood stem cells were selected and identificated with FAcscaliburTM flow cytometry sorting system of BD company. (2) CIA modle mice were induced by Freund's adjuvant and type Ⅱ collagen. All 50 mice were divided into 5 groups,including normal group,model group,mono-MSCs group,double-MSCs group and MTX group(10 mice for each group). (3)Mice in mono-MSCs and double-MSCs group were injected with MSCs,with CD34 + cells for 2×103 ,through caudal vein,but normal group and model group were infected instead with 0. 9% normal saline. (4)Arthritis symptoms,osteoarthritis index and joint swelling degree of rheumatoid arthritis were observed for 42d in each group. (5)The histopathological change of synovial membrane on ankle joint was observed on the fort- second day,and the data was collected and analyzed. Results Double-MSCs transplantation was superior to mono-MSCs (P< 0. 05). Conclusion Double-MSCs could be a new source of cell transplantation for the therapy of auto-immune disease.%目的 探讨异种、异基因脐血干细胞(HMSCs)移植对小鼠Ⅱ型胶原性关节炎(CIA)滑膜组织病理学的影响.方法 (1)应用美国BD公司FAcscaliburTM型分选式细胞分析仪,进行脐血CD34+细胞分选.(2)弗氏完全佐剂+Ⅱ型胶原诱导CIA小鼠模型,随机分为正常对照组、模型组、单份HMSCs移植治疗组、双份HMSCs移植治疗组、甲氨喋呤治疗阳性对照组,每组10只小鼠.(3) 采用尾静脉注射,除模型组、正常对照组用生理盐水,单份、双份人脐血所含的CD34+ 细胞数均为2×105.(4)观察42 d不同分组小鼠的关节症状及进行关节炎指数测定.(5)移植后第42天全部处死动物取踝关节进行病理组织学检测,收集数据并作统计分析.结果 双

  12. Value of contrast-enhanced ultrasound in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Clinical management of septic arthritis in cattle.

    Science.gov (United States)

    Desrochers, André; Francoz, David

    2014-03-01

    Synovial fluid, ultrasound, and radiographic imaging are common diagnostic tools for septic arthritis. Mycoplasma septic arthritis is suspected in calves with clinical signs of otitis and pneumonia. Commonly affected joints are carpus, stifle, and tarsus. Treatment strategy must include long-term antibiotics, anti-inflammatories, and joint lavage. Knowledge of communication and boundaries for commonly affected joints is essential to perform joint lavage and arthrotomy.

  14. REGULAR EXPRESSION OF DISCOIDIN DOMAIN RECEPTOR 2 IN THE IMPROVED ADJUVANT-INDUCED ANIMAL MODEL FOR RHEUMATOID ARTHRITIS

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Yuan-qiang Zhang; Xin-ping Liu; Li-bo Yao; Lan Sun

    2005-01-01

    Objective To investigate the expression of discoidin domain receptor 2 (DDR2) of fibroblast-like synovial cells in improved adjuvant-induced animal (AIA) model for rheumatoid arthritis (RA) and to provide evidence for DDR2′s antagonist use clinically.Methods AIA was modified by administrating 0.1 mL of complete Freund′s adjuvant (CFA, mixed with 5 mg Bacillus Calmette-Guerin vaccine/mL) into rats′ right hind paws and 0.125 mL tumor necrosis factor-α (2 U/mL) into right ankles and subpatellar fatty tissue. The expression of DDR2 in fibroblast-like synovial cells was assessed using immunohistochemistry,immunofluorescence histochemistry, and in situ hybridization methods. Levels of anti-collagen Ⅱ antibody were measured using enzyme-linked immunosorbent assay.Results Given the terms mentioned above, we found a more practical rat model, apparently decreasing immunization time (average 3-5 days). DDR2 can be detected upon the 15th day of immunization; expression gradually increased with time going on, and reaching a peak 35 days after immunization before gradually decreasing. Serum anti-collagen Ⅱ antibody showed similar expression patterns as DDR2, but reached peak later than DDR2, about 40 days after immunization.Conclusion Regular expression of DDR2 in animal models infers its important role in the pathological process of RA.

  15. Nitric oxide-driven hypoxia initiates synovial angiogenesis, hyperplasia and inflammatory lesions in mice.

    Directory of Open Access Journals (Sweden)

    Fei Bao

    Full Text Available BACKGROUND: Rheumatoid arthritis (RA is an inflammatory articular disease with cartilage and bone damage due to hyperplasic synoviocyte invasion and subsequent matrix protease digestion. Although monoclonal antibodies against tumor necrosis factor alpha (TNFα have been approved for clinical use in patients with RA, desired therapeutic regimens suitable for non-responders are still unavailable because etiological initiators leading to RA remain enigmatic and unidentified. METHODOLOGY/PRINCIPAL FINDINGS: Bacteria-induced arthritis (BIA that simulates collagen-induced arthritis (CIA is developed in mice upon daily live bacterial feeding. The morphological lesions of paw erythema and edema together with the histological alterations of synovial hyperplasia and lymphocytic infiltration emerge as the early-phase manifestations of BIA and CIA. Bacteria- or collagen-mediated global upregulation of pro-inflammatory cytokines is accompanied by the burst of nitric oxide (NO. Elevation of the serum NO level is correlated with decline of the blood oxygen saturation percentage (SpO2, reflecting a hypoxic consequence during development towards arthritis. NO-driven hypoxia is further evident from a positive relationship between NO and lactic acid (LA, an end product from glycolysis. Upregulation of hypoxia inducible factor 1 alpha (HIF-1α and vascular endothelial growth factor (VEGF validates hypoxia-induced angiogenesis in the inflamed synovium of modeling mice. Administration of the NO donor compound sodium nitroprusside (SNP causes articular inflammation by inducing synovial hypoxia. Anti-bacteria by the antibiotic cefotaxime and/or the immunosuppressant rapamycin or artesunate that also inhibits nitric oxide synthase (NOS can abrogate NO production, mitigate hypoxia, and considerably ameliorate or even completely abort synovitis, hence highlighting that NO may serve as an initiator of inflammatory arthritis. CONCLUSIONS/SIGNIFICANCE: Like collagen

  16. SIRT1 overexpression in the rheumatoid arthritis synovium contributes to proinflammatory cytokine production and apoptosis resistance

    NARCIS (Netherlands)

    Niederer, F.; Ospelt, C.; Brentano, F.; Hottiger, M.O.; Gay, R.E.; Gay, S.; Detmar, M.; Kyburz, D.

    2011-01-01

    Objective To analyse the expression of SIRT1 in synovial tissues and cells of patients with rheumatoid arthritis (RA) and to study the function of SIRT1 in inflammation and apoptosis in RA. Methods Levels of SIRT1 expression were analysed in synovial tissues and cells from patients with RA by real-t

  17. Effects of Qubi Zhentong Recipe on the Expressions of IL-1β, IL-8, and VEGF in the Synovial of Rats with Collagen-inducing Arthritis%祛痹镇痛方对胶原诱导性关节炎大鼠滑膜IL-1β、IL-8、VEGF表达的影响

    Institute of Scientific and Technical Information of China (English)

    余建明; 刘喜德; 曲丕盛; 陶凡; 王云卿

    2013-01-01

    目的 研究中药祛痹镇痛方对胶原诱导性关节炎(collagen induced arthritis,CIA)大鼠滑膜白介素-1β(interleukin-1β,IL-1β)、白介素-8(interleukin-8,IL-8)、血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响,探讨祛痹镇痛方治疗CIA的作用机制.方法 选用健康雄性Wistar大鼠,随机分为造模组(50只)及正常对照组(正常组,10只),造模组采用牛Ⅱ型胶原(type Ⅱ collagen of bovine,BCⅡ)乳剂于大鼠尾根部及颈背部多点注射,建立CIA模型.造模成功后,选取30只造模成功大鼠随机分为模型组(10只)、甲氨喋呤(methotrexate,MTX)组(10只)、祛痹镇痛方组(中药组,10只).中药组大鼠按22.9 g/kg剂量灌胃中药祛痹镇痛方,正常组、模型组灌胃等量生理盐水,每日1次,MTX组按 0.78 mg/kg剂量灌胃MTX混悬液,每周1次.给药30天后,运用免疫组化法检测大鼠滑膜IL-1β、IL-8、VEGF水平,并予给药前后进行关节炎指数(arthritis index,AI)评分.结果 与模型组及本组治疗前比较,治疗后中药组和MTX组大鼠AI评分明显降低(P 0.05).结论 降低CIA大鼠滑膜IL-1β、IL-8、VEGF水平可能是中药祛痹镇痛方治疗CIA的作用机制之一.%Objective To research the effects of Qubi Zhentong Recipe (QZR)on the expressions of interleukin-1 β (IL-1 β), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF)in the synovial of rats with collagen-inducing arthritis (CIA), and to discuss its mechanisms of action. Methods Healthy male Wistar rats were recruited and randomly divided into the model group ( n =50)and the normal control group ( n =10). Rats of the model group were injected with type Ⅱ collagen of bovine (BC Ⅱ )emulsion in the tail and nape to establish the CIA model. After successful modeling, 30 successfully modeled rats were selected and randomly divided into three groups ,i.e., the model group (n=10),the QZR group ( n =10) ,and the methotrexate (MTX)group ( n = 10

  18. Construction and Identification ofa cDNA Library of Human Rheumatoid Arthritis Synovial Tissue%人类风湿性关节炎滑膜组织cDNA文库的构建

    Institute of Scientific and Technical Information of China (English)

    闫永毅; 任蕾; 高飞; 卢秀敏; 刘彦虹

    2012-01-01

    Objective:To construct a cDNA library of human synovial tissue of RA and indentify the quality of the library. Methods: Total RNA was extracted and mRNA was purified. mRNA was reversed to first-strand cDNA which was amplified to double-strand cD-NA by long distance PCR. PCR products were digested by proteinase K and Sfi I, and were fractionated by CHROMA SPIN-400 column. The cDN A of length longer than 0.4kb were collected and ligated toλ TriplEx2 vector. The λ phage packaging reaction for the ligated DNA was performed to produce an unamplified library. Thereafter, the unamplified library was titered and the percentage of recombinant clones were detected. In the end, fourty plaques were randomly selected and amplified by PCR using universal primers from vector in order to test the qualify of the obtained library. Results: The titers of unamplifed and amplified libraries were 6.89x106 pfu/mL and 2.63x 109 pfu/mL respectively. The rate of recombinant was 93%. The insert size range from 300 to 1800 bp. Conclusions: A high quality cD-NA library from human synovial tissue of RA was constructed successfully, and it lays solid foundation not only for screening and cloning new special genes associated with the occurrence of RA, but also for gene therapy of it.%目的:构建人类风湿关节炎(RA)滑膜组织cDNA文库.筛查与RA相关的特异基因,为探讨RA的发病机制及基因治疗奠定基础.方法:提取人类风湿关节炎滑膜组织RNA并使用Trizol法纯化mRNA;运用mRNA5'末端的模板转换方法以powerscriptTM逆转录酶进行转录,使用COS Ⅲ/3'PCR引物合成第1链cDNAs;长距离聚合酶链反应(LD-PCR)合成双链cDNA; PCR产物经蛋白酶K水解并纯化后,经SfiI酶切、柱层析洗脱,重组于TripIEx2载体并包装后,测定滴度、重组率、扩增文库,随机挑取40个噬菌斑,用载体克隆位点两端的通用引物进行PCR扩增,以检测所构建cDNA文库的质量.结果:未扩增文库的滴度为6.89× 106pfu/m

  19. Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice.

    Science.gov (United States)

    Fujisawa, K; Asahara, H; Okamoto, K; Aono, H; Hasunuma, T; Kobata, T; Iwakura, Y; Yonehara, S; Sumida, T; Nishioka, K

    1996-07-15

    We have recently demonstrated Fas-mediated apoptosis in the synovium, of patients with rheumatoid arthritis (RA) and suggested that it may be one factor responsible for the regression of RA. To examine whether the induction of apoptosis caused by anti-Fas mAb may play a potential role as a new therapeutic strategy for RA, we investigated the effect of anti-Fas mAb (RK-8) on synovitis in an animal model of RA, the human T cell leukemia virus type I (HTLV-1) tax transgenic mice. We report here that administration of anti-Fas mAb into mice intra-articularly improved the paw swelling and arthritis within 48 h. Immunohistochemical study and in vitro culture studies showed that 35% of synovial fibroblasts, 75% of mononuclear cells, and some of polymorphonuclear leukocytes infiltrating in synovium underwent apoptosis by anti-Fas mAb. In situ nick end labeling analysis and electron microscope analysis clearly showed that many cells in synovium were induced apoptosis by anti-Fas mAb administration. However, local administration of anti-Fas mAb did not produce systemic side effects. Results demonstrated that administration of anti-Fas mAb in arthritic joints of the HTLV-1 tax transgenic mice produced improvement of arthritis. These findings suggest that local administration of anti-Fas mAb may represent a useful therapeutic strategy for proliferative synovitis such as RA.

  20. 血栓素 A2受体通过介导环氧酶2的合成增强类风湿关节炎滑膜细胞的增殖作用%Thromboxane A2 receptor induces proliferation of rheumatoid arthritis synovial cells by up-regulation of cyclooxygenase-2

    Institute of Scientific and Technical Information of China (English)

    储永良; 黄清春; 黄闰月; 晏靖遥; 陈秀敏; 徐侦雄

    2014-01-01

    目的:研究血栓素A2受体(thromboxane A2 receptor, TXA2R)作为环氧酶2(cyclooxygenase-2, COX-2)下游产物对类风湿关节炎(rheumatoid arthritis,RA)滑膜细胞增殖力和COX-2表达的影响。方法:利用细胞增殖与毒性检测试剂盒(MTS)检测TXA2R拮抗剂SQ29548和激动剂U46619对RA关节滑膜细胞MH7A增殖力的影响作用,并用real-time PCR检测它们对COX-2 mRNA表达的影响;利用BrdU细胞增殖检测法观察MH7A细胞在转染COX-2小干扰RNA(small interfering RNA, siRNA)后细胞增殖受抑制的情况及额外施加U46619的可能影响。结果:SQ29548和U46619分别具有抑制和促进MH7A细胞增殖力与COX-2 mRNA表达的作用,且U46619可在一定程度上重建由COX-2 siRNA所抑制的MH7A细胞增殖力。结论:TXA2通过其受体TXA2 R既可控制COX-2的表达,又可介导COX-2的细胞增殖效应,有可能作为RA治疗较为理想的新靶标。%AIM:To examine the effects of thromboxane A 2 receptor ( TXA2 R) , the downstream product of cy-clooxygenase-2 (COX-2), on the proliferative ability and COX-2 expression in rheumatoid arthritis (RA) synovial cells. METHODS:The effects of TXA2 R antagonist SQ29548 and agonist U46619 on the proliferation of RA synovial cell line MH7A were detected by MTS cell proliferation assay , and their effects on COX-2 mRNA expression in MH7A cells were al-so examined by real-time PCR.In addition, the possible effect of U46619 on the proliferation of MH7A cells, when COX-2 was knocked down by siRNA , was determined by BrdU cell proliferation assay .RESULTS:SQ29548 inhibited the cell proliferation and the mRNA level of COX-2 while U46619 enhanced them.Moreover, U46619 reconstitute the proliferative ability of MH7A cells to some extent that inhibited by COX-2 siRNA.CONCLUSION: In RA synovial cells, TXA2R is able to control COX-2 expression, while it also mediates the effects of COX-2, suggesting that TXA2R might be an ideal

  1. Synovial fluid over the centuries

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-09-01

    Full Text Available This review deals with the most meaningful historical topics on the study of synovial fluid, by starting from the Greco- Roman Medicine, up to Paracelsus (1493-1541, who introduced the term “synovia” to name the intra-articular humour. Afterwards, some till now unreported historical sources are recorded, e.g., a short text by the Italian XVIII century physician Giambattista Contoli (“Breve Instruzione sopre il Glutine, ò Colla…, 1699”. Then, in keeping with some recent researches, a brief history of arthrocentesis is outlined, by considering the first procedures, which should have been performed in Mexico, during the precolonial period. Moreover, the first chemical analysis of synovial fluid, as carried out by the French chemist Jean-Louis Margueron (1792, and the first modern study on the synovial membrane by Marie-François-Xavier Bichat (1800 are explained. Finally, some XIX century investigations concerning the synovial pharmacodynamics, in particular an Italian one based on the elimination of certain chemical substances through the synovial membrane, are discussed.

  2. Fungal arthritis and osteomyelitis.

    Science.gov (United States)

    Kohli, Rakhi; Hadley, Susan

    2005-12-01

    Fungal arthritis and osteomyelitis are uncommon diseases and generally present in an indolent fashion. The incidence of fungal bone and joint dis-ease is increasing with an increase in the prevalence of factors predisposing to invasive fungal disease, such as the use of central venous catheters, broad spectrum antibiotics, immunosuppression, and abdominal surgery. Definitive diagnosis relies on bone or synovial culture or biopsy. Successful management has traditionally consisted of amphotericin B in combination with surgical debridement. Given the rarity of this disease, treatment is not well defined, but reports of success with the use of azole antifungal agents, including itraconazole, fluconazole, voriconazole, and posaconazole, are promising.

  3. 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.

  4. 共培养下后交叉韧带成纤维细胞中赖氨酰氧化酶的基因表达**☆%Lysyl oxidase gene expressions in the posterior cruciate ligament fibroblasts co-cultured with synovial cells

    Institute of Scientific and Technical Information of China (English)

    张艳君; 梅虎; 蒋稼欢; 谢静; 尹琳; 陈荣富; 许春明; 王春莉; 宋国立

    2013-01-01

    to improve the healing ability of injured posterior cruciate ligament, we need to find new ways for regeneration and repair of injured posterior cruciate ligament. Previous studies have demonstrated that lysyl oxidases play an important role in the tissue repair mechanism, but the effect of lysyl oxidases from injured posterior cruciate ligament on the process of wound repair remains unclear. OBJECTIVE: To investigate the expressions of lysyl oxidases in the posterior cruciate ligament fibroblasts co-cultured with synovial cel s. METHODS: The fourth passage of posterior cruciate ligament fibroblasts and synovial cel s were placed in 6-wel plates and Transwel , respectively. Two groups were designed as fol ows, posterior cruciate ligament fibroblasts group as control and co-cultured group termed as test group. At 6 hours after co-culture, total RNA was isolated and the expressions of lysyl oxidases in the posterior cruciate ligament fibroblasts were analyzed by semi-quantitative reverse-transcription PCR and quantitative real-time PCR. RESULTS AND CONCLUSION: The results revealed that co-culture contributed to up-regulations of lysyl oxidases compared with the control group, and gene levels were up to 1.1 folds in lysyl oxidase, 1.4 folds in lysyl oxidase-like 1 protein, 1.1 folds in lysyl oxidase-like 2 protein, 1.3 folds in lysyl oxidase-like 3 protein, 1.1 folds in lysyl oxidase-like 4 protein in co-cultured posterior cruciate ligament cel s (P < 0.05). The differential expression of lysyl oxidases in co-cultured posterior cruciate ligament cel s implies that cel-cel interaction and crosstalk are related with posterior cruciate ligament wound healing and have significant potential value and clinical usage for cure of injured posterior cruciate ligament.

  5. IL-26 is overexpressed in rheumatoid arthritis and induces proinflammatory cytokine production and Th17 cell generation.

    Directory of Open Access Journals (Sweden)

    Murielle Corvaisier

    Full Text Available Interleukin-26 (IL-26, a member of the IL-10 cytokine family, induces the production of proinflammatory cytokines by epithelial cells. IL-26 has been also reported overexpressed in Crohn's disease, suggesting that it may be involved in the physiopathology of chronic inflammatory disorders. Here, we have analyzed the expression and role of IL-26 in rheumatoid arthritis (RA, a chronic inflammatory disorder characterized by joint synovial inflammation. We report that the concentrations of IL-26 are higher in the serums of RA patients than of healthy subjects and dramatically elevated in RA synovial fluids compared to RA serums. Immunohistochemistry reveals that synoviolin(+ fibroblast-like synoviocytes and CD68(+ macrophage-like synoviocytes are the main IL-26-producing cells in RA joints. Fibroblast-like synoviocytes from RA patients constitutively produce IL-26 and this production is upregulated by IL-1-beta and IL-17A. We have therefore investigated the role of IL-26 in the inflammatory process. Results show that IL-26 induces the production of the proinflammatory cytokines IL-1-beta, IL-6, and tumor necrosis factor (TNF-alpha by human monocytes and also upregulates the expression of numerous chemokines (mainly CCL20. Interestingly, IL-26-stimulated monocytes selectively promote the generation of RORgamma t(+ Th17 cells, through IL-1-beta secretion by monocytes. More precisely, IL-26-stimulated monocytes switch non-Th17 committed (IL-23R(- or CCR6(- CD161(- CD4(+ memory T cells into Th17 cells. Finally, synovial fluids from RA patients also induce Th17 cell generation and this effect is reduced after IL-26 depletion. These findings show that IL-26 is constitutively produced by RA synoviocytes, induces proinflammatory cytokine secretion by myeloid cells, and favors Th17 cell generation. IL-26 thereby appears as a novel proinflammatory cytokine, located upstream of the proinflammatory cascade, that may constitute a promising target to treat RA and

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  7. Microcirculation of the juvenile knee in chronic arthritis

    DEFF Research Database (Denmark)

    Bünger, Cody; Bülow, J; Tøndevold, E

    1986-01-01

    In order to investigate pathogenetic factors in growth abnormalities of the knee in hemophilic arthropathy and juvenile rheumatoid arthritis, the hemodynamic changes of the knee following chronic synovial inflammation and elevated joint pressure were studied in puppies. Unilateral arthritis was i....... The growth plates formed borders for the extension of these changes. The increased permeability and surface area between blood and bone in arthritis may accelerate the resorption and subsequent destruction of subchondral bone in chronic arthropathies of the juvenile knee.......In order to investigate pathogenetic factors in growth abnormalities of the knee in hemophilic arthropathy and juvenile rheumatoid arthritis, the hemodynamic changes of the knee following chronic synovial inflammation and elevated joint pressure were studied in puppies. Unilateral arthritis...

  8. The diagnosis and treatment of arthritis in horses.

    Science.gov (United States)

    Rose, R J

    1983-01-01

    In this paper on the diagnosis and treatment of arthritis in horses, both degenerative arthritis and septic arthritis are considered. Diagnosis should be made on the combination of clinical examination together with the use of diagnostic aids such as radiology, intra-articular local anaesthesia and synovial fluid analysis. Intra-articular therapy appears to be the most effective in the treatment of degenerative arthritis. Excellent responses to therapy have been reported with corticosteroids, sodium hyaluronate, orgotein and synovial fluid transfer, where joints showed an absence of degenerative changes on radiographs. In septic arthritis, systemic treatment with the appropriate antibiotic, following bacterial culture and sensitivity testing, can produce good results if prompt diagnosis is made.

  9. Update on Therapeutic Approaches for Rheumatoid Arthritis.

    Science.gov (United States)

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

    2016-01-01

    Rheumatoid arthritis is a common chronic inflammatory and destructive arthropathy that consumes considerable personal, social and economic costs. It consists of a syndrome of pain, stiffness and symmetrical inflammation of the synovial membrane (synovitis) of freely moveable joints such as the knee (diarthrodial joints). Although the etiology of rheumatoid arthritis is unclear, the disease is characterized by inflammation of the synovial lining of diarthrodial joints, high synovial proliferation and an influx of inflammatory cells, macrophages and lymphocytes through angiogenic blood vessels. Diseasemodifying antirheumatic drugs slow disease progression and can induce disease remission in some patients. Methotrexate is the first line therapy, but if patients become intolerant to this drug, biologic agents should be used. The development of biological substances for the treatment of rheumatic conditions has been accompanied by ongoing health economic discussions regarding the implementation of these highly effective, but accordingly, highly priced drugs are the standard treatment guidelines of rheumatic diseases. In this way, more efficient strategies have to be identified. Despite numerous reviews in rheumatoid arthritis in the last years, this area is in constant development and updates are an urgent need to incorporate new advances in rheumatoid arthritis research. This review highlights the immunopathogenesis rationale for the current therapeutic strategies in rheumatoid arthritis.

  10. 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.

  11. 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...... or synovial membrane volume, e.g. no systematic errors were found. The inter-MRI variation, evaluated in three knees and three wrists, was higher than by manual segmentation, particularly due to sensitivity to malalignment artefacts. Examination of test objects proved the high accuracy of the general...... methodology for volume determinations (maximal error 6.3%). Preceded by the determination of reproducibility and the optimal threshold at the available MR unit, automated 'threshold' segmentation appears to be acceptable when changes rather than absolute values of synovial membrane volumes are most important...

  12. Fibroblast-like synoviocytes induce calcium mineral formation and deposition.

    Science.gov (United States)

    Sun, Yubo; Mauerhan, David R; Franklin, Atiya M; Zinchenko, Natalia; Norton, Harry James; Hanley, Edward N; Gruber, Helen E

    2014-01-01

    Calcium crystals are present in the synovial fluid of 65%-100% patients with osteoarthritis (OA) and 20%-39% patients with rheumatoid arthritis (RA). This study sought to investigate the role of fibroblast-like synoviocytes (FLSs) in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla) protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s). The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

  13. Fibroblast-Like Synoviocytes Induce Calcium Mineral Formation and Deposition

    Directory of Open Access Journals (Sweden)

    Yubo Sun

    2014-01-01

    Full Text Available Calcium crystals are present in the synovial fluid of 65%–100% patients with osteoarthritis (OA and 20%–39% patients with rheumatoid arthritis (RA. This study sought to investigate the role of fibroblast-like synoviocytes (FLSs in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s. The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

  14. Application of a Novel Diagnostic Rule in the Differential Diagnosis between Acute Gouty Arthritis and Septic Arthritis.

    Science.gov (United States)

    Lee, Kwang-Hoon; Choi, Sang-Tae; Lee, Soo-Kyung; Lee, Joo-Hyun; Yoon, Bo-Young

    2015-06-01

    Septic arthritis and gout are major diseases that should be suspected in patients with acute monoarthritis. These two diseases are clinically similar and often indistinguishable without the help of synovial fluid analysis. Recently, a novel diagnostic rule for gout without synovial fluid analysis was developed and showed relevant performances. This study aimed to determine whether this diagnostic rule could perform well in distinguishing gout from septic arthritis. The diagnostic rule comprises 7 clinical and laboratory variables, each of which is given a specified score. The probability of gout is classified into 3 groups according to the sum of the scores: high (≥ 8), intermediate (> 4 to arthritis (n = 54) based on synovial fluid analysis. The mean sum of scores of acute gout patients was significantly higher than that of those with septic arthritis (8.6 ± 0.2 vs. 3.6 ± 0.32, P arthritis (Eta[η]: 0.776). The prevalence of acute gouty arthritis, as confirmed by the presence of monosodium crystal, was 95.5% (61/64), 57.5% (19/33), and 5.1% (2/39) in high, intermediate and low probability group, respectively. The recently introduced diagnostic rule properly discriminates acute gout from septic arthritis. It may help physicians diagnose gout in cases difficult to be differentiated from septic arthritis.

  15. Synovial Fluid Antioxidant Vitamins and Trace Elements in Clinically Healthy and Arthritic Joints of Dromedary Camels

    Directory of Open Access Journals (Sweden)

    Aliasghar CHALMEH

    2016-01-01

    Full Text Available Forty six male dromedary camels (Camelus dromedarius, 5 to 10 years of age were entered in this study. Before slaughtering, the animals were visually examined for abnormalities in musculoskeletal system. 33 out of 46 camels did not have any clinical articular abnormalities, whereas 13 ones had gross problems such as lameness and swollen tarsal joints. Based on clinical signs and disease history, these animals were suspected to arthritis. After slaughtering, synovial fluid specimens were taken from tarsal joints of all animals, aseptically and concentrations of zinc, copper, selenium, iron and vitamin A, E and C were assayed. Concentrations of selenium and vitamin C in arthritic joints were significantly lower than clinically healthy camels (P<0.05. Zinc concentration of arthritic synovial fluid was significantly higher than normal joints. These data showed that the arthritis could change the synovial fluid vitamins and trace elements in dromedary camels. In conclusion, the results of the current research showed that arthritic joints are in an oxidative stress situation and information regarding the changing patterns of vitamins and trace elements in synovial fluids can be considered as prognostic and diagnostic criteria for articular inflammatory processes.

  16. RELEVANCE OF ARTHROSCOPIC SYNOVIAL BIOPSY IN JOINT DISORDERS - A PROSPECTIVE STUDY

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    Kali Vara Prasad

    2015-10-01

    Full Text Available BACK GROUND : Synovial biopsy is considered as the gold standard in the diagnosis of various joint disorders and synovial diseases. But sometimes the definitive diagnosis is elusive only by doing biopsy then clinical, hematological and x - ray examinations will help. The advantage with arthroscopic synovial biopsy is that it is easy to perform, minimal discomfort to the patient and can be done at intervals if the diagnosis can n ot be made in the first examination. MATERIAL & METHODS : The present study was conducted in the Department of Orthopedics & Traumatology, Osmania General Hospital/ Medical College, Hyderabad. The duration of the study was from Sept 2012 to Sept 2014. CONCLUSIONS : Arthroscopic synovial biopsy is the mainstay in the management of Joint disorders and Synovial diseases. It is patient friendly and repeated procedures can be undertaken when the definitive diagnosis could not be established in the initial attempt, as is common in some cases of Non - specific synovitis, later being diagnosed either as Osteoarthritis or Rheumatoid Arthritis. This is the greatest advantage in using this procedure.

  17. 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.

  18. Candida arthritis in a patient diagnosed with spondyloarthritis

    Directory of Open Access Journals (Sweden)

    Remzi Çevik

    Full Text Available Abstract Candida arthritis is an unusual manifestation that usually affects the knees. A 35-year-old man presented with a 2-month history of pain and swelling in the right knee. Swelling persisted after anti-inflammatory treatment. Peripheric spondyloarthritis was considered, but methotrexate, sulfasalazine, and methylprednisolone did not reduce the swelling. Direct examination of synovial fluid and a culture were positive for Candida albicans. Intravenous and intra-articular amphotericin-B were administered. The arthritis regressed and a culture and direct staining showed negative results. Candida arthritis should be considered in patients with arthritis that is resistant to treatment and prolonged, even if risk factors are absent.

  19. MR imaging of transient synovitis: differentiation from septic arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Yang, W.J.; Im, S.A.; Lim, G.Y.; Chun, H.J.; Jung, N.Y.; Sung, M.S.; Choi, B.G. [Catholic Univ. of Korea, Seoul (Korea). Dept. of Radiology

    2006-11-15

    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.

  20. The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor α expression in the synovium

    Science.gov (United States)

    Wijbrandts, C A; Dijkgraaf, M G W; Kraan, M C; Vinkenoog, M; Smeets, T J; Dinant, H; Vos, K; Lems, W F; Wolbink, G J; Sijpkens, D; Dijkmans, B A C; Tak, P P

    2008-01-01

    Objective: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)α blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFα expression in the synovium before initiation of treatment. Methods: Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as the expression of various cytokines, adhesion molecules and growth factors. Stained sections were evaluated by digital image analysis. Student t tests were used to compare responders (decrease in DAS28 ⩾1.2) with non-responders (decrease in DAS28 <1.2) and multivariable regression was used to identify the independent predictors of clinical response. Results: Synovial tissue analysis confirmed our hypothesis that the baseline level of TNFα expression is a significant predictor of response to TNFα blocking therapy. TNFα expression in the intimal lining layer and synovial sublining were significantly higher in responders than in non-responders (p = 0.047 and p = 0.008, respectively). The numbers of macrophages, macrophage subsets and T cells (all able to produce TNFα) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1β, IL6, IL18, IL10, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was not associated with response to anti-TNFα treatment. Conclusion: The effects of TNFα blockade are in part dependent on synovial TNFα expression and infiltration by TNFα producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanisms. PMID:18055470

  1. 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.

  2. Bone pathology inpsoriatic arthritis

    Directory of Open Access Journals (Sweden)

    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.

  3. Effect of local viral transfer of interleukin 10 gene on a rabbit arthritis model induced by interleukin 1β

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ning; CUI Hua-dong; XUE Hong-xia

    2008-01-01

    Backgroud Interleukin 1β(IL-1 β)is the principal mediator in the pathogenesis of rheumatoid arthdtis.Continuous injection of interleukin 1β(IL-1β)into the knee articular cavities of anamals can induce models that resemble rheumatoid arthritis.The obiective of this study was to evaluate the feasibility of local recombinant retrovirus viral intedeukin 10(rRV-vIL-10)gene transfer treatment of a rabbit model of arthritis induced by IL-1β.Methods An hIL-1β-induced rabbit rheumatoid arthdtis model was established using the MFG-hIL-1β-neo-HIG-82 cell line,which is capable of continuous secretion of hIL-1a.After transfecting the rabbit synovial fibroblast cell line (MFG-hIL-1β-neo-HIG-82)with rRV-vIL-10,G418 was then added to identify the positive clone.The rRV-vIL-10 positive clone was injected into the established rabbit rheumatoid arthritis model through intra-articular injection.Successful gene transfer was determined by reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry.The levels of IL-1β before and after treatment were determined by enzyme-linked immunosorbent assay.Results Retrovirus vector was an effective vector both to synoviocytes in vitro and synovium tissue in vivo as confirmed by RT-PCR and immunohistochemistry.The rabbit arthritis model treated with rRV-vIL-10 showed a dramatic remission of arthritis and a decline in the level of cytokines such as IL-1β.Conclusions Retrovirus-mediated transfection of vIL-10 successfully transferred the gene into rabbit syrnovium ex vivo and was able to suppress intra-articular inflammation response to IL-1β.

  4. Viral arthritis

    Science.gov (United States)

    Infectious arthritis - viral ... Arthritis may be a symptom of many virus-related illnesses. It usually disappears on its own without ... the rubella vaccine, only a few people develop arthritis. No risk factors are known.

  5. Rheumatoid Arthritis

    Science.gov (United States)

    Rheumatoid arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness and loss of function in ... wrist and fingers. More women than men get rheumatoid arthritis. It often starts in middle age and is ...

  6. 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.

  7. Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats.

    Directory of Open Access Journals (Sweden)

    Rita Cascão

    Full Text Available Rheumatoid arthritis (RA is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA.Celastrol was administered to AIA rats both in the early (4 days after disease induction and late (11 days after disease induction phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively.Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects.Our results validate celastrol as a promising compound for the treatment of arthritis.

  8. The inhibitory effect of IFN-γ on protease HTRA1 expression in rheumatoid arthritis.

    Science.gov (United States)

    Hou, Yuzhu; Lin, Haijiang; Zhu, Linnan; Liu, Zhaoting; Hu, Fanlei; Shi, Jianfeng; Yang, Tao; Shi, Xiaoyun; Guo, Huifang; Tan, Xiaotian; Zhang, Lianfeng; Wang, Qiang; Li, Zhanguo; Zhao, Yong

    2014-07-01

    The high temperature requirement A1 (HTRA1) is a potent protease involved in many diseases, including rheumatoid arthritis (RA). However, the regulatory mechanisms that control HTRA1 expression need to be determined. In this study, we demonstrated that IFN-γ significantly inhibited the basal and LPS-induced HTRA1 expression in fibroblasts and macrophages, which are two major cells for HTRA1 production in RA. Importantly, the inhibitory effect of IFN-γ on HTRA1 expression was evidenced in collagen-induced arthritis (CIA) mouse models and in human RA synovial cells. In parallel with the enhanced CIA incidence and pathological changes in IFN-γ-deficient mice, HTRA1 expression in the joint tissues was also increased as determined by real-time PCR and Western blots. IFN-γ deficiency increased the incidence of CIA and the pathological severity in mice. Neutralization of HTRA1 by Ab significantly reversed the enhanced CIA frequency and severity in IFN-γ-deficient mice. Mechanistically, IFN-γ negatively controls HTRA1 expression through activation of p38 MAPK/STAT1 pathway. Dual luciferase reporter assay and chromatin immunoprecipitation analysis showed that STAT1 could directly bind to HTRA1 promoter after IFN-γ stimulation. This study offers new insights into the molecular regulation of HTRA1 expression and its role in RA pathogenesis, which may have significant impact on clinical therapy for RA and possibly other HTRA1-related diseases, including osteoarthritis, age-related macular degeneration, and cancer.

  9. Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens and autologous antigen presenting cells.

    Science.gov (United States)

    Klasen, I S; Melief, M J; Swaak, T J; Severijnen, A J; Hazenberg, M P

    1993-01-01

    The specificity of T cells in the inflamed joints of patients with rheumatoid arthritis (RA) has been the subject of much study. Bacterial antigens are suspect in the aetiology of rheumatic diseases. The responsiveness of the mononuclear cell fraction of peripheral blood and synovial fluid of patients with RA and of patients with rheumatic diseases other than RA to bacterial antigens such as cell wall fragments of the anaerobic intestinal flora, cell wall fragments of Streptococcus pyogenes, intestinal flora derived peptidoglycan polysaccharide complexes, the 65 kilodalton protein of Mycobacterium tuberculosis, and muramyldipeptide was investigated. No significant difference in response was found to all these bacterial antigens in the synovial fluid of patients with RA compared with the responses in patients with other rheumatic diseases. The highest responsiveness in the synovial fluid of the patients with RA was to the streptococcal cell wall fragments and to the 65 kilodalton protein. Higher responses to several bacterial antigens in the synovial fluid of patients with RA were found compared with peripheral blood from the same patient group. The antigen presenting cell population of the synovial fluid in patients with RA and the patients with other rheumatic diseases was found to be stimulatory for autologous peripheral blood T cells even in the absence of antigen. This suggests an important role for the synovial antigen presenting cell in the aetiology of inflammatory joint diseases. PMID:8447692

  10. Galectin-3: A key player in arthritis.

    Science.gov (United States)

    Hu, Yong; Yéléhé-Okouma, Mélissa; Ea, Hang-Korng; Jouzeau, Jean-Yves; Reboul, Pascal

    2017-01-01

    Arthritis is more and more considered as the leading reason for the disability in the world, particularly regarding its main entities, rheumatoid arthritis and osteoarthritis. The common feature of arthritis is inflammation, which is mainly supported by synovitis (synovial inflammation), although the immune system plays a primary role in rheumatoid arthritis and a secondary one in osteoarthritis. During the inflammatory phase of arthritis, many pro-inflammatory cytokines and mediators are secreted by infiltrating immune and resident joint cells, which are responsible for cartilage degradation and excessive bone remodeling. Amongst them, a β-galactoside-binding lectin, galectin-3, has been reported to be highly expressed and secreted by inflamed synovium of rheumatoid arthritis and osteoarthritis patients. Furthermore, galectin-3 has been demonstrated to induce joint swelling and osteoarthritis-like lesions after intra-articular injection in laboratory animals. However, the mechanisms underlying its pathophysiological role in arthritis have not been fully elucidated. This review deals with the characterization of arthritis features and galectin-3 and summarizes our current knowledge of the contribution of galectin-3 to joint tissue lesions in arthritis.

  11. The Future of Rheumatoid Arthritis and Hand Surgery - Combining Evolutionary Pharmacology and Surgical Technique

    OpenAIRE

    M, Malahias; H, Gardner; S, Hindocha; A, Juma; Khan, W

    2012-01-01

    Rheumatoid arthritis is a systemic autoimmune disease of uncertain aetiology, which is characterized primarily by synovial inflammation with secondary skeletal destructions. Rheumatoid Arthritis is diagnosed by the presence of four of the seven diagnostic criteria, defined by The American College of Rheumatology. Approximately half a million adults in the United Kingdom suffer from rheumatoid arthritis with an age prevalence between the second and fourth decades of life; annually approximatel...

  12. Synovial fluid cytology in experimental acute canine monocytic ehrlichiosis (Ehrlichia canis).

    Science.gov (United States)

    Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Petanides, Theodoros; Tsafas, Konstantinos; Harrus, Shimon; Mylonakis, Mathios E

    2015-05-15

    Evidence-based information of a cause-and-effect relationship between Ehrlichia canis infection and polyarthritis in naturally- or experimentally-infected dogs is currently lacking. The aim of this prospective study was to investigate whether synovial fluid cytological evidence of arthritis could be documented in dogs with acute monocytic ehrlichiosis. Direct synovial fluid cytology smears from eight Beagle dogs experimentally infected with E. canis were examined prior to, and on 21, 35 and 63 days post-inoculation. The cytological variables assessed included cellularity, percentages of mononuclear cells and neutrophils, macrophage reactivity and evidence of E. canis morulae. The median cellularity and percentages of mononuclear cells and neutrophils prior to inoculation did not differ when compared to post-inoculation cytological evaluation. Increased cellularity, E. canis morulae or cytological evidence of arthritis or macrophage reactivity were not observed throughout the course of the study. In the present study, no cytological evidence of arthritis was found in dogs with experimental acute canine monocytic ehrlichiosis, suggesting that E. canis infection should be considered a rather uncommon cause of arthritis in dogs.

  13. 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 pathogenesi

  14. Sphingolipids in human synovial fluid--a lipidomic study.

    Directory of Open Access Journals (Sweden)

    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.

  15. Juvenile Arthritis

    Science.gov (United States)

    Juvenile arthritis (JA) is arthritis that happens in children. It causes joint swelling, pain, stiffness, and loss of motion. It can affect any joint, but ... of JA that children get is juvenile idiopathic arthritis. There are several other forms of arthritis affecting ...

  16. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin

    NARCIS (Netherlands)

    Vossenaar, E.R.; Despres, N.; Lapointe, E.; Heijden, A.G. van der; Lora, M.; Senshu, T.; Venrooij, W.J.W. van; Menard, H.A.

    2004-01-01

    Antibodies directed to the Sa antigen are highly specific for rheumatoid arthritis ( RA) and can be detected in approximately 40% of RA sera. The antigen, a doublet of protein bands of about 50 kDa, is present in placenta and in RA synovial tissue. Although it has been stated that the Sa antigen is

  17. 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...

  18. MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis.

    Science.gov (United States)

    Chen, Ying; Xian, Pei-Feng; Yang, Lu; Wang, Sheng-Xu

    2016-01-01

    MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway.

  19. Resveratrol inhibits TNF-α-induced IL-1β, MMP-3 production in human rheumatoid arthritis fibroblast-like synoviocytes via modulation of PI3kinase/Akt pathway.

    Science.gov (United States)

    Tian, Jing; Chen, Jin-wei; Gao, Jie-sheng; Li, Len; Xie, Xi

    2013-07-01

    Resveratrol (trans-3,4'-trihydroxystilbene), a natural phytoalexin, possesses anti-inflammatory, anti-proliferative, and immunomodulatory properties and has the potential for treating inflammatory disorders. The present study was designed to investigate the effects of resveratrol on TNF-α-induced inflammatory cytokines production of IL-1β and MMP3 in Rheumatoid arthritis (RA) Fibroblast-like synoviocytes (FLS) and further to explore the role of PI3K/Akt signaling pathway by which resveratrol modulates those cytokines production. The levels of IL-1β, MMP-3 in cultural supernatants among groups were measured by enzyme-linked immunosorbent assay. Messenger RNA expression of IL-1β and MMP-3 in RA FLS was analyzed using a reverse transcription-polymerase chain reaction. Western blot analysis was used to detect proteins expression in RA FLS intervened by resveratrol. Resveratrol inhibited both mRNA and proteins expressions of IL-1β and MMP-3 on RA FLS in a dose-dependent manner. Resveratrol also decreased significantly the expression of phosphorylated Akt dose dependently. Activation of PI3K/Akt signaling pathway exists in TNF-α-induced production of IL-1β and MMP3 on RA FLS, which is hampered by PI3K inhibitor LY294002. Immunofluorescence staining showed that TNF-α alone increased the production of P-Akt, whereas LY294002 and 50 μM resveratrol suppressed the TNF-α-stimulated expression of P-Akt. Resveratrol attenuates TNF-α-induced production of IL-1β and MMP-3 via inhibition of PI3K-Akt signaling pathway in RA FLS, suggesting that resveratrol plays an anti-inflammatory role and might have beneficial effects in preventing and treating RA.

  20. T cell migration in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Mario eMellado

    2015-07-01

    Full Text Available Rheumatoid arthritis (RA is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response.In this review we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies.

  1. Cytokines in rheumatoid arthritis and osteoarthrosis

    Directory of Open Access Journals (Sweden)

    Petrović-Rackov Ljiljana

    2005-01-01

    Full Text Available The aim of this research was to determine the clinical significance of tumor necrosis factor-alpha (TNF-alpha, IL-12, IL-15 and IL-18 in evaluation of the activity of rheumatoid arthritis. Cytokine concentrations in serum samples and synovial fluid were measured by immnnoenzymatic methods using kits for human interleukins and the Disease Activity Score 28 in 64 patients with active disease. The control group consisted of 25 subjects with arthritis of the knee and osteoarthrosis. Patients with rheumatoid arthritis have significantly high (p<0.01 concentrations of examined cytokines in relation to patients with osteoarthritis. By comparing concentrations in 30 patients with high, 14 patients with moderate and 20 patients with mild activity of rheumatoid arthritis, it was established that patients with high degree of disease activity have significantly high (p<0.01; p<0.05 concentrations of examined cytokines in the blood and synovial fluid in relation to patients with moderate and mild disease. We have concluded that cytokine concentrations are good indicators of the degree of rheumatoid arthritis activity. This research is a contribution to understanding the insufficiently known pathogenetic mechanisms of cytokines, especially IL-18, in active disease. .

  2. The relative composition of the inflammatory infiltrate as an additional tool for synovial tissue classification.

    Directory of Open Access Journals (Sweden)

    Cristina Della Beffa

    Full Text Available OBJECTIVES: Traditionally, differences in absolute numbers of cells expressing a certain marker (e.g., positive staining cells per mm² have been used in immunohistological synovial tissue classification. We have begun to evaluate the relative composition of the inflammatory infiltrates, i.e. percentages of inflammatory cell types in inflammatory infiltrates, as an alternate classification tool that may potentially improve tissue diagnostics, subgrouping in clinical trials, and understanding of pathogenesis of inflammatory and noninflammatory arthropathies. METHODS: Synovial tissue specimens (normal synovium, n=15; orthopedic arthropathies, n=6; osteoarthritis, n=26; early undifferentiated arthritis, n=10; rheumatoid arthritis, n=26; chronic septic arthritis, n=11 were stained for CD15, CD68, CD3, CD20, and CD38. Densities of cells expressing a given marker were determined in the superficial subintima. Binary and multicategory receiver operating characteristic (ROC analysis and naïve Bayes classifier were used to compare the abilities of (1 the absolute densities of cells expressing a given marker (absolute method with (2 the percentages of these cells in the inflammatory cell population (relative method to differentiate among the six tissue classes. RESULTS: The inflammatory infiltrates in normal synovium and the orthopedic arthropathies consisted almost exclusively of CD68+ and CD3+ cells. Notable fractions of CD20+ and CD38+ cells appeared in a subset of osteoarthritis samples, and increased further in early, rheumatoid and chronic septic arthritis. ROC analyses and naïve Bayes classifier ranked the absolute method above the relative method in terms of overall discriminatory ability. The relative method became slightly superior when the samples were also stratified according to the total number of inflammatory cells/mm². CONCLUSIONS: This exploratory investigation featuring a variety of joint disorders revealed that measuring the relative

  3. The Relative Composition of the Inflammatory Infiltrate as an Additional Tool for Synovial Tissue Classification

    Science.gov (United States)

    Della Beffa, Cristina; Slansky, Elisabeth; Pommerenke, Claudia; Klawonn, Frank; Li, Jialiang; Dai, Lie; Schumacher, H. Ralph; Pessler, Frank

    2013-01-01

    Objectives Traditionally, differences in absolute numbers of cells expressing a certain marker (e.g., positive staining cells per mm2) have been used in immunohistological synovial tissue classification. We have begun to evaluate the relative composition of the inflammatory infiltrates, i.e. percentages of inflammatory cell types in inflammatory infiltrates, as an alternate classification tool that may potentially improve tissue diagnostics, subgrouping in clinical trials, and understanding of pathogenesis of inflammatory and noninflammatory arthropathies. Methods Synovial tissue specimens (normal synovium, n=15; orthopedic arthropathies, n=6; osteoarthritis, n=26; early undifferentiated arthritis, n=10; rheumatoid arthritis, n=26; chronic septic arthritis, n=11) were stained for CD15, CD68, CD3, CD20, and CD38. Densities of cells expressing a given marker were determined in the superficial subintima. Binary and multicategory receiver operating characteristic (ROC) analysis and naïve Bayes classifier were used to compare the abilities of (1) the absolute densities of cells expressing a given marker (absolute method) with (2) the percentages of these cells in the inflammatory cell population (relative method) to differentiate among the six tissue classes. Results The inflammatory infiltrates in normal synovium and the orthopedic arthropathies consisted almost exclusively of CD68+ and CD3+ cells. Notable fractions of CD20+ and CD38+ cells appeared in a subset of osteoarthritis samples, and increased further in early, rheumatoid and chronic septic arthritis. ROC analyses and naïve Bayes classifier ranked the absolute method above the relative method in terms of overall discriminatory ability. The relative method became slightly superior when the samples were also stratified according to the total number of inflammatory cells/mm2. Conclusions This exploratory investigation featuring a variety of joint disorders revealed that measuring the relative proportions of

  4. 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...

  5. Rheumatoid synovial inflammation: pixel-by-pixel dynamic contrast-enhanced MR imaging time-intensity curve shape analysis--a feasibility study

    NARCIS (Netherlands)

    C. van der Leij; M.G.H. van de Sande; C. Lavini; P.P. Tak; M. Maas

    2009-01-01

    PURPOSE: To analyze the distribution of different shapes of time-intensity curves (TICs) in synovial tissue of patients with rheumatoid arthritis (RA) and to compare relative numbers of TIC shapes between patients with RA and healthy control subjects. MATERIALS AND METHODS: This prospective study wa

  6. Therapeutical approach to rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Paraskevi Gourni

    2008-10-01

    Full Text Available Rheumatoid arthritis (RA is a chronic disease characterized by inflammation of the synovial joints, and loss of the function leading to disability. The ultimate goal in managing RA is to prevent joint damage and to maintain functional ability. Although, οver the past decade, major advances have been made in our understanding of the factors that are crucial in regulating this disease, still the managment of the disease remains difficult.Aim : Τhe aim of the present study was the evaluation of the therapeutical approch on rheumatoid arthritis. The method οf this study included bibliography research from both the review and the research literature which referred to the relation between therapy and rheumatoid arthritis.Results : The majority of research studies showed thatthe main therapy on rheumatoid arthritis included medication therapy, modification of everyday living ensuring rest, physical exercise and finally surgical procedure. Individuals suffering from rheumatoid arthritis, apart from physical problems usually cope with mental disorders, that exert a negative indluence on their quality of life.Conclusively :Information and early screening of high risk may decrease the long-term consequnences on health. Monitoring from a group of specialists should serve as a cornerstone when planning a program of intervention.

  7. Nitrated type III collagen as a biological marker of nitric oxide-mediated synovial tissue metabolism in osteoarthritis

    DEFF Research Database (Denmark)

    Richardot, P; Charni-Ben Tabassi, N; Toh, L

    2009-01-01

    OBJECTIVES: Nitric oxide (NO) is a major mediator of joint tissue inflammation and damage in osteoarthritis (OA) and mediates the nitration of tyrosine (Y*) residues in proteins. We investigated the nitration of type III collagen, a major constituent of synovial membrane, in knee OA. METHODS...... in healthy controls and significantly correlated with C-reactive protein values (r=0.40, Pcollagen N-telopeptide is increased in the synovial tissue of patients with knee OA. Measurements of serum IIINys level may be useful for the clinical......: A polyclonal antibody directed against the nitrated QY*DSY*DVKSG sequence from type III collagen N-telopeptide was generated. Synovial tissues from patients with knee OA (n=4) and rheumatoid arthritis (RA, n=4) were analyzed by immunohistochemistry for IIINys. Serum IIINys levels were measured by enzyme...

  8. Influence of estrogen cycle on temporomandibular joint synovial membrane in rat with deviated mandible.

    Science.gov (United States)

    Kishimoto, Giovanna; Hosomichi, Jun; Muramoto, Takeshi; Kanno, Zuisei; Soma, Kunimichi

    2007-03-01

    Temporomandibular disorders (TMD) are known to be more prevalent and severe in women than in men, especially in those who are in their reproductive age. In those patients reproductive hormones may play a vital role in the host adaptive capacity of the temporomandibular joint (TMJ). In order to clarify the relationship between TMD prevalence and estrogen cycle, a mandible deviated animal model was carried out, and the expression of inducible nitric oxide synthase (iNOS), an essential enzyme in the pathogenesis of inflammatory arthritis, was investigated in the rat's synovial tissue. An appliance was attached to the rat's incisors to produce a lateral deviation of the mandible during the metestrus phase, and the animals were sacrificed in the proestrus and estrus phase, when the estrogen was at the highest and lowest level, respectively. Immunostaining was then performed for 2 consecutive estrous cycles to demonstrate iNOS expression in the synovial membrane of the TMJ. The immunoreactivity for iNOS was more intense in the synovial membrane on the contralateral side in the proestrus phase (estrogen peak phase). These observations suggest that iNOS expression in the synovial membrane with mandibular deviation may be exacerbated in the presence of estrogen.

  9. Isolated polyarticular septic arthritis: an atypical presentation of meningococcal infection.

    Science.gov (United States)

    McCulloch, Michael; Brooks, Heather; Kalantarinia, Kambiz

    2008-04-01

    We are presenting a case of a 19-year-old college student with sudden-onset, asymmetric polyarticular arthritis with Neisseria meningitidis 10 days after an acute upper respiratory infection consisting of fevers, chills, pharyngitis, and productive cough. Primary meningococcal septic arthritis is a rare entity. A majority of these cases present in a monoarticular fashion. The synovial fluid findings, although compatible with inflammatory arthritis, are not typical of septic arthritis. This entity, although rare, should be considered in the differential diagnosis of septic arthritis of large joints, especially since N. meningitiditis does not grow well on routine culture media. A literature review on the diagnosis, treatment, and prevention of primary meningococcal septic arthritis is presented.

  10. Synovial Sarcoma in the Rectovesical Space: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Min Chul; Cho, Bum Sang; Han, Gi Seok; Park, Kil Sun; Kim, Sung Jin; Cha, Sang Hoon; Lee, Seung Young; Kang, MIn Ho [Dept. of Radiology, Chungbuk National University Hospital, Chunju (Korea, Republic of); Lee, Ok Jun [Dept. of Pathology, Chungbuk National University Hospital, Chunju (Korea, Republic of)

    2011-08-15

    Synovial sarcoma is an uncommon soft tissue malignancy usually arising in the extremities of young adults. Synovial sarcomas at unusual anatomic locations have been reported; however, to the best of our knowledge, there are no reports on primary synovial sarcoma in the rectovesical space. Here, we describe the radiologic findings of primary synovial sarcoma in the rectovesical space and review relevant literature.

  11. Kinesiotherapy for quality of life, pain and muscle strength of rheumatoid arthritis and systemic lupus erythematosus patient. Case report

    OpenAIRE

    Myra,Rafaela Simon; DeMarco,Mariângela; Zanin, Caroline; Wibelinger, Lia Mara

    2015-01-01

    ABSTRACT BACKGROUND AND OBJECTIVES: Rheumatoid arthritis is an inflammatory, chronic and progressive disease. It impairs joint synovial membranes and may induce bone and cartilage destruction. Many diseases may follow rheumatoid arthritis, including systemic lupus erythematosus, an inflammatory, chronic autoimmune disease with multisystemic manifestations, with periods of remission and exacerbation. This study aimed at reporting kinesiotherapy intervention for quality of life, pain and muscle...

  12. SYNOVIAL GIANT CELL TUMOR OF THE KNEE.

    Science.gov (United States)

    Abdalla, Rene Jorge; Cohen, Moisés; Nóbrega, Jezimar; Forgas, Andrea

    2009-01-01

    Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection.

  13. [In-vitro study on dissection of inflamed synovial tissue by hydro-jet cutting].

    Science.gov (United States)

    Wagner, K-H; Tarner, I H; Lange, U

    2012-10-01

    Surgical synovectomy is a useful therapeutic option for rheumatoid arthritis patients with ongoing active synovitis despite optimal medical therapy. The present experimental study evaluated the novel, minimally invasive surgical technique of hydro-jet cutting in vitro using synovial biopsies. Depending on the selected water pressure (30-100 bar) it is possible to achieve precise and selective dissection of the synovial membrane. It was found that application of a water jet at 60 bar for 15 s is ideal for dissecting the stratum synoviale from the stratum fibrosum without any alteration of the joint capsule. This finding was confirmed by histological analyses. This novel and precise dissection technique promises to be an excellent alternative to the established techniques of synovectomy in the near future.

  14. Osteochondroma and secondary synovial osteochondromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Peh, W.C.G. [Dept. of Diagnostic Radiology, Univ. of Hong Kong (Hong Kong); Shek, T.W.H. [Department of Pathology, Univ. of Hong Kong (Hong Kong); Davies, A.M. [Department of Diagnostic Radiology, Royal Orthopaedic Hospital, Birmingham (United Kingdom); Wong, J.W.K.; Chien, E.P. [Department of Orthopaedic Surgery, Univ. of Hong Kong (Hong Kong)

    1999-03-01

    Secondary synovial osteochondromatosis (SOC) is a rare disorder caused by a variety of joint disorders. Two unusual cases of secondary SOC are presented. The first patient is a 43-year-old man with extensive SOC developing within a bursa surrounding an osteochondroma of the pubic bone. The second patient is a 23-year-old man who developed florid and progressive SOC of his hip joint following excision of a femoral neck osteochondroma. SOC recurred despite three excisions over a 15-month period. Imaging was useful in pre-operative diagnosis of bursal SOC in the first patient and in detecting multiple recurrences in the second patient. Both cases illustrate prominent SOC developing secondary to osteochondroma. The different hypotheses regarding bursal and secondary SOC are reviewed. (orig.) With 7 figs., 19 refs.

  15. Primary synovial sarcoma of lung

    Directory of Open Access Journals (Sweden)

    Devleena

    2014-01-01

    Full Text Available A synovial sarcoma (SS is a rare form of cancer which usually occurs near the joints of the arm, neck, or leg, but has been documented in most human tissues and organs, including the brain, prostate, and heart. Primary pulmonary SS is an extremely rare tumor. We report a case of primary SS of lung who presented with severe chest pain and a large right lung mass with right-sided pleural effusion in computed tomography (CT scan of thorax. The diagnosis was made on the basis of CT-guided core biopsy and immunohistochemistry. On immunohistochemistry, tumor cell expressed epithelial membrane antigen, bcl 2, Vimentin and smooth muscle actin and were immunonegative for S100 and cytokeratin. So, the final diagnosis was primary SS.

  16. 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.

  17. Detection and their clinical significance of cytokines levels in serum and synovial fluid from patients with rheumatoid arthritis%类风湿关节炎患者血清和关节液细胞因子水平的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    成胜权; 张国成; 李琦; 刘雪松

    2001-01-01

    目的探讨幼年类风湿关节炎 (JRA)及类风湿关节炎 (RA)患者 IL-6、 IL-8、 sIL-2R和 TNF-α等细胞因子 (CK)水平的变化 ,及其与风湿活动的传统指标血沉 (ESR)和 C-反应蛋白 (CRP)的相关性。方法采用夹心 ELISA法,对 30例 JRA 和 34例 RA患者的血清中, 4例 JRA、 7例 RA、 6例骨性关节炎 (OA)和 9例半月板损伤 (MT)患者的关节液中 IL-6、 IL-8、 sIL-2R和 TNF-α的水平进行检测。结果① 30例 JRA 、 34例 RA患者血清 IL-6和 sIL-2R的水平与对照组相差非常显著 (P〈 0.01); 30例 JRA 患者血清 IL-8水平与对照组比较相差显著 (P〈 0.05)。② JRA全身型、少关节型患者血清 IL-8、 sIL-2R的水平和 JRA多关节型患者血清 IL-6的水平与对照组相差非常显著 (P〈 0.01)。③ 4例 JRA及 7例 RA患者关节液 sIL-2R的水平和 RA患者关节液的 IL-6水平与对照组相差显著 (P〈 0.05)。④ JRA患者血清 IL-6和 sIL-2R的水平与 ESR和 CRP的变化呈明显的相关关系 (r值分别为 0.532和 0.621)。结论① IL-6、 sIL-2R的水平与 JRA、 RA病的活动性有关,是类风湿活动性的主要指标。② sIL-2R 不仅参与 JRA和 RA的全身病理损伤 ,而且是引起关节局部损伤的主要 CK,IL-6也参与 JRA 关节局部的病理损伤 ,在 RA关节局部损伤似乎更为重要。③ IL-8主要参与 JRA的全身病理损伤 ,对关节局部病理损伤似乎并不重要。%Aim To study cytokine(CK) changes of IL-6,IL-8,sIL-2R and TNF-a levels in sera from patients with juvenile rheumatoid arthritis(JRA) and rheumatoid arthritis(RA) and its correlation with the conventional inflammation indexes,erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP). Methods Levels of IL-6,IL-8,sIL-2R and TNF-a in serum from 30 JRA patients and 34 RA patients,in the synovial fluid (SF)from 4 JRA patients,7 RA patients,6 osteoarthritis(OA) patients and 9 meniscitis(MT) patients were detected by sandwich ELISA

  18. 脊柱关节炎患者膝关节积液中单核巨噬细胞未折叠蛋白反应相关基因表达及其意义%The expression and significance of unfolded protein response-related gene in synovial fluid macrophages in patients with spondyloarthritis and other arthritis

    Institute of Scientific and Technical Information of China (English)

    李凌; 朱剑; 黄烽

    2013-01-01

    目的 探讨脊柱关节炎(SpA)患者膝关节积液中单核巨噬细胞未折叠蛋白反应相关基因表达及其意义.方法 选有明确的膝关节受累、并伴有明显的关节腔积液的SpA患者18例、类风湿关节炎(RA)患者12例、骨关节炎(OA)患者6例,以磁珠分选法分离膝关节积液中单核巨噬细胞,实时定量聚合酶链反应(PCR)检测UPR相关分子编码基因免疫球蛋白结合蛋白(BiP)、热休克蛋白94(GRP94)、C/EBP同源蛋白(CHOP)、生长停滞及DNA损伤诱导蛋白34(GADD34)、X盒结合蛋白1(XBP-1)、内质网DnaJ同系物4(ERdj4) mRNA表达.结果 SpA、RA、OA患者膝关节积液中单核巨噬细胞BiP mRNA[(6.06±2.08)×10-2,(5.41±1.97)×10-2,(1.11 ±0.72) ×10-2] 、GRP94mRNA[11.80(7.30 ~38.40) ×10-3,9.01(4.15~24.40) ×10-3,1.27(1.02~4.18) ×10-3]、XBP1mRNA[(12.70 ±5.20)×10-3,(11.00±4.20)×10-3,(4.14±2.56)×10-3]、GADD34 mRNA[7.30(5.56~15.40) ×10-3,21.30(12.20 ~27.60)×10-3,19.80(5.79 ~30.30)×10-3]表达差异有统计学意义(P<0.01),ERdj4、CHOP mRNA表达差异无统计学意义(P>0.05).SpA HLA-B27阳性者与阴性者间BiP、GRP94、XBP1、ERdj4、CHOP、GADD34 mRNA表达差异无统计学意义(P>0.05).结论 UPR现象与SpA发病机制有一定的相关性,但HLA-B27如何参与UPR以及其所发挥的作用还需进一步深入研究.%Objective To investigate whether unfolded protein response (UPR) plays a role in the pathogenesis of spondyloarthritis (SpA),and to assess UPR-related gene expression in SpA and other arthritis patients.Methods Eighteen patients with SpA,12 with rheumatoid arthritis (RA) and 6 with osteoarthritis (OA) were recruited.Macrophages were isolated from synovial fluid samples by immunomagnetic separation.The expression of UPR-regulated genes,including binding immunoglobulin protein (BiP),glucose-regulated protein 94 (GRP94),C/EBP homologous protein (CHOP),growth arrested and DNA damage-inducible 34 (GADD34),X-box binding protein 1

  19. MR imaging findings of acute gouty arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gyung Kyu [Hallym University College of Medicine, Chuncheon (Korea, Republic of); Lee, Jee Young [Dankook University College of Medicine, Cheonan (Korea, Republic of); Suh, Jin Suck [Yonsei University College of Medicine, Seoul (Korea, Republic of)] (and others)

    2006-08-15

    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

  20. Snapping elbow caused by hypertrophic synovial plica in the radiohumeral joint: a report of three cases and review of literature.

    Science.gov (United States)

    Steinert, Andre F; Goebel, Sascha; Rucker, Alexander; Barthel, Thomas

    2010-03-01

    The snapping elbow caused by hypertrophic synovial radiohumeral plica is a rare form of lateral elbow impingement. In this article we report on hypertrophic radiohumeral synovial folds in three male patients, aged 54, 65 and 27 years. All three patients suffered isolated lateral elbow pain, painful snapping and unsuccessful conservative treatment over at least 5 months (range 5-9 months, mean 7.7 months) prior to surgical treatment. None of the patients had lateral epicondylitis, instability, osteochondrosis dissecans, loose bodies, arthritis or neurological disorders. Upon clinical examination the range of motion in the respective painful elbows was found to be normal in all three cases, but a painful snapping occurred between 80 degrees and 100 degrees of flexion with the forearm in pronation. While there were no pathologic findings in standard radiographs, magnetic resonance imaging (MRI) revealed hypertrophic synovial plicae in the radiohumeral joints associated with effusion in each of the diseased elbows. Arthroscopic examinations confirmed the presence of a hypertrophic synovial plica in all three radiocapitellar joints, and revealed a transient interposition and compression of the folds in the articulation from extension until 90 degrees -100 degrees elbow flexion, with replacement beyond 90 degrees elbow flexion with a visible jump. Surgical management in all three cases comprised arthroscopic diagnosis confirmation and removal of the synovial plicae, leading to excellent outcomes at 6-12 months follow-up.

  1. Gonococcal arthritis

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000453.htm Gonococcal arthritis To use the sharing features on this page, please enable JavaScript. Gonococcal arthritis is inflammation of a joint due to a ...

  2. Infectious Arthritis

    Science.gov (United States)

    Most kinds of arthritis cause pain and swelling in your joints. Joints are places where two bones meet, such as your elbow or knee. Infectious arthritis is an infection in the joint. The infection ...

  3. Psoriatic Arthritis

    Science.gov (United States)

    ... your body. Some people with psoriasis have psoriatic arthritis. It causes pain, stiffness, and swelling of the ... physical exam and imaging tests to diagnose psoriatic arthritis. There is no cure, but medicines can help ...

  4. Fungal arthritis

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000444.htm Fungal arthritis To use the sharing features on this page, please enable JavaScript. Fungal arthritis is swelling and irritation (inflammation) of a joint ...

  5. Sporotrichal arthritis.

    OpenAIRE

    1991-01-01

    Sporotrichal arthritis is a rare disease entity. Diagnosis is often difficult and delayed. Presentation may be either monoarticular or polyarticular. A case of polyarticular sporotrichal arthritis which exemplifies these problems is reported.

  6. Psoriatic Arthritis

    Science.gov (United States)

    ... Call for Letters of Interest Call for Topics Axial Spondyloarthritis Glucocorticoid-Induced Osteoporosis Gout Juvenile Idiopathic Arthritis ... be affected. Psoriatic arthritis in the spine, called spondylitis , causes stiffness in the back or neck, and ...

  7. Synovial chondromatosis of the shoulder: imaging findings

    Directory of Open Access Journals (Sweden)

    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.

  8. Matrix metalloproteinase protein expression profiles cannot distinguish between normal and early osteoarthritic synovial fluid

    Directory of Open Access Journals (Sweden)

    Heard Bryan J

    2012-07-01

    Full Text Available Abstract Background Osteoarthritis (OA and Rheumatoid arthritis (RA are diseases which result in the degeneration of the joint surface articular cartilage. Matrix Metalloproteinases (MMPs are enzymes that aid in the natural remodelling of tissues throughout the body including cartilage. However, some MMPs have been implicated in the progression of OA and RA as their expression levels and activation states can change dramatically with the onset of disease. Yet, it remains unknown if normal and arthritic joints demonstrate unique MMPs expression profiles, and if so, can the MMP expression profile be used to identify patients with early OA. In this study, the synovial fluid protein expression levels for MMPs 1, 2, 3, 7, 8, 9, 12 & 13, as well as those for the Tissue Inhibitors of MMPs (TIMPs 1, 2, 3, & 4 were examined in highly characterized normal knee joints, and knee joints with clinically diagnosed OA (early and advanced or RA. The purpose of this study was to determine if normal, OA, and RA patients exhibit unique expression profiles for a sub-set of MMPs, and if early OA patients have a unique MMP expression profile that could be used as an early diagnostic marker. Methods Synovial fluid was aspirated from stringently characterized normal knee joints, and in joints diagnosed with either OA (early and advanced or RA. Multiplexing technology was employed to quantify protein expression levels for 8 MMPs and 4 TIMPs in the synovial fluid of 12 patients with early OA, 17 patients diagnosed with advanced OA, 15 with RA and 25 normal knee joints. Principle component analysis (PCA was used to reveal which MMPs were most influential in the distinction between treatment groups. K – means clustering was used to verify the visual grouping of subjects via PCA. Results Significant differences in the expression levels of MMPs and TIMPs were observed between normal and arthritic synovial fluids (with the exception of MMP 12. PCA demonstrated that MMPs 2, 8

  9. 幼年特发性关节炎白介素6、γ干扰素诱导蛋白10和白介素17的表达及意义%Expression and significance of interleukin-6, interferon-inducible protein-10 and interleukin-17 in serum and synovial fluid of patients with juvenile idiopathic arthritis

    Institute of Scientific and Technical Information of China (English)

    李瑞娟; 唐雪梅; 刘玮; 周娟; 安云飞; 秦仕英; 邹宗毅

    2013-01-01

    目的 研究幼年特发性关节炎(JIA)患儿外周血及关节液中白介素6(IL-6)、γ干扰素诱导蛋白10(IP-10)及白介素17(IL-17)的表达差异.方法 收集JIA患儿血清27例[其中全身型JIA (sJIA) 13例、多关节型JIA(pJIA) 14例]及关节液18例;疑诊sJIA患儿血清19例.另收集健康体检儿童血清28例作为对照.采用酶联免疫吸附法检测血清及关节液上清IL-6、IP-10及IL-17的浓度.结果 (1)血清细胞因子浓度:sJIA组血清IL-6浓度明显高于健康对照组[28.0(4.2 ~59.2)ng/L vs.12.3(2.1 ~ 13.8) ng/L,P<0.05],但疑诊sJIA组与健康对照组相比无明显升高[11.8(7.7~39.2)ng/Lvs.12.3(2.1 ~13.8)ng/L,JP>0.05].sJIA组血清IL-17浓度高于健康对照组[14.0(9.8~ 34.3)ng/L vs.9.8(7.9 ~ 16.2)ng/L,P<0.05],pJIA组血清IL-17浓度与健康对照组相比无明显升高[14.2(9.9 ~ 16.9)ng/L vs.9.8(7.9 ~ 16.2)ng/L,P>0.05].(2) sJIA及pJIA组关节液中IP-10的浓度均分别高于两组血清[619.7(160.9,873.1)ng/L vs.64.8(27.4 ~ 111.9) ng/L,P<0.01;660.9(401.9,1349.8)ng/L vs.97.4(41.9 ~222.1)ng/L,P<0.01].关节液中IL-17浓度仅pJIA组显著高于血清[22.9(17.1,45.8) ng/L vs.14.2(9.9 ~ 16.9)ng/L,P<0.01].结论 (1)IL-6在sJIA发病中起重要作用,并且可能成为关节炎症早期的重要生物学标记.(2) sJIA发病机制中可能共同存在自身炎症反应和自身免疫反应.(3) IL-17在pJIA关节液局部高表达,而在外周血表达并不升高.(4)趋化因子IP-10在关节液和外周血中存在显著浓度梯度,可能是其发挥趋化作用,进而致sJIA关节损害的基础.%Objective To detect the disparity of three cytokines interleukin-6 (IL-6),interferoninducible protein 10 (IP-10) and interleukin-17 (IL-17) in peripheral blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).Method Serum concentrations of the three cytokines were measured in 27 patients with 13 systemic-onset JIA (sJIA),14

  10. 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.

  11. Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis

    DEFF Research Database (Denmark)

    Uysal, Hüseyin; Bockermann, Robert; Nandakumar, Kutty S

    2009-01-01

    Antibodies to citrulline-modified proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical...... collagen type II (CII) epitope (position 359-369; ARGLTGRPGDA) with or without arginines modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid demonstrates that cartilage-derived CII...

  12. Differentiation in vitro of inflammatory from non inflammatory synovial fluid by nuclear magnetic relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Teyssier, R.; Teyssier, M.; Colson, F.

    1987-01-01

    The differentiation between inflammatory and non inflammatory states has been performed using Nuclear Magnetic Resonance (NMR) in vitro by measuring relaxation times T/sub 1/ and T/sub 2/ in 84 synovials fluids obtained from various rheumatologic diseases. The results show that the T/sub 1//T/sub 2/ ratio is more sensitive to distinguish these two situations rather than the isolated T/sub 1/ or T/sub /2 values. In particular, high values of T/sub 1//T/sub 2/ ratio are found in septic arthritis.

  13. Septic arthritis of the acromioclavicular joint: an uncommon location.

    Science.gov (United States)

    Martínez-Morillo, Melania; Mateo Soria, Lourdes; Riveros Frutos, Anne; Tejera Segura, Beatriz; Holgado Pérez, Susana; Olivé Marqués, Alejandro

    2014-01-01

    Septic pyogenic arthritis of the acromioclavicular joint is a rare entity that occurs in immunosuppressed patients or those with discontinuity of defense barriers. There are only 15 cases described in the literature. The diagnosis is based on clinical features and the isolation of a microorganism in synovial fluid or blood cultures. The evidence of arthritis by imaging (MRI, ultrasound or scintigraphy) may be useful. Antibiotic treatment is the same as in septic arthritis in other locations. Staphylococcus aureus is the microorganism most frequently isolated. Our objective was to describe the clinical features, treatment and outcome of patients diagnosed with septic arthritis of the acromioclavicular joint at a Rheumatology Department. We developed a study with a retrospective design (1989-2012). The medical records of patients with septic arthritis were reviewed (101 patients). Those involving the acromioclavicular joint were selected (6 patients; 6%).

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

    Energy Technology Data Exchange (ETDEWEB)

    Oner, Ali Yusuf; Ucar, Murat; Akpek, Sergin; Tokgoz, Nil [Gazi University School of Medicine, Department of Radiology, Besevler-Ankara (Turkey)

    2007-06-15

    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.)

  15. Macrophages - silent enemies in juvenile idiopathic arthritis.

    Science.gov (United States)

    Świdrowska-Jaros, Joanna; Orczyk, Krzysztof; Smolewska, Elżbieta

    2016-07-06

    The inflammatory response by secretion of cytokines and other mediators is postulated as one of the most significant factors in the pathophysiology of juvenile idiopathic arthritis (JIA). The effect of macrophage action depends on the type of their activation. Classically activated macrophages (M1) are responsible for release of molecules crucial for joint inflammation. Alternatively activated macrophages (M2) may recognize self antigens by scavenger receptors and induce the immunological reaction leading to autoimmune diseases such as JIA. Molecules essential for JIA pathophysiology include: TNF-α, the production of which precedes synovial inflammation in rheumatoid arthritis; IL-1 as a key mediator of synovial damage; chemotactic factors for macrophages IL-8 and MCP-1; IL6, the level of which correlates with the radiological joint damage; MIF, promoting the secretion of TNF-α and IL-6; CCL20 and HIF, significant for the hypoxic synovial environment in JIA; GM-CSF, stimulating the production of macrophages; and IL-18, crucial for NK cell functions. Recognition of the role of macrophages creates the potential for a new therapeutic approach.

  16. Magnetic resonance imaging findings in horses with septic arthritis.

    Science.gov (United States)

    Easley, Jeremiah T; Brokken, Matthew T; Zubrod, Chad J; Morton, Alison J; Garrett, Katherine S; Holmes, Shannon P

    2011-01-01

    Fourteen horses with septic arthritis underwent high-field (1.5 T) magnetic resonance imaging (MRI). Septic arthritis was diagnosed based on results from historical and clinical findings, synovial fluid analyses and culture, and radiographic, ultrasonographic, arthroscopic, and histopathologic findings. MR findings included diffuse hyperintensity within bone and extracapsular tissue on fat-suppressed images in 14/14 horses (100%), joint effusion, synovial proliferation, and capsular thickening in 13/14 horses (93%), bone sclerosis in 11/14 horses (79%), and evidence of cartilage and subchondral bone damage in 8/14 horses (57%). Intravenous gadolinium was administered to five of the 14 horses and fibrin deposition was noted in all horses. Other findings after gadolinium administration included synovial enhancement in 4/5 (80%) horses, and bone enhancement in 1/5 (20%) horses. The MR findings of septic arthritis in horses were consistent with those reported in people. MRI may allow earlier and more accurate diagnosis of septic arthritis in horses as compared with other imaging modalities, especially when the clinical diagnosis is challenging. It also provides additional information not afforded by other methods that may influence and enhance treatment.

  17. 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.

  18. What Is Reactive Arthritis?

    Science.gov (United States)

    ... Arthritis PDF Version Size: 69 KB November 2014 What is Reactive Arthritis? Fast Facts: An Easy-to- ... Information About Reactive Arthritis and Other Related Conditions What Causes Reactive Arthritis? Sometimes, reactive arthritis is set ...

  19. Ultrastructural characteristics of the synovial membrane in osteoarthritic temporomandibular joints

    NARCIS (Netherlands)

    Dijkgraaf, LC; Liem, RSB; deBont, LGM

    1997-01-01

    Purpose: This study analyzed the ultrastructural characteristics of the synovial membrane in various stages of osteoarthritis (OA) of the temporomandibular joint (TMJ), and developed a classification of this involvement based on these morphologic characteristics. Patients and Methods: Synovial membr

  20. Reactive Arthritis

    Directory of Open Access Journals (Sweden)

    Eren Erken

    2013-06-01

    Full Text Available Reactive arthritis is an acute, sterile, non-suppurative and inflammatory arthropaty which has occured as a result of an infectious processes, mostly after gastrointestinal and genitourinary tract infections. Reiter syndrome is a frequent type of reactive arthritis. Both reactive arthritis and Reiter syndrome belong to the group of seronegative spondyloarthropathies, associated with HLA-B27 positivity and characterized by ongoing inflammation after an infectious episode. The classical triad of Reiter syndrome is defined as arthritis, conjuctivitis and urethritis and is seen only in one third of patients with Reiter syndrome. Recently, seronegative asymmetric arthritis and typical extraarticular involvement are thought to be adequate for the diagnosis. However, there is no established criteria for the diagnosis of reactive arthritis and the number of randomized and controlled studies about the therapy is not enough. [Archives Medical Review Journal 2013; 22(3.000: 283-299

  1. [Presence of riziform bodies in a patient with juvenile idiopathic arthritis: case report and literature review.

    Science.gov (United States)

    Campos, Leonardo Rodrigues; Sztajnbok, Fernanda Cardoso das Neves; Galvão, Stélio; Lessa, Marise de Araújo; Aymoré, Ierecê Lins; Sztajnbok, Flavio

    2014-10-23

    Riziform bodies are structures formed by fibrin and cells that can be found in the synovial fluid or attached to the synovium, and have this denomination due to its rice grain-like appearance. They have already been described in several diseases such as tuberculous arthritis, rheumatoid arthritis, and rarely in juvenile idiopathic arthritis (JIA). This is the case of a boy with a 4-month course of chronic monoarthritis of the left knee, with family history of sarcoidosis in which diagnostic investigation showed the presence of these riziform bodies in the synovial biopsy. Diagnostic investigation ruled out sarcoidosis, tuberculosis and malignancies, establishing the diagnosis of JIA. Our objective was to describe what we believe is the 9th case reported on the presence of riziform bodies in JIA, which are probably underdiagnosed, and should be considered mainly in cases of severe arthritis of difficult medical treatment.

  2. IL-23 Dependent and Independent Stages of Experimental Arthritis: No Clinical Effect of Therapeutic IL-23p19 Inhibition in Collagen-induced Arthritis

    NARCIS (Netherlands)

    F.H.J. Cornelissen (Ferry); P. Asmawidjaja (Patrick); A.M.C. Mus (Adriana); O.B.J. Corneth (Odilia); K. Kikly (Kristine); E.W. Lubberts (Erik)

    2013-01-01

    textabstractIL-23p19 deficient mice have revealed a critical role of IL-23 in the development of experimental autoimmune diseases, such as collagen-induced arthritis (CIA). Neutralizing IL-23 after onset of CIA in rats has been shown to reduce paw volume, but the effect on synovial inflammation and

  3. Clinical Pathological Analysis of Synovial Sarcoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate the clinical diagnosis and differential diagnosis of synovial sarcoma (SS).METHODS A total of 41 paraffin-embedded synovial sarcoma samples were examined by H&E staining, immunohistochemistry staining and the reverse transcriptase polymerase chain reaction (RT-PCR), in order to provide a scientific bases for diagnosis and differential diagnosis.RESULTS Twelve cases were a biphasic type, 22 cases were a monophasic fibrous type, and 7 cases were a poorly differentiated type. Thirty-six cases were both CK (and/or EMA) and Vim positive. Five cases were only Vim positive. A SYT-SSX fusion gene was detected in 18 cases by RT-PCR.CONCLUSION By observation of the histomorphology, immunohistochemistry markers and detection of a SYT-SSX fusion gene, we can make a clinical pathological diagnosis of synovial sarcoma.

  4. Synovial chondromatosis of the metacarpophalangeal joint of the ring finger

    OpenAIRE

    Ozcelik, Ismail Bulent; Kuvat, Samet Vasfi; Mersa, Berkan; Pilanci, Ozgur

    2010-01-01

    Synovial chondromatosis is an uncommon condition, characterized by multinodular cartilagineous proliferation of the joint synovium. There are only a few case reports of synovial chondromatosis involving the hand in the literature. A case of synovial chondromatosis of the ring finger is reported in this paper.

  5. Synovial chondromatosis of the metacarpophalangeal joint of the ring finger.

    Science.gov (United States)

    Ozçelik, Ismail Bülent; Kuvat, Samet Vasfi; Mersa, Berkan; Pilancı, Ozgür

    2010-01-01

    Synovial chondromatosis is an uncommon condition, characterized by multinodular cartilagineous proliferation of the joint synovium. There are only a few case reports of synovial chondromatosis involving the hand in the literature. A case of synovial chondromatosis of the ring finger is reported in this paper.

  6. Therapeutic effect of Rhizoma Dioscoreae Nipponicae on gouty arthritis based on the SDF-1/CXCR 4 and p38 MAPK pathway: an in vivo and in vitro study.

    Science.gov (United States)

    Lu, Fang; Liu, Lei; Yu, Dong-hua; Li, Xu-zhao; Zhou, Qi; Liu, Shu-min

    2014-02-01

    Rhizoma Dioscoreae Nipponicae (RDN) is a widely used traditional Chinese herb, which is used to treat arthroncus, arthrodynia and arthritis. As is known to us, inflammatory mechanisms have played an important role in the occurrence, course and prognosis of gouty arthritis (GA). The aim of this study was to determine the characteristic expressed proteins of synovium in GA rat and synovial cell. The rat model of GA was induced by monosodium urate (MSU) crystal. Tissue samples were assayed by immunohistochemical method. The effects of RDN on Stromal cell-derived factor 1 (SDF-1), CXCR 4 and p38 mitogen-activated protein kinase (MAPK) were investigated in MSU crystal-induced rat. The levels of SDF-1 and mitogen-activated kinase kinase (MKK) 3/6 were measured by Western Blot in interleukin-1β (IL-1β) incubated fibroblast-like synoviocytes (FLS). A significant increase in the levels of SDF-1, CXCR 4 and p38 MAPK were observed in MSU crystal-induced rat. The increased SDF-1 and MKK 3/6 levels were observed in IL-1β incubated FLS. With the treatment of RDN, the above changes were reverted back to near normal levels. RDN might have some therapeutic effects on GA through SDF-1/CXCR 4 and p38 MAPK pathway, and dioscin may be the active compound in RDN to exert therapeutic effect on GA.

  7. [Basic research overview in rheumatoid arthritis].

    Science.gov (United States)

    Iwasaki, Yukiko; Yamamoto, Kazuhiko

    2016-06-01

    Rheumatoid arthritis (RA) is a common autoimmune disease with a prevalence of 0.5-1.0% worldwide. Although advances in understanding the pathogenesis of RA have led to new therapeutics with good outcomes, the real cause of the disease is still unknown. RA is characterized by synovial inflammation and hyperplasia, which erodes cartilage and bone, and autoantibody production (rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA)). There are many critical questions on the mechanism of the disease onset and progression: How genetic and environmental factors interact with each other? Why does the inflammatory response localize in joints? What are the key players to perpetuate synovial inflammation? In this review, we summarize pathogenetic advances in these issues especially from the point of view of basic research.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Synovial Lipomatosis of the Glenohumeral Joint

    Directory of Open Access Journals (Sweden)

    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.

  10. Primary Renal Synovial Sarcoma: An Oncologic Surprise

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    H. Krishna Moorthy

    2014-09-01

    Full Text Available Primary renal synovial sarcoma is a rare tumor having a specific chromosomal translocation t(X; 18 (p11.2; q11.2. The clinical features of this tumor and radiologic appearances are quite similar to those of renal cell carcinoma. Confirmatory diagnosis requires fluorescent in situ hybridization or reverse transcriptase polymerase chain reaction validation for differentiating the tumors from sarcomatoid renal cell carcinoma. We present a case of primary renal synovial sarcoma that was diagnosed in a middle-aged man.

  11. Synovial Lipomatosis of the Glenohumeral Joint.

    Science.gov (United States)

    Beyth, Shaul; Safran, Ori

    2016-01-01

    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.

  12. Effect of Sodium Alginate Addition to Resveratrol on Acute Gouty Arthritis

    Directory of Open Access Journals (Sweden)

    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.

  13. Human synovial lubricin expresses sialyl Lewis x determinant and has L-selectin ligand activity.

    Science.gov (United States)

    Jin, Chunsheng; Ekwall, Anna-Karin Hultgård; Bylund, Johan; Björkman, Lena; Estrella, Ruby P; Whitelock, John M; Eisler, Thomas; Bokarewa, Maria; Karlsson, Niclas G

    2012-10-19

    Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Galβ1-3(GlcNAcβ1-6)GalNAcα1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation.

  14. Human Synovial Lubricin Expresses Sialyl Lewis x Determinant and Has L-selectin Ligand Activity*

    Science.gov (United States)

    Jin, Chunsheng; Ekwall, Anna-Karin Hultgård; Bylund, Johan; Björkman, Lena; Estrella, Ruby P.; Whitelock, John M.; Eisler, Thomas; Bokarewa, Maria; Karlsson, Niclas G.

    2012-01-01

    Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Galβ1–3(GlcNAcβ1–6)GalNAcα1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation. PMID:22930755

  15. Influence of rhTNFR:FC on expression of cartilage oligomeric matrix protein in synovial fluid and peripheral blood among juvenile idiopathic arthritis%注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对幼年特发性关节炎患儿外周血关节液软骨寡聚基质蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    狄亚珍; 吴菱; 王天波; 郑吉卡; 戴霞华

    2014-01-01

    Objective To explore the effect of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein injection (rhTNFR:FC) on the expression of cartilage oligomeric matrix protein (COMP) in the synovial fluid and peripheral blood of juvenile idiopathic arthritis (JIA); and to explore the clinical significance of COMP for JIA and the relationship between rhTNFR:FC and COMP in JIA.Methods Thirty-five patients with JIA (JIA group),30 patients with traumatic arthritis (trauma group) and 30 patients with indirect inguinal hernia hernioplasty (normal group) were included.Peripheral blood from all enrolled patients and synovial fluid from 15 JIA and 10 trauma arthritis were obtained for COMP detection before the treatment.Fifteen JIA (group A) patients were treated with combined rhTNFR:FC,diseasemodifying antirheumatic drugs (DMARDs) and non-steroid anti-inflammatory drugs (NSAIDs),20 JIA (group B) were treated with combined DMARDs and NSAIDs.After three to six months' treatment and when the disease were in remission,peripheral blood from group A and B were drawn for COMP detection.In group A,the synovial fluid from 5 patients were obtained for COMP detection after treatment.At the same time,such as tender joint count (TJC),swollen joint count (SJC),time for morning stiffness,blood routine,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) and other parameters before and after treatment were measured.The level of COMP was tested by double antibody sandwich enzyme-linked immunosorbent assay.The measurement data were tested for variance and independent sample t-test; and the enumeration data were tested by chi-squared or Fisher's exact test.Pearson's correlation analysis was adopted to analyze the association among the variables.Results ① The blood COMP level before treatment was (0.77±0.29) ng/ml in the JIA group,(1.00±0.28) ng/ml in the traumatic arthritis group,and (1.33±0.37) ng/ml in the normal control group.The level in the former two

  16. RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro

    NARCIS (Netherlands)

    Steenvoorden, M.M.C.; Toes, R.E.M.; Ronday, H.K.; Huizinga, T.W.J.; Groot, J. de

    2007-01-01

    Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristi

  17. Abundant lubricin expression suggests a link between synoviocytes, synovial tumors, and myxomas.

    Science.gov (United States)

    Solka, Kathryn A; Schmid, Thomas M; Miller, Ira J

    2016-10-01

    Progenitor cell differentiation into fibroblast-like synoviocytes (FLSs) and their ensuing phenotypic changes are incompletely explored. Synovial lining is composed of intimal macrophages and FLSs. FLSs have epithelioid morphology and directionally secrete components of synovial fluid, including lubricin. We stained human tissues and tumors using two anti-lubricin antibodies. Lubricin was found in FLSs in synovium and in tenosynovial giant cell tumors (TSGCTs) and not in the associated monocyte/macrophage cells, which were identified by double immunostaining for CD163. In TSGCTs, giant cells, known to form by fusion of mononuclear cells, were negative for both lubricin and CD163. Occasional mononuclear cells with the same phenotype were also seen, suggesting that the precursors of the giant cells are derived from the minor CD163-negative monocyte subset. Lubricin was also detected in intramuscular myxomas, in early myxoid changes of ganglion cysts, and in one of five low-grade myxofibrosarcomas, but not in other fibroconnective tissues, epithelial tissues, or other tumors tested. This suggests that lubricin expression may typify adaptive and neoplastic changes along a pathway toward FLSs. Further support for this concept comes from ganglion cysts and juxta-articular myxoma tumors, which show a spectrum of myxoid, cystic and synovial differentiation, and in which moderate lubricin staining of myxoid stroma was seen.

  18. Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis

    Directory of Open Access Journals (Sweden)

    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.

  19. [Septic arthritis in two young children caused by unusual gram-negative pathogens].

    Science.gov (United States)

    Bruijn, J; Verhage, J; Bosboom, R W; Brus, F

    2000-07-29

    Two children, a girl aged 2 years and a boy aged 10 months, were moderately ill with signs of inflammation of the left and the right knee, respectively. Both had had pharyngitis, and the boy also had paronychia of the right foot. The Gram preparation of synovial fluid showed Gram-positive cocci in the girl, while Kingella kingae was cultured. In the boy, a Moraxella was cultured from the synovial fluid using an aerobic blood culture system. Both recovered without sequelae after adequate antibiotic treatment. The micro-organisms cultured were Gram-negative bacteria, which are rarely seen in septic arthritis and are difficult to demonstrate. In young children, septic arthritis often presents with mild symptoms and inconclusive laboratory findings. Even if the Gram preparation of the synovial fluid shows no micro-organisms, unusual pathogens may be isolated by means of an aerobic blood culture system.

  20. SNAP-23 and VAMP-3 contribute to the release of IL-6 and TNFα from a human synovial sarcoma cell line.

    Science.gov (United States)

    Boddul, Sanjay V; Meng, Jianghui; Dolly, James Oliver; Wang, Jiafu

    2014-02-01

    Fibroblast-like synoviocytes are important mediators of inflammatory joint damage in arthritis through the release of cytokines, but it is unknown whether their exocytosis from these particular cells is SNARE-dependent. Here, the complement of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) in human synovial sarcoma cells (SW982) was examined with respect to the secretion of interleukin-6 (IL-6) and tumour necrosis factor α (TNFα), before and after knockdown of a synaptosome-associated protein of molecular mass 23 kDa (SNAP-23) or the vesicle-associated membrane protein 3 (VAMP-3). Wild-type SW982 cells expressed SNAP-23, VAMP-3, syntaxin isoforms 2-4 and synaptic vesicle protein 2C (SV2C). These cells showed Ca²⁺-dependent secretion of IL-6 and TNFα when stimulated by interleukin-1β (IL-1β) or in combination with K⁺ depolarization. Specific knockdown of SNAP-23 or VAMP-3 decreased the exocytosis of IL-6 and TNFα; the reduced expression of SNAP-23 caused accumulation of SV2 in the peri-nuclear area. A monoclonal antibody specific for VAMP-3 precipitated SNAP-23 and syntaxin-2 (and syntaxin-3 to a lesser extent). The formation of SDS-resistant complexes by SNAP-23 and VAMP-3 was reduced upon knockdown of SNAP-23. Although the syntaxin isoforms 2, 3 and 4 are expressed in SW982 cells, knockdown of each did not affect the release of cytokines. Collectively, these results show that SNAP-23 and VAMP-3 participate in IL-1β-induced Ca²⁺-dependent release of IL-6 and TNFα from SW982 cells.

  1. Prediction of response to therapy in rheumatoid arthritis : Lost in validation

    NARCIS (Netherlands)

    Cuppen, B.V.J.

    2017-01-01

    Introduction Rheumatoid arthritis (RA) is a chronic, disabling disease that mainly affects the synovial joints. With a large arsenal of treatments among which tumor necrosis factor-alpha inhibitors (TNFi’s), RA disease activity decreases sufficiently in most but not all cases. The identification of

  2. Associations of Killer Cell Immunoglobulin-Like Receptor Genes with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    S. Ramírez-De los Santos

    2012-01-01

    Full Text Available Objective: Rheumatoid Arthritis (RA is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28null T-cells, both present in synovial membrane of RA. Therefore we evaluated the associations of KIR genes with RA.

  3. 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

  4. Expression of lectin-like transcript 1, the ligand for CD161, in rheumatoid arthritis

    NARCIS (Netherlands)

    Chalan, P.; Bijzet, J.; Kroesen, B.-J.; Brouwer, Liesbeth; Boots, M.

    2015-01-01

    Background: Precursor Th17 lineage cells expressing CD161 are implicated in rheumatoid arthritis pathogenesis. CD4+CD161+ T cells were found to accumulate in RA synovial fluid and tissue where they may acquire a non-classical T-helper 1 phenotype. The sole endogenous ligand for CD161 is lectin-like

  5. Prospective comparative study of patients with culture proven and high suspicion of adult onset septic arthritis

    OpenAIRE

    GUPTA, M.; Sturrock, R; Field, M

    2003-01-01

    Objective: To investigate whether patients with acute septic arthritis (SA) diagnosed by positive synovial fluid (SF) culture (Newman grade A) have different clinical and serological features from those with sterile SF in whom there is nonetheless a high suspicion of SA (Newman grades B and C).

  6. Septic Arthritis Caused by Legionella dumoffii in a Patient with Systemic Lupus Erythematosus-Like Disease

    NARCIS (Netherlands)

    Flendrie, M.; Jeurissen, S.M.F.; Franssen, M.; Kwa, D.; Klaassen, C.; Vos, F.

    2011-01-01

    We describe a patient with systemic lupus erythematosus (SLE)-like disease on immunosuppressive treatment who developed septic arthritis of the knee involving Legionella dumoffii. Cultures initially remained negative. A broad-range 16S PCR using synovial fluid revealed L. dumoffii rRNA genes, a find

  7. 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...

  8. 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...... additional information in selected cases but did not in the present study increase the sensitivity of the method...

  9. Therapeutic Drug-Monitoring of Methotrexate-Polyglutamates in Rheumatoid Arthritis

    NARCIS (Netherlands)

    E. den Boer (Ethan)

    2014-01-01

    markdownabstract__Abstract__ Rheumatoid Arthritis (RA) is a chronic autoimmune disease, characterized by the swelling of joints, uncontrolled proliferation of synovial tissue and multisystem co-morbidities. RA mainly affects the joints of the hands, feet, knees, wrist and elbows, with joint damage

  10. CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial

    NARCIS (Netherlands)

    A.W.R. van Kuijk; C.E. Vergunst; D.M. Gerlag; B. Bresnihan; J.J. Gomez-Reino; R. Regine; P.C. Verschueren; C. van der Leij; M. Maas; M.C. Kraan; P.P. Tak

    2010-01-01

    Objective C-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects o

  11. GLUT1 Expression in Synovial Sarcomas

    Directory of Open Access Journals (Sweden)

    Gülşah KAYGUSUZ

    2009-09-01

    Full Text Available Objective: In this study, the role of GLUT1 expression in synovial sarcomas and its association with disease pathogenesis were examined.Materials and Methods: Twenty two cases of synovial sarcoma were included in this study. The clinicopathological features of the cases, such as age, sex, localization of tumor, information of primary or metastatic tumor, histopathological type were recorded. The tissue microarray paraffin block containing tumor tissues was built by using tissue microarrayer. GLUT1 expression was analyzed on tissue sections by immunohistochemistry.Results: A total of 22 cases (mean age 36 years; range 14-54 years were analyzed. All cases except one were primary tumors. The tumors showed monophasic histological type in 13 cases and biphasic type in 9 cases. GLUT1 expression was found in 3 cases with biphasic type (14%. The cytoplasmic and incomplete membranous GLUT1 expression was seen in the tumor cells showing epithelial-glandular differentiation, whereas spindled cells were negative.Conclusion: Although GLUT1 expression is a diagnostic marker for juvenile capillary hemangioma and perineural tumors, both of which included in the group of mesenchymal tumors, it can be seen in a subset of synovial sarcomas. In our series, the observation of GLUT1 expression especially in the epithelial component of biphasic synovial sarcomas suggests that; i GLUT1 may be relatively used by tumoral cells composing epithelial component of the tumor, and ii the spindle cell component of the tumor would have been positive for other glucose transporters. The finding of uncommon GLUT1 expression in synovial sarcomas is indirectly consistent with the reported results of decreased standardized uptake value by Positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose method in the literature.

  12. Kingella kingae septic arthritis with endocarditis in an adult.

    Science.gov (United States)

    Elyès, Bouajina; Mehdi, Ghannouchi; Kamel, Ben Haj Slama; Hela, Zeglaoui; Imen, Ben Smida

    2006-07-01

    Kingella kingae is part of the nonpathogenic flora normally found in the oral cavity and pharynx. Recent reports have established that K. kingae can cause invasive infections in pediatric patients. Few cases have been described in adults, however. We report a case of K. kingae arthritis of the knee followed by endocarditis in a 59-year-old woman. Physicians and microbiologists should be alert to the possibility of K. kingae infection. K. kingae is easy to detect provided its specific culture requirements are taken into account. Synovial fluid inoculation into blood culture vials considerably increases the likelihood of K. kingae recovery in patients with septic arthritis.

  13. Pathogenesis of rheumatoid arthritis and the immune response

    Energy Technology Data Exchange (ETDEWEB)

    Scheinberg, M.A.

    1983-08-01

    The interrelationship among lymphocytes, macrophages, and neutrophils appears to be an important aspect of the synovial inflammation that is characteristic of rheumatoid arthritis. In a study comparing gold sodium aurothiomalate (GST) with auranofin (Au), an orally absorbed compound, both appeared to inhibit the disease process and no difference between parenteral and oral administration was observed. Another study involved two groups of nine patients with severe rheumatoid arthritis. One group underwent plasmapheresis. The second group underwent total lymphoid irradiation. Both agents appeared to inhibit the disease process. Plasmapheresis was better tolerated that irradiation.

  14. Polyarticular septic arthritis in an 11-year-old child.

    Science.gov (United States)

    Campanilho-Marques, Raquel; Novelli, Vas; Brogan, Paul A; Eleftheriou, Despina

    2014-08-01

    A child with polyarthritis is always a diagnostic challenge for the treating physician. Polyarthritis can be a clinical manifestation of diverse disease processes, and the differential diagnosis is understandably very broad. We present a case of polyarticular septic arthritis, which is osteomyelitis complicated, caused by Streptococcus pyogenes identified by 16S polymerase chain reaction (PCR) in a healthy child, with previous synovial fluid cultures negative. This case underlines the importance of early aggressive therapy and the role of PCR/16S ribosomal bacterial DNA amplification to detect the causative microorganisms in septic arthritis when cultures remain negative.

  15. 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.)

  16. Clonal dominance among T-lymphocyte infiltrates in arthritis

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-02-01

    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) ..beta..-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.

  17. Comparison of clinical and biologic features of Kingella kingae and Staphylococcus aureus arthritis at initial evaluation.

    Science.gov (United States)

    Basmaci, Romain; Lorrot, Mathie; Bidet, Philippe; Doit, Catherine; Vitoux, Christine; Penneçot, Georges; Mazda, Keyvan; Bingen, Edouard; Ilharreborde, Brice; Bonacorsi, Stéphane

    2011-10-01

    We conducted a retrospective study comparing the presenting clinical and biologic features of 64 children who had septic arthritis caused by Kingella kingae with 26 children who had septic arthritis caused by Staphylococcus aureus. Children with K. kingae septic arthritis were significantly younger than those with S. aureus septic arthritis. Otherwise, there were no significant differences between the 2 groups with respect to fever, location, white blood cell count, synovial fluid cell count, C-reactive protein, or serum fibrinogen. However, the clinical course was significantly better for children with septic arthritis caused by K. kingae as evidenced by shorter hospitalization and fewer adverse events. Presumptive antibiotic therapy for septic arthritis in young infants should take into account both of these pathogens, even in case of mild presentation.

  18. Salmonella enteridis Septic Arthritis: A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    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.

  19. Psoriatic arthritis: imaging techniques

    Directory of Open Access Journals (Sweden)

    E. Lubrano

    2012-06-01

    Full Text Available Imaging techniques to assess psoriatic arthritis (PsA include radiography, ultrasonography (US, magnetic resonance imaging (MRI, computed tomography (CT and bone scintigraphy. The radiographic hallmark of PsA is the combination of destructive changes (joint erosions, tuft resorption, osteolysis with bone proliferation (including periarticular and shaft periostitis, ankylosis, spur formation and non-marginal syndesmophytes. US has an increasing important role in the evaluation of PsA. In fact, power Doppler US is useful mainly for its ability to assess musculoskeletal (joints, tendons, entheses and cutaneous (skin and nails involvement, to monitor efficacy of therapy and to guide steroid injections at the level of inflamed joints, tendon sheaths and entheses. MRI allows direct visualization of inflammation in peripheral and axial joints, and peripheral and axial entheses, and has dramatically improved the possibilities for early diagnosis and objective monitoring of the disease process in PsA. MRI has allowed explaining the relationships among enthesitis, synovitis and osteitis in PsA, supporting a SpA pattern of inflammation where enthesitis is the primary target of inflammation. CT has little role in assessment of peripheral joints, but it may be useful in assessing elements of spine disease. CT accuracy is similar to MRI in assessment of erosions in sacroiliac joint involvement, but CT is not as effective in detecting synovial inflammation. Bone scintigraphy lacks specificity and is now supplanted with US and MRI techniques.

  20. Expression of Prostaglandin E2 Enzymes in the Synovium of Arthralgia Patients at Risk of Developing Rheumatoid Arthritis and in Early Arthritis Patients.

    Directory of Open Access Journals (Sweden)

    Maria J H de Hair

    Full Text Available Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA. A major pathway involved in pain is the prostaglandin (PG E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients.Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies with arthralgia (n=15 and/or a positive family history of RA (n=8, who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug naïve who after 2 years follow up fulfilled classification criteria for RA (n=63, spondyloarthritis (SpA; n=14, or had unclassified arthritis (UA; n=27. In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH.In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals. However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients.Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.

  1. Effects of IL-22 on rheumatoid arthritis fibroblast-like synoviocytes%IL-22对类风湿关节炎成纤维样滑膜细胞的作用

    Institute of Scientific and Technical Information of China (English)

    刘梦; 刘岩; 杨梦如; 莫碧瑶; 潘云峰

    2016-01-01

    目的:探究白细胞介素(IL)-22对类风湿关节炎(RA)成纤维样滑膜细胞(FLSs)功能的影响及机制。方法:组织块法培养RA-FLSs。将不同浓度(0、1、10、100μg/L)的重组人源性IL-22(rhIL-22)与RA-FLSs共培养24 h、48 h、72 h,CCK-8法检测细胞活力的改变;利用10μg/L的rhIL-22作用于RA-FLSs 24 h,流式细胞术检测细胞周期改变。 rhIL-22和/或信号转导和转录因子3( STAT3)特异性抑制剂STA-21以不同浓度作用RA-FLSs 24 h,Western blot法检测Bcl-2和p-STAT3蛋白水平的变化。结果:不同浓度的rhIL-22作用于RA-FLSs 24 h、48 h、72 h后,RA-FLSs细胞活力明显增高,均显著高于对照组(P<0.05)。 rhIL-22刺激RA-FLSs后,S期和G2/M期细胞明显增多,G0/G1期细胞减少。 Western blot法检测结果提示rhIL-22可上调RA-FLSs中Bcl-2、p-STAT3的蛋白水平,而STA-21单用或联用rhIL-22均可抑制RA-FLSs中Bcl-2及p-STAT3的表达( P<0.05)。结论:IL-22在RA-FLSs细胞活力和周期调节中起重要作用,且STAT3在IL-22促RA-FLSs细胞Bcl-2表达的过程中起关键作用,提示IL-22可能对RA-FLSs凋亡有一定的影响。%AIM:To determine the effects and mechanisms of interleukin-22 (IL-22) on the fibroblast-like sy-noviocytes ( FLSs) from rheumatoid arthritis ( RA) patients.METHODS:RA-FLSs were cultured by tissue culture meth-od.RA-FLSs were incubated with different concentrations of IL-22 (0,1,10,100μg/L) for 24 h, 48 h and 72 h.The cell viability was examined by CCK-8 assay.IL-22 at concentration of 10 μg/L was used to stimulate RA-FLSs for 24 h, and the change of cell cycle distribution was identified by flow cytometry.The effects of IL-22 at concentrations of 0, 1, 10, 100μg/L and/or STA-21 (a STAT3 inhibitor at concentrations of 0, 25, 50μmol/L) on the protein levels of Bcl-2 and p-STAT3 in the RA-FLSs were

  2. Juvenile Arthritis

    Science.gov (United States)

    ... increased risk of developing an inflammatory eye problem (iritis or uveitis). Eye inflammation may persist independently of the arthritis. Because iritis usually does not cause symptoms, regular exams by ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  4. Rheumatoid Arthritis Educational Video Series

    Science.gov (United States)

    ... Corner / Patient Webcasts / Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos ... Your Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life ...

  5. Posttraumatic Arthritis

    OpenAIRE

    Pickering, Robert D.

    1984-01-01

    Posttraumatic arthritis (i.e., degenerative joint disease secondary to injury) is a particular problem in young, active patients. It limits the activities of these vigorous individuals, and the compromised joint must be endured for a long time. The knee is used as an example of a joint commonly involved in this process. Conditions predisposing patients to posttraumatic arthritis are discussed, as are some treatment modalities, including rest, ice therapy, anti-inflammatory medications, physio...

  6. Cytokines in juvenile rheumatoid arthritis (JRA).

    Science.gov (United States)

    Mangge, H; Schauenstein, K

    1998-06-01

    Juvenile rheumatoid arthritis (JRA), unlike rheumatoid arthritis of adulthood (RA), is a heterogenous disease comprising at least five subtypes that differ in clinical course and prognosis, and require different therapeutical approaches. As compared to RA, the production of local and systemic cytokines in JRA have not yet been as extensively investigated. In this article we review the available literature on cytokine expression in serum and synovial fluid in all five different subtypes of JRA. Even though the data are still fragmentary, the evidence so far suggests that the determination of serum cytokines yields relevant information as to clinical subtype and inflammatory activity of the disease. Furthermore, the cytokine data suggest that the pathogenesis of JRA may even by more heterogenous than defined by the clinical subtypes. Finally, future directions of research in this area are proposed, and-based on the latest results-arguments for (anti)cytokine therapies in JRA are critically discussed.

  7. Induction of lyme arthritis in LSH hamsters

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-09-01

    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.

  8. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ...

  9. Development of the synovial membrane in the rat temporomandibular joint as demonstrated by immunocytochemistry for heat shock protein 25.

    Science.gov (United States)

    Ikeda, Nobuyuki; Nozawa-Inoue, Kayoko; Takagi, Ritsuo; Maeda, Takeyasu

    2004-07-01

    The synovial lining layer of the temporomandibular joint (TMJ) consists of macrophage-like type A cells and fibroblast-like type B cells. Until now, little information has been available on the development of the synovial membrane in TMJ. In the present study we examined the development of the synovial lining layer in the rat TMJ by light- and electron-microscopic immunocytochemistry for heat shock protein (Hsp) 25, which is a useful marker for type B cells. At embryonic day 19 (E19), a few Hsp25-positive cells first appeared in the upper portion of the developing condyle. During the formation of the upper articular cavity (E21 to postnatal day 1 (P1)), a few positive cells were arranged on its surface. Immunoelectron microscopy demonstrated that these cells had ultrastructural features of fibroblast-like type B cells. In addition, some Hsp25-positive cells moved to the deep portion by extending their cytoplasmic processes toward the articular cavity at P3. At that time, the presence of typical macrophage-like type A cells in the lining layer was confirmed by immunoelectron microscopy. The slender processes of Hsp25-positive cells showed a continuous covering with the synovial surface at P7, followed by a drastic increase in the Hsp25-positive cells at P15 and later, when active jaw movement occurred. These findings suggested that the arrangement and morphological maturation of type B cells are closely related to the formation of the articular cavity in the embryonic period and the commencement of active jaw movement after birth, respectively.

  10. Synovial membrane involvement in osteoarthritic temporomandibular joints - A light microscopic study

    NARCIS (Netherlands)

    Dijkgraaf, LC; Liem, RSB; deBont, LGM

    1997-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kirkhus, Eva [Oslo University Hospital, Rikshospitalet, Department of Radiology, Oslo (Norway); Flatoe, Berit; Smith, Hans-Joergen [Oslo University Hospital, Rikshospitalet and University of Oslo, Faculty of Medicine, Department of Radiology, Oslo (Norway); Riise, Oeystein [Oslo University Hospital, Rikshospitalet, Department of Pediatrics, Oslo (Norway); Reiseter, Tor [Oslo University Hospital, Ullevaal, Department of Radiology, Oslo (Norway)

    2011-04-15

    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.)

  12. 5. Diagnosis and Treatment of Lyme Arthritis

    Science.gov (United States)

    Arvikar, Sheila L.; Steere, Allen C.

    2015-01-01

    SYNOPSIS In the United States, Lyme arthritis is the most common feature of late stage infection with the tick-borne spirochete, Borrelia burgdorferi, usually beginning months after the initial tick bite. However, in some patients, including most of those seen today, the earlier phases of the infection are asymptomatic and arthritis is the presenting manifestation of the disease. Patients with Lyme arthritis have intermittent or persistent attacks of joint swelling and pain in one or a few large joints, especially the knee, usually over a period of several years, without prominent systemic manifestations. Serologic testing is the mainstay of diagnosis. Synovial fluid PCR testing for B. burgdorferi DNA is often positive prior to treatment, but it is not a reliable marker of spirochetal eradication after antibiotic therapy. Responses to oral or intravenous antibiotic treatment are generally excellent, although a small percentage of patients have persistent synovitis after 2-3 months of oral and IV antibiotics, which usually then responds to anti-inflammatory therapies, disease modifying anti-rheumatic drugs (DMARDs), or synovectomy. This chapter reviews the clinical manifestations, diagnosis, and management of Lyme arthritis. PMID:25999223

  13. Fibroblast-like synoviocyte-chondrocyte interaction in cartilage degradation

    NARCIS (Netherlands)

    Steenvoorden, M.M.C.; Bank, R.A.; Ronday, H.K.; Toes, R.E.M.; Huizinga, T.W.J.; Groot, J. de

    2007-01-01

    Objective: In vitro models for joint diseases often focus on a single cell type, such as chondrocytes in osteoarthritis (OA) or fibroblast-like synoviocytes (synoviocytes) in rheumatoid arthritis (RA). However, these joint diseases affect the whole joint and interaction between chondrocytes and syno

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

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    2012-01-01

    Full Text Available 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.

  16. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies.

    LENUS (Irish Health Repository)

    Moran, Ellen M

    2009-01-01

    INTRODUCTION: The aim of this study was to examine IL-17A in patients, following anti-TNF-alpha therapy and the effect of IL-17A on matrix turnover and cartilage degradation. METHODS: IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +\\/- TNF-alpha and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP\\/TIMP were assessed in patients pre\\/post biologic therapy. RESULTS: IL-17A levels were higher in RA vs osteoarthritis (OA)\\/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-alpha and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-alpha or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1\\/TIMP4, MMP3\\/TIMP1 and MMP3\\/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients. CONCLUSIONS: IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.

  17. Kingella kingae expresses type IV pili that mediate adherence to respiratory epithelial and synovial cells.

    Science.gov (United States)

    Kehl-Fie, Thomas E; Miller, Sara E; St Geme, Joseph W

    2008-11-01

    Kingella kingae is a gram-negative bacterium that colonizes the respiratory tract and is a common cause of septic arthritis and osteomyelitis. Despite the increasing frequency of K. kingae disease, little is known about the mechanism by which this organism adheres to respiratory epithelium and seeds joints and bones. Previous work showed that K. kingae expresses long surface fibers that vary in surface density. In the current study, we found that these fibers are type IV pili and are necessary for efficient adherence to respiratory epithelial and synovial cells and that the number of pili expressed by the bacterium correlates with the level of adherence to synovial cells but not with the level of adherence to respiratory cells. In addition, we established that the major pilin subunit is encoded by a pilA homolog in a conserved region of the chromosome that also contains a second pilin gene and a type IV pilus accessory gene, both of which are dispensable for pilus assembly and pilus-mediated adherence. Upon examination of the K. kingae genome, we identified two genes in physically separate locations on the chromosome that encode homologs of the Neisseria PilC proteins and that have only a low level homology to each other. Examination of mutant strains revealed that both of the K. kingae PilC homologs are essential for a wild-type level of adherence to both respiratory epithelial and synovial cells. Taken together, these results demonstrate that type IV pili and the two PilC homologs play important roles in mediating K. kingae adherence.

  18. Kingella kingae Expresses Type IV Pili That Mediate Adherence to Respiratory Epithelial and Synovial Cells▿

    Science.gov (United States)

    Kehl-Fie, Thomas E.; Miller, Sara E.; St. Geme, Joseph W.

    2008-01-01

    Kingella kingae is a gram-negative bacterium that colonizes the respiratory tract and is a common cause of septic arthritis and osteomyelitis. Despite the increasing frequency of K. kingae disease, little is known about the mechanism by which this organism adheres to respiratory epithelium and seeds joints and bones. Previous work showed that K. kingae expresses long surface fibers that vary in surface density. In the current study, we found that these fibers are type IV pili and are necessary for efficient adherence to respiratory epithelial and synovial cells and that the number of pili expressed by the bacterium correlates with the level of adherence to synovial cells but not with the level of adherence to respiratory cells. In addition, we established that the major pilin subunit is encoded by a pilA homolog in a conserved region of the chromosome that also contains a second pilin gene and a type IV pilus accessory gene, both of which are dispensable for pilus assembly and pilus-mediated adherence. Upon examination of the K. kingae genome, we identified two genes in physically separate locations on the chromosome that encode homologs of the Neisseria PilC proteins and that have only a low level homology to each other. Examination of mutant strains revealed that both of the K. kingae PilC homologs are essential for a wild-type level of adherence to both respiratory epithelial and synovial cells. Taken together, these results demonstrate that type IV pili and the two PilC homologs play important roles in mediating K. kingae adherence. PMID:18757541

  19. Gouty arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Barthelemy, C.R.; Nakayama, D.A.; Lightfoot, R.W. Jr.; Wortmann, R.L.; Carrera, G.F.

    1984-01-01

    A prospective analysis of 60 patients with gout was undertaken to evaluate the radiographic spectrum of gouty arthritis in patients treated in the era of hypouricemic therapy. Twenty-two of these patients were clinically tophaceous; 36 were considered to have radiographic findings diagnostic of gouty arthritis by strict radiographic criteria. Up to 24% of the patients denied symptoms in joints with radiographic changes of gout; 42% with no evidence of tophi on clinical examination had radiographic changes characteristic of gout. Radiographic assessment can be extremely helpful in the management of gout by documenting the degree and extent of bony involvement, particularly in patients with limited symptoms or without clinical tophi.

  20. Arthritis in the highlands of Papua New Guinea.

    Science.gov (United States)

    Pile, K D; Richens, J E; Laurent, R M; Bhatia, K; Prasad, M L; Lupiwa, T; Hudson, B J; Tapsall, J; McPetrie, R

    1993-01-01

    Acute polyarthritis is an important cause of morbidity in many tropical countries. Classification has often been difficult, with the term tropical polyarthritis used for those in whom a diagnosis could not be made. The implication that this is a distinct entity is probably incorrect, with likely causes being septic arthritis or post-infective reactive arthritis. This study aimed to determine the types of arthritis found in 43 patients (30 men) presenting consecutively to the Goroka Base Hospital in the Eastern Highlands of Papua New Guinea. Gonococcal arthritis was diagnosed in eight patients (six men) on the basis of isolation of Neisseria gonorrhoeae from the joint aspirate. In all cases the N gonorrhoeae was identified by the closed culture system on chocolate agar, but not always by routine plating. There were no specific clinical features that identified patients with a gonococcal septic arthritis. The remaining 34 patients had an undifferentiated oligoarthritis. The pattern of arthritis in men and women was of a lower limb pauciarticular arthritis with a predilection for the knee and ankle joints. A total of 30% of male patients had a history of urethral discharge and 44% of all patients had preceding diarrhoea. Arthritis was the only feature in 59% of patients and in 32% there was an associated enthesitis. In this study most patients had an oligoarthritis consistent with a reactive arthritis or a septic arthritis due to N gonorrhoeae. Broth inoculation of synovial fluid was the best method to isolate N gonorrhoeae, with standard methods for gonococcal isolation failing in some patients. It is recommended that the term 'tropical polyarthritis' is no longer used as it does not refer to a specific entity but consists of several known arthritides.

  1. Tetrandrine inhibits migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes through down-regulating the expressions of Rac1, Cdc42, and RhoA GTPases and activation of the PI3K/Akt and JNK signaling pathways.

    Science.gov (United States)

    Lv, Qi; Zhu, Xian-Yang; Xia, Yu-Feng; Dai, Yue; Wei, Zhi-Feng

    2015-11-01

    Tetrandrine (Tet), the main active constituent of Stephania tetrandra root, has been demonstrated to alleviate adjuvant-induced arthritis in rats. The present study was designed to investigate the effects of Tet on the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and explore the underlying mechanisms. By using cultures of primary FLS isolated from synoviums of RA patients and cell line MH7A, Tet (0.3, 1 μmol·L(-1)) was proven to significantly impede migration and invasion of RA-FLS, but not cell proliferation. Tet also greatly reduced the activation and expressions of matrix degrading enzymes MMP-2/9, the expression of F-actin and the activation of FAK, which controlled the morphologic changes in migration process of FLS. To identify the key signaling pathways by which Tet exerts anti-migration effect, the specific inhibitors of multiple signaling pathways LY294002, Triciribine, SP600125, U0126, SB203580, and PDTC (against PI3K, Akt, JNK, ERK, p38 MAPK and NF-κB-p65, respectively) were used. Among them, LY294002, Triciribine, and SP600125 were shown to obviously inhibit the migration of MH7A cells. Consistently, Tet was able to down-regulate the activation of Akt and JNK as demonstrated by Western blotting assay. Moreover, Tet could reduce the expressions of migration-related proteins Rho GTPases Rac1, Cdc42, and RhoA in MH7A cells. In conclusion, Tet can impede the migration and invasion of RA-FLS, which provides a plausible explanation for its protective effect on RA. The underlying mechanisms involve the reduction of the expressions of Rac1, Cdc42, and RhoA, inhibition of the activation of Akt and JNK, and subsequent down-regulation of activation and/or expressions of MMP-2/9, F-actin, and FAK.

  2. Synovial fluid matrix metalloproteinase-2 and -9 activities in dogs suffering from joint disorders.

    Science.gov (United States)

    Murakami, Kohei; Maeda, Shingo; Yonezawa, Tomohiro; Matsuki, Naoaki

    2016-07-01

    The activity of matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fluids (SF) sampled from dogs with joint disorders was investigated by gelatin zymography and densitometry. Pro-MMP-2 showed similar activity levels in dogs with idiopathic polyarthritis (IPA; n=17) or canine rheumatoid arthritis (cRA; n=4), and healthy controls (n=10). However, dogs with cranial cruciate ligament rupture (CCLR; n=5) presented significantly higher pro-MMP-2 activity than IPA and healthy dogs. Meanwhile, dogs with IPA exhibited significantly higher activity of pro- and active MMP-9 than other groups. Activity levels in pro- and active MMP-9 in cRA and CCLR dogs were not significantly different from those in healthy controls. Different patterns of MMP-2 and MMP-9 activity may reflect the differences in the underlying pathological processes.

  3. [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.

  4. Pharmacokinetics and penetration into synovial fluid of systemical and electroporation administered sinomenine to rabbits.

    Science.gov (United States)

    Yan, Huan; Yan, Miao; Li, Huan-De; Jiang, Pei; Deng, Yang; Cai, Hua-Lin

    2015-06-01

    Sinomenine is an anti-rheumatoid arthritis (RA) drug derived from the Sinomenium acutum. The major site of RA treatment is within the synovial compartment. However, the pharmacokinetic and penetration into synovial fluid (SF) of sinomenine have not been reported. In our study, the pharmacokinetics and penetration into SF of systemic and electroporation administered sinomenine were investigated by microdialysis incorporated with HPLC-MS/MS. Sinomenine went into plasma and SF more rapidly with higher peak concentration (Cmax ) by intramuscular injection compared with oral administration. The area under the concentration-time graph (AUC0-∞ ) of intramuscularly injected sinomenine was 1,403,294.75 ± 125,534.567 ng min/mL in plasma and 456,116.37 ± 62,648.36 ng min/mL in SF, which were equivalent with those for an oral dose. These results indicated that equal amounts of sinomenine could penetrate into SF by the two administration routes, and the permeation ratios were approximately 1:3. The AUC0-∞ and Cmax were lower with electroporation compared with systemic administration, but the CSF /CPlasma (concentration of sinomenine in SF vs that of plasma) at 90, 120, 150, 180, 240 and 480 min by electroporation was 3- to 10-fold higher relative to systemic administration. This illustrated that sinomenine can be targeted into joints by electroporation, and electroporation is a potential technique for sinomenine's transdermal delivery.

  5. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis.

    Science.gov (United States)

    Komatsu, Noriko; Okamoto, Kazuo; Sawa, Shinichiro; Nakashima, Tomoki; Oh-hora, Masatsugu; Kodama, Tatsuhiko; Tanaka, Sakae; Bluestone, Jeffrey A; Takayanagi, Hiroshi

    2014-01-01

    Autoimmune diseases often result from an imbalance between regulatory T (Treg) cells and interleukin-17 (IL-17)-producing T helper (TH17) cells; the origin of the latter cells remains largely unknown. Foxp3 is indispensable for the suppressive function of Treg cells, but the stability of Foxp3 has been under debate. Here we show that TH17 cells originating from Foxp3(+) T cells have a key role in the pathogenesis of autoimmune arthritis. Under arthritic conditions, CD25(lo)Foxp3(+)CD4(+) T cells lose Foxp3 expression (herein called exFoxp3 cells) and undergo transdifferentiation into TH17 cells. Fate mapping analysis showed that IL-17-expressing exFoxp3 T (exFoxp3 TH17) cells accumulated in inflamed joints. The conversion of Foxp3(+)CD4(+) T cells to TH17 cells was mediated by synovial fibroblast-derived IL-6. These exFoxp3 TH17 cells were more potent osteoclastogenic T cells than were naive CD4(+) T cell-derived TH17 cells. Notably, exFoxp3 TH17 cells were characterized by the expression of Sox4, chemokine (C-C motif) receptor 6 (CCR6), chemokine (C-C motif) ligand 20 (CCL20), IL-23 receptor (IL-23R) and receptor activator of NF-κB ligand (RANKL, also called TNFSF11). Adoptive transfer of autoreactive, antigen-experienced CD25(lo)Foxp3(+)CD4(+) T cells into mice followed by secondary immunization with collagen accelerated the onset and increased the severity of arthritis and was associated with the loss of Foxp3 expression in the majority of transferred T cells. We observed IL-17(+)Foxp3(+) T cells in the synovium of subjects with active rheumatoid arthritis (RA), which suggests that plastic Foxp3(+) T cells contribute to the pathogenesis of RA. These findings establish the pathological importance of Foxp3 instability in the generation of pathogenic TH17 cells in autoimmunity.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  7. Synovial sarcoma presenting as iliotibial band friction syndrome.

    Science.gov (United States)

    Mesiha, Mena; Bauer, Thomas; Andrish, Jack

    2009-10-01

    Iliotibial band friction syndrome is a common entity that is often quickly diagnosed in orthopedic clinics. However, synovial sarcoma is an elusive clinical entity that appears around many joints with variable presentations. This case report is an example of a patient with a classic presentation of iliotibial band friction syndrome that was diagnosed as a synovial sarcoma on further investigation.

  8. 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.

  9. Effect of raloxifene on arthritis and bone mineral density in rats with collagen-induced arthritis.

    Science.gov (United States)

    Hayashi, Ikuta; Hagino, Hiroshi; Okano, Toru; Enokida, Makoto; Teshima, Ryota

    2011-02-01

    We studied the effect of raloxifene (RAL) on arthritis and bone mineral density (BMD) in rats with collagen-induced arthritis (CIA). Seven-month-old female Sprague-Dawley rats were divided into five groups: rats without CIA (CNT), CIA rats that underwent ovariectomy (OVX) and were treated with RAL (CIA + OVX + RAL), CIA rats that underwent OVX and were treated with vehicle (CIA + OVX + Veh), CIA rats that had sham surgery and were treated with RAL (CIA + sham + RAL), and CIA rats that had sham surgery and were treated with vehicle (CIA + sham + Veh). RAL was orally administered at 10 mg/kg every day for 3 weeks, beginning 1 week after initial sensitization until death at 4 weeks. Every week until death, we evaluated hind paw thickness and arthritis score. BMD was measured by peripheral quantitative computed tomography at the distal metaphysis and the diaphysis of the femur; we also performed histomorphometry of the proximal tibia and histological evaluation of arthritis. RAL administration suppressed hind paw thickness and arthritis score and prevented decreases in BMD and cortical thickness. In the histomorphometric analysis, bone-resorption parameters were significantly lower in the RAL groups than in the Veh groups. RAL significantly inhibited synovial proliferation in CIA rats. RAL effects on arthritis and bone were apparent regardless of whether an animal had undergone OVX. RAL could suppress arthritis and bone loss in estrogen-replete or -depleted rats. These findings, using an animal model, indicate the potential usefulness of RAL as an effective treatment for premenopausal RA patients as well as postmenopausal ones.

  10. Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis.

    Science.gov (United States)

    Heftdal, Line Dam; Andersen, Thomas; Jæhger, Ditte; Woetmann, Anders; Østgård, René; Kenngott, Elisabeth E; Syrbe, Uta; Sieper, Joachim; Hvid, Malene; Deleuran, Bent; Kragstrup, Tue W

    2017-04-02

    Spondyloarthritis (SpA) is characterized by inflammation and new bone formation and can be treated by inhibition of the proinflammatory cytokines TNF-α and IL-17A. IL-26 is considered a proinflammatory cytokine, predominantly related to Th17 cells. In the present study, we investigate IL-26 expression in SpA patients, and examine the in vitro production of IL-26 by synovial cells and the effects of IL-26 on human osteoblasts. IL-26 was measured by ELISA in plasma and synovial fluid (SF) of 15 SpA patients and in plasma samples from 12 healthy controls. Facet joints from axial SpA patients were stained for IL-26 and analyzed by fluorescence microscopy. Synovial fluid mononuclear cells, C-C motif chemokine receptor 6 memory Th17 cells, and fibroblast-like synoviocytes (FLSs) were isolated, and supernatants were analyzed for IL-26 content by ELISA. FLSs were further stained for IL-26 production and the myofibroblast marker α-smooth-muscle-actin (αSMA) and analyzed by flow cytometry. Human osteoblasts were cultured in the presence of IL-26, and the degree of mineralization was quantified. We found that IL-26 levels in SF were increased compared with plasma (P < 0.0001). Moreover, IL-26 expression was found in facet joints of axial SpA patients within the bone marrow. IL-26 secretion was primarily found in αSMA(+) myofibroblasts. In contrast, Th17 cells did not produce detectable amounts of IL-26. Human osteoblasts treated with IL-26 showed increased mineralization compared with untreated osteoblasts (P = 0.02). In conclusion, IL-26 seems to be produced by myofibroblasts in the inflamed synovium and could be a possible facilitator of bone mineralization in SpA.

  11. MRI findings of treated bacterial septic arthritis

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  12. Arthritis of the Hand

    Science.gov (United States)

    .org Arthritis of the Hand Page ( 1 ) The hand and wrist have multiple small joints that work together to ... a shoelace. When the joints are affected by arthritis, activities of daily living can be difficult. Arthritis ...

  13. Calcium pyrophosphate arthritis

    Science.gov (United States)

    ... are similar, CPPD arthritis can be confused with: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis Exams and Tests Most arthritic ... A.M. Editorial team. Related MedlinePlus Health Topics Gout Browse the Encyclopedia A.D.A.M., Inc. ...

  14. Diff-Quik® staining method for detection and identification of monosodium urate and calcium pyrophosphate crystals in synovial fluids

    Directory of Open Access Journals (Sweden)

    M. Hammoud

    2011-09-01

    Full Text Available The aim of this study was to evaluate whether DQ could prove useful to identify monosodium urate (MSU and calcium pyrophosphate dehydrate (CPPD crystals on permanent mounted stained slides. To this end, we studied 27 synovial fluid (SF samples obtained from the knees of patients with the pseudogout (n=21 and acute gouty arthritis (n=6. Wet analysis for crystal detection and identification was performed within one hour of joint aspiration. In addition, we studied 16 inflammatory synovial effusions obtained from patients with knee arthritis not induced by crystals. For each SF, DQ stained slides were analyzed by 2 experienced doctors in SF analysis. The observers were blinded to the type of crystal present in the SF. Each slide was analyzed by compensated polarized and transmitted light microscopy. SF was considered positive if intracellular and/or extracellular crystals were clearly identified. In addition, the observers were asked to identify the type of the crystals using compensated polarized light microscopy. Sensitivity, specificity, accuracy, positive predictive value (PPV, and negative predictive value (NPV of the DQ staining method were determined. 51 true positive and 28 true negative specimens were correctly classified (39 CPPD samples, 12 MSU samples, and 28 samples of crystals-unrelated arthropathies. All MSU specimens were correctly diagnosed.

  15. Epidemiology of septic arthritis of the knee at Hospital das Clinicas, Universidade de Sao Paulo

    Directory of Open Access Journals (Sweden)

    Camilo Partezani Helito

    2014-01-01

    Full Text Available Background: Septic arthritis is an infrequent disease although very important due to the possibility of disastrous outcomes if treatment is not adequately established. Adequate information concerning the epidemiology of septic arthritis is still lacking due to the uncommon nature of the disease as well as the struggle to establish a correct case-definition. Objective: To epidemiologically characterize the population seen at Hospital das Clínicas, University of São Paulo with a diagnosis of septic arthritis between 2006 and 2011. Methods: Sixty-one patients diagnosed with septic arthritis of the knee between 2006 and 2011 were retrospectively evaluated. The patients' clinical and epidemiological characteristics, the microorganisms that caused the infection and the patients' treatment and evolution were analyzed. Results: Septic arthritis of the knee was more common among men, with distribution across a variety of age ranges. Most diagnoses were made through positive synovial fluid cultures. The most prevalent clinical comorbidities were systemic arterial hypertension and diabetes mellitus, and the most commonly reported joint disease was osteoarthritis. Staphylococcus aureus was the prevailing pathogen. Fever was present in 36% of the cases. All patients presented elevation in inflammatory tests. Gram staining was positive in only 50.8% of the synovial fluid samples analyzed. Six patients presented complications and unfavorable evolution of their condition. Conclusion: S. aureus is still the most common pathogen in acute knee infections in our environment. Gram staining, absence of fever and normal leukocyte count cannot be used to rule out septic arthritis.

  16. Primary Synovial Sarcoma of the Kidney

    Directory of Open Access Journals (Sweden)

    Takashi Kawahara

    2009-10-01

    Full Text Available The case was a 40-year-old female. She visited a local doctor with a chief complaint of right side abdominal pain. A right kidney tumor measuring 10 cm in diameter was observed in an abdominal Computed Tomography (CT scan. Based on the CT image, the possibility of angiomiolipoma (AML could not be ruled out, but a high maximum standardized uptake value (SUVmax of 7.8 was observed in a Positron Emission Tomography CT (PET-CT scan and there was a possibility of malignancy. We therefore performed a transperitoneal right radial nephrectomy. Although adhesion of the tumor to the duodenum and the inferior vena cava was observed, it was possible to perform an excision. The tumor accounted for a large proportion of the excised kidney; the surrounding areas had taken on a cyst-like structure, and the interior comprised grayish brittle tissue exhibiting solid growth. Histologically, gland-like and cyst-like structures composed of cylindrical cuboidal cells and mainly characterized by the solid growth of short fusiform-shaped and oval-shaped basophilic cells were observed, and we believed it was a synovial sarcoma. There were no malignant findings in the adrenal gland. There have been approximately 30 reported cases around the world of synovial sarcoma that developed in the kidney, and we herein report this case with bibliographic considerations.

  17. Synovial chondromatosis of the temporomandibular joint.

    Science.gov (United States)

    Reyes Macías, Juan Francisco; Sánchez Prieto, Martín

    2007-01-01

    Synovial Chondromatosis (SC) is a disease whose etiology is unknown, can be defined as a benign synovial process characterized by the formation of metaplastic cartilaginous nodes inside connective tissue of articular surfaces, is considered an active metaplastic phenomenon better than a neoplastic process; it presents a greater preference to affect women who constitute almost 70% of reported cases, the age range is wide and oscillates between 18-75 years (average 44.6 years). Between the main clinical findings are: pain, crackle, volume augmentation and a limited buccal opening. SC is an unusual state and the reports in the English literature are no more than 75 cases, only 66 of those where histologically verified, most of those were affecting great joints like hip, knee and shoulder, but if SC is not frequent in this sites, is even more infrequent on temporomandibular joint. The aim of this paper is to report a clinical case and at the same time to realize a brief review of the literature.

  18. Versican Expression during Synovial Joint Morphogenesis

    Directory of Open Access Journals (Sweden)

    John B. Shepard, Heidi A. Krug, Brooklynn A. LaFoon, Stanley Hoffman, Anthony A. Capehart

    2007-01-01

    Full Text Available The extracellular matrix (ECM plays a critical role in governing cell behavior and phenotype during limb skeletogenesis. Chondroitin sulfate proteoglycans (Cspgs are highly expressed in the ECM of precartilage mesenchymal condensations and are important to limb chondrogenesis and cartilage structure, but little is known regarding their involvement in formation of synovial joints in the embryonic limb. Matrix versican Cspg expression has previously been reported in the epiphysis of developing long bones and presumptive joint; however, detailed analysis has not yet been conducted. In the present study we immunolocalized versican and aggrecan Cspgs during chick elbow joint morphogenesis between HH st25-41 of development. In this study we show that versican and aggrecan expression initially overlapped in the incipient cartilage model of long bones in the wing, but versican was also highly expressed in the perichondrium and presumptive joint interzone during early stages of morphogenesis (HH st25-34. By HH st36-41 versican localization was restricted to the future articular surfaces of the developing joint and surrounding joint capsule while aggrecan localized in an immediately adjacent and predominately non-overlapping region of chondrogenic cells at the epiphyses. These results suggest a potential role for versican proteoglycan in development and maintenance of the synovial joint interzone.

  19. Increased IL-20 and IL-24 target osteoblasts and synovial monocytes in spondyloarthritis.

    Science.gov (United States)

    Kragstrup, Tue Wenzel; Andersen, Morten Nørgaard; Schiøttz-Christensen, Berit; Jurik, Anne Grethe; Hvid, Malene; Deleuran, Bent

    2017-04-02

    The pathogenesis of spondyloarthritis (SpA) involves activation of the innate immune system, inflammation and new bone formation. The two cytokines IL-20 and IL-24 have been shown to link innate immune activation and tissue homeostasis. We hypothesized that these two cytokines are secreted as part of activation of the innate immune system and affect bone homeostasis in SpA. IL-20 and IL-24 were measured in plasma from axial SpA patients (n=83). Peripheral SpA patients (n=16) were included for in vitro cell culture studies. The plasma IL-20 and IL-24 levels were increased in SpA patients compared with healthy controls (HCs) by 57% and 83%, respectively (both p<0.0001). The Toll like receptor 4 induced secretion of the two cytokines was greater in SpA peripheral blood mononuclear cells (PBMCs) compared with HC PBMCs. IL-20 and IL-24 increased the production of monocyte chemo attractant protein-1 by activated SpA synovial fluid monocytes, decreased the production of dickkopf-1 by SpA fibroblast-like synovial cells and induced mineralization in human osteoblasts. Taken together, our findings indicate disease-aggravating functions of IL-20 and IL-24 in SpA. This article is protected by copyright. All rights reserved.

  20. 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.

  1. Rheumatoid arthritis.

    Science.gov (United States)

    Smolen, Josef S; Aletaha, Daniel; McInnes, Iain B

    2016-10-22

    Rheumatoid arthritis is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterised risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and use of conventional, biological, and newz non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favourable, many still do not respond to current therapies. Accordingly, new therapies are urgently required. In this Seminar, we describe current insights into genetics and aetiology, pathophysiology, epidemiology, assessment, therapeutic agents, and treatment strategies together with unmet needs of patients with rheumatoid arthritis.

  2. Ureaplasma septic arthritis in an immunosuppressed patient with juvenile idiopathic arthritis.

    Science.gov (United States)

    George, Michael David; Cardenas, Ana Maria; Birnbaum, Belinda K; Gluckman, Stephen J

    2015-06-01

    Mycoplasmas, including Ureaplasma and Mycoplasma species, are uncommon but important causes of septic arthritis, especially affecting immunosuppressed patients. Many of the reported cases have been associated with congenital immunodeficiency disorders, especially hypogammaglobulinemia. Mycoplasmas are difficult to grow in the laboratory, and these infections may be underdiagnosed using culture techniques. We report a case of a 21-year-old woman with juvenile idiopathic arthritis and hip arthroplasties treated with rituximab and adalimumab who developed urogenital infections and soft tissue abscesses followed by knee arthritis with negative routine cultures. Ureaplasma species was identified from synovial fluid on 2 separate occasions using a broad-range 16S ribosomal RNA gene polymerase chain reaction. Azithromycin led to rapid improvement in symptoms, but after completion of therapy, involvement of the hip prosthesis became apparent, and again, 16S rRNA gene polymerase chain reaction was positive for Ureaplasma species. The literature is reviewed with a discussion of risk factors for Mycoplasma septic arthritis, clinical presentation, methods of diagnosis, and treatment.

  3. 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.

  4. Extra-articular Synovial Chondromatosis Eroding and Penetrating the Acromion

    Science.gov (United States)

    El Rassi, George; Matta, Jihad; Hijjawi, Ayman; Khair, Ousama Abou; Fahs, Sara

    2015-01-01

    Synovial chondromatosis of the shoulder is an uncommon disorder. It usually affects the glenohumeral joint and is characterized by metaplasia of the synovium leading to the formation of osteochondral loose bodies. Few cases of extra-articular subacromial synovial chondromatosis involving the rotator cuff tendon have been reported in the literature. The treatment of previously reported cases consisted of open bursectomy and removal of loose bodies. We report a case of subacromial synovial chondromatosis without rotator cuff involvement but with severe erosion and fracture of the acromion. Treatment consisted of shoulder arthroscopy to remove all loose bodies, total bursectomy, and debridement of the acromion. Potential benefits of arthroscopy were also evaluated. PMID:26697302

  5. Primary mediastinal giant synovial sarcoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Gaetano Rea

    2015-03-01

    Full Text Available Synovial sarcoma has been defined by the World Health Organization (WHO in 2002 as a type of mesenchymal tissue cell tumor that exhibits epithelial differentiation and represents the third most common soft-tissue sarcoma in adults, accounting for approximately 10% of soft-tissue sarcomas. To date, only few reports have focused on mediastinal synovial sarcoma imaging findings. Herein, we report a case of a 13 cm primary mediastinal giant synovial sarcoma, diagnosed in a 56-year-old patient admitted in our Department of Radiology with a six-month history of dyspnea and back pain.

  6. Ultrasonographic findings of septic arthritis and osteomyelitis in neonatal hip

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hoon; Jung, Kun Sik; Koh, Jung Kon; Im, Myung Ah; Kwon, Kwi Ryun; Kim, Sung Soo [Pohang Sunlim Hospital, Handong University, Pohang (Korea, Republic of)

    2000-06-15

    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.

  7. Septic arthritis in the temporomandibular joint

    Directory of Open Access Journals (Sweden)

    Hassan Mahdi Al-Khalisy

    2015-01-01

    Full Text Available Septic arthritis of the temporomandibular joint (TMJ is a rare event that has only been reported a few dozen times worldwide. This case is remarkable for septic arthritis of the TMJ joint in an otherwise healthy male. Case Report: A 24-year-old male presented to the emergency department with periauricular swelling, erythema, fever, myalgia′s and generalized joint pain. He had previously sought medical attention and was placed on ciprofloxacin. However, he developed facial swelling and a rash and had to discontinue the antibiotic. On physical exam the patient had a large swelling and tenderness in his left periauricular area, with erythema and deviation of the right mandible which limited his ability to open the mouth. A computed tomography showed mild asymmetric soft tissue swelling in the left pharyngeal region but did not show joint effusion. Subsequent magnetic resonance imaging did show effusion of the joint space. The effusion was drained, and the synovial fluid was submitted for gram stain, culture, and sensitivity. The cultures grew menthicillin sensitive Staphyloccocus Aureus. The patient was discharged to complete a two week course of intravenous (IV Ceftriaxone and IV Vancomycin via home infusion. Conclusion: Septic Arthritis of the TMJ is a rare event with very specific clinical symptoms. Due to the low sensitivity of the computed tomography scan, magnetic resonance imaging should be considered when computed tomography scan is negative for TMJ effusion.

  8. Septic arthritis in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Al-Ahaideb Abdulaziz

    2008-07-01

    Full Text Available Abstract There is an increasing number of rheumatoid patients who get septic arthritis. Chronic use of steroids is one of the important predisposing factors. The clinical picture of septic arthritis is different in immunocompromised patients like patients with rheumatoid arthritis. The diagnosis and management are discussed in this review article.

  9. Septic arthritis in patients with rheumatoid arthritis

    OpenAIRE

    Al-Ahaideb Abdulaziz

    2008-01-01

    Abstract There is an increasing number of rheumatoid patients who get septic arthritis. Chronic use of steroids is one of the important predisposing factors. The clinical picture of septic arthritis is different in immunocompromised patients like patients with rheumatoid arthritis. The diagnosis and management are discussed in this review article.

  10. LABORATORY FINDINGS IN PSORIATIC ARTHRITIS

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-09-01

    Full Text Available Psoriatic arthritis (PsA has been classically defined as an inflammatory arthritis associated with psoriasis. However, in comparison with other relevant inflammatory arthropathies, in which a definite diagnosis is frequently possible only by means of laboratory investigations, in PsA true laboratory diagnostic markers are lacking. Some markers are utilised more to differentiate other diseases than to characterise PsA. For example in polyarticular PsA, which may be in some cases indistinguishable from RA, the rheumatoid factor (RF or the more specific and recently introduced antibodies to cyclic citrullinated peptides (anti-CCP, may be useful to better identify RA. However, RF was found in 5% to 13% of patients with PsA, and anti-CCP may be observed in almost similar percentage. The determination of ESR and/or CRP is frequently disappointing in PsA, since they are both elevated in only half of the patients with PsA. However, ESR and/or CRP are included in the most utilised response criteria for RA, such as ACR and DAS, and, in addition are also considered reliable in the assessment of PsA. Furthermore, elevated levels of ESR have been proposed as one of the best predictors of damage progression and, in addition, a low ESR seems protective, while an ESR >15 mm/h is one of the factors associated with an increased mortality in PsA. The synovial fluid (SF effusion is much higher in PsA, in comparison with other arthropathies. When available, SF analysis may offer additive information useful for the diagnosis, such as the increased number of leukocytes, which underlines the inflammatory nature of the effusion even in a patient with normal serum levels of acute phase response. We found that elevated IL-1 levels in SF of patients with early disease (<6 months, may be predictive of an evolution in polyarticular form at follow-up. This observation is in keeping with the crucial role that inflammatory cytokines play in PsA, probably related to a genetic

  11. Sensitivities of PCR, MicroTrak, ChlamydiaEIA, IDEIA, and PACE 2 for purified Chlamydia trachomatis elementary bodies in urine, peripheral blood, peripheral blood leukocytes, and synovial fluid.

    OpenAIRE

    Kuipers, J G; Scharmann, K; Wollenhaupt, J; Nettelnbreker, E; Hopf, S.; Zeidler, H

    1995-01-01

    Routine microbiological diagnosis of Chlamydia-induced reactive arthritis is based mainly on the detection of Chlamydia trachomatis with urogenital swabs or in urine. Because chlamydial antigen, rRNA, and DNA are present in low quantities in the inflamed joint, highly sensitive assays are needed to detect C. trachomatis not only at the primary site of infection but also in peripheral blood and peripheral blood leukocytes, which are suspected carriers for dissemination, and in synovial fluid. ...

  12. /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.

  13. Tribological and electrochemical studies on biomimetic synovial fluids

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In this study, tribological and electrochemical performances of the new biomimetic synovial fluids were studied according to different composition concentrations, including hyaluronic acid, albumin and alendronic acid sodium. By using Taguchi method, the composition contents of the biomimetic synovial fluids were designed. Items such as friction coefficient, mean scar diameter and viscosity were investigated via a four-ball tribo-tester, viscosity meter and optical microscope. Polarization studies were carried out to analyze the electrochemical behaviour of the fluids. Results showed that hyaluronic acid dominates the viscosity of the fluids. High albumin concentration will reduce friction, while increasing wear rate due to the electro-chemical effect. Alendronic acid sodium is found to reduce the biocorrosion of CoCrMo as well as provide better lubricating. In conclusion, biomimetic synovial fluids partially recover the functions of natural synovial fluids and provide good lubricating property.

  14. Inhibition of Inflammation and Bone Erosion by RNA Interference-Mediated Silencing of Heterogeneous Nuclear RNP A2/B1 in Two Experimental Models of Rheumatoid Arthritis

    NARCIS (Netherlands)

    Herman, S.; Fischer, A.; Presumey, J.; Hoffmann, M.; Koenders, M.I.; Escriou, V.; Apparailly, F.; Steiner, G.

    2015-01-01

    OBJECTIVE: The nuclear protein heterogeneous nuclear RNP A2/B1 (hnRNP A2/B1) is involved in posttranscriptional regulation of gene expression. It is constitutively expressed in lymphoid organs and highly up-regulated in the synovial tissue of patients with rheumatoid arthritis (RA), who may also gen

  15. Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology

    DEFF Research Database (Denmark)

    Volck, B; Johansen, J S; Stoltenberg, M;

    2001-01-01

    OBJECTIVE: The presence of YKL-40 (human cartilage glycoprotein 39) in synovium, cartilage and synovial fluid (SF) from knee joints of patients with rheumatoid arthritis and osteoarthritis (OA) were related to histopathological changes in synovium and cartilage and to serum YKL-40 and other bioch...

  16. Magnetic resonance imaging, radiography, and scintigraphy of the finger joints: one year follow up of patients with early arthritis. The TIRA Group

    DEFF Research Database (Denmark)

    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...

  17. Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte death and matrix-metalloproteinase-mediated cartilage matrix degradation despite enhanced joint inflammation.

    NARCIS (Netherlands)

    Nabbe, K.C.A.M.; Lent, P.L.E.M. van; Holthuysen, A.E.M.; Sloetjes, A.W.; Koch, A.E.; Radstake, T.R.D.J.; Berg, W.B. van den

    2005-01-01

    During immune-complex-mediated arthritis (ICA), severe cartilage destruction is mediated by Fcgamma receptors (FcgammaRs) (mainly FcgammaRI), cytokines (e.g. IL-1), and enzymes (matrix metalloproteinases (MMPs)). IL-13, a T helper 2 (Th2) cytokine abundantly found in synovial fluid of patients with

  18. Within-day variation and influence of physical exercise on circulating Galectin-3 in patients with rheumatoid arthritis and healthy individuals

    DEFF Research Database (Denmark)

    Issa, S F; Christensen, A F; Lottenburger, T;

    2015-01-01

    Galectin-3 has been suggested as a pro-inflammatory mediator in rheumatoid arthritis (RA). Previous studies have reported overexpression of Galectin-3 in RA synovitis and increased levels in synovial fluid and serum in long-standing RA compared with osteoarthritis and healthy controls. Our object...

  19. Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

    Directory of Open Access Journals (Sweden)

    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.

  20. The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Otkjaer, Kristian; Holm, Christian

    2008-01-01

    chemoattractant protein 1 (CCL2/MCP-1) secretion, but not tumour necrosis factor alpha mRNA synthesis or IL-6 secretion. Both IL-20 and IL-24 showed correlations to CCL2/MCP-1 in plasma from rheumatoid arthritis and spondyloarthropathy patients. This study associates IL-20 and IL-24 to the synovium of rheumatoid...... whereas IL-24 protein was observed in endothelial cells and mononuclear cells. IL-20 receptor type 1 and IL-22 receptor were expressed by granulocytes in the synovial fluid. In synovial fluid mononuclear cell cultures, stimulation with recombinant human IL-20 or recombinant human IL-24 induced monocyte...

  1. A pathogenetic study of the early connective tissue lesions of viral caprine arthritis-encephalitis.

    OpenAIRE

    Adams, D. S.; Crawford, T B; Klevjer-Anderson, P

    1980-01-01

    Experiments were designed to correlate morphologic lesions with the presence of caprine arthritis-encephalitis virus (CAEV). Twenty-one cesarean-derived goat kids were infected with 10(6) to 10(7) TCID50 of virus, killed sequentially, and examined for viral antigens by immunofluorescence, viral infectivity by isolation and titration, and morphologic changes by light microscopy. Fluorescent viral antigens were detected from 1 to 10 days postinoculation (DPI) and only in synovial cells. Virus w...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. Color Doppler ultrasound of the hand: observations on clinical utility in rheumatoid arthritis.

    Science.gov (United States)

    Saadeh, Constantine; Gaylor, Patrick; Lee, Doohi; Malacara, Jan; Gaylor, Michael

    2004-02-01

    The use of ultrasound with color Doppler in the evaluation of rheumatoid arthritis was followed in 25 patients with joint complaints. Small joint ultrasound of the metacarpophalangeal joints (MCPs) as well as the wrists was performed with supplementation by color Doppler. In addition, 6 patients were followed for at least 3 months after start of treatment of rheumatoid arthritis using the same technique. In patients with what appeared to be definite rheumatoid arthritis, ultrasound supported this diagnosis as evidenced by the finding of cortical defects, extensor tendon sheath thickening, and synovial proliferation. Increased activity by color Doppler ultrasonography was the most common finding. Significant decrease in color Doppler activity was noted in the 6 patients who were followed up after 3 months of therapy with disease-modifying agents. Therefore, the use of ultrasound with color Doppler could aid in the diagnosis and follow up of patients with rheumatoid arthritis.

  4. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

    Science.gov (United States)

    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.

  5. Septic arthritis in a lumbar facet joint: a rare cause of an epidural abscess

    Energy Technology Data Exchange (ETDEWEB)

    Heenan, S.D. [Dept. of Neuroradiology, Atkinson Morley`s Hospital, London (United Kingdom); Britton, J. [Dept. of Neuroradiology, Atkinson Morley`s Hospital, London (United Kingdom)

    1995-08-01

    A 10-year-old boy presented with a 7-day history of back pain and pyrexia. MRI showed an epidural abscess arising from septic arthritis in a lumbar facet joint. To our knowledge, there are only two previously reported cases of septic arthritis of a facet joint leading to an epidural abscess. This case illustrates how infection in a synovial joint may extend into the extradural space and might be the route of infection in more cases than has previously been recognised. (orig.)

  6. A pathogenetic study of the early connective tissue lesions of viral caprine arthritis-encephalitis.

    Science.gov (United States)

    Adams, D S; Crawford, T B; Klevjer-Anderson, P

    1980-05-01

    Experiments were designed to correlate morphologic lesions with the presence of caprine arthritis-encephalitis virus (CAEV). Twenty-one cesarean-derived goat kids were infected with 10(6) to 10(7) TCID50 of virus, killed sequentially, and examined for viral antigens by immunofluorescence, viral infectivity by isolation and titration, and morphologic changes by light microscopy. Fluorescent viral antigens were detected from 1 to 10 days postinoculation (DPI) and only in synovial cells. Virus was reisolated from several joints and from brain 0.5 to 79 DPI. Increases in synovial fluid cell counts were noted by 1 DPI, and morphologic changes in synovial membranes were present from 3 to 45 DPI. Joint lesions progressed from mild synovial cell hyperplasia and perivascular mononuclear cell infiltration to severe synovial cell hyperplasia and mononuclear cell infiltration with villous hypertrophy. Lesions elsewhere were mild, consisting only of perivascular mononuclear cell infiltrates. Eleven cesarean-derived control goats were negative for viral antigens, virus, and morphologic lesions.

  7. Regional limb perfusion for antibiotic treatment of experimentally induced septic arthritis.

    Science.gov (United States)

    Whithair, K J; Bowersock, T L; Blevins, W E; Fessler, J F; White, M R; Van Sickle, D C

    1992-01-01

    Septic arthritis was induced in one antebrachiocarpal joint of seven horses by the intra-articular injection of 1 mL Staphylococcus aureus suspension containing a mean of 10(5) colony-forming units. Twenty-four hours after inoculation, four horses were treated by regional perfusion with 1 g of gentamicin sulfate, and three horses received 2.2 mg/kg gentamicin sulfate intravenously (IV) every 6 hours. Synovial fluid was collected for culture and cytology at regular intervals, and the synovial membranes were collected for culture and histologic examination at euthanasia 24 hours after the first treatment. Gentamicin concentration in the septic synovial fluid after three successful perfusions was 221.2 +/- 71.4 (SD) micrograms/mL; after gentamicin IV, it was 7.6 +/- 1.6 (SD) micrograms/mL. The mean leukocyte count in the inoculated joints decreased significantly by hour 24 in the successfully perfused joints. Terminal bacterial cultures of synovial fluid and synovial membranes were negative in two horses with successfully perfused joints. S. aureus was isolated from the infected joints in all three horses treated with gentamicin IV.

  8. Observations on Arthritis in Broiler Breeder Chickens Experimentally Infected with Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Chang-Qin Gu§, Xue-Ying Hu§, Chang-Qing Xie1, Wan-Po Zhang, De-Hai Wang, Quan Zhou and Guo-Fu Cheng1*

    2013-04-01

    Full Text Available Staphylococcus aureus is the most common cause of bacterial arthritis in broiler breeder chickens. In this study, we established a model of broiler breeder chicken arthritis inoculated with Staph. aureus isolated from a spontaneously occurring bacterial arthritis in chickens. We evaluated the model by bacteriology, serology, pathology, and immunology. The results showed that 2.5 × 109 cfu Staph. aureus injected into the right joint cavity can successfully induce a chicken arthritis model. The majority of the infected chickens suffered lameness and joint swelling at 3 days post-inoculation (DPI. The death peak time was on 7 DPI and the mortality rate was 51.1%. Staph. aureus can be continuously isolated from the blood and left joint synovial fluid of the infected chickens. Lesions found on the infected chickens consisted of swollen joints full of caseous exudates, cartilage injury, and synovial membrane thickening with infiltration of inflammatory cells. The center of the lesion contained many round bacterial cocci. With joint injury aggravation, intra-articular hyaluronic acid gradually decreased, and serum interleukin-6 became significantly higher compared with the control (P<0.01 from 3 DPI. The results indicated that the chicken models of Staph. aureus-mediated arthritis were successful, and can be used to gain a better understanding of the host-bacterium relationship.

  9. Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis.

    Science.gov (United States)

    Willis, V C; Banda, N K; Cordova, K N; Chandra, P E; Robinson, W H; Cooper, D C; Lugo, D; Mehta, G; Taylor, S; Tak, P P; Prinjha, R K; Lewis, H D; Holers, V M

    2017-01-27

    Citrullination of joint proteins by the protein arginine deiminase (PAD) family of enzymes is recognized increasingly as a key process in the pathogenesis of rheumatoid arthritis. This present study was undertaken to explore the efficacy of a novel PAD4-selective inhibitor, GSK199, in the murine collagen-induced arthritis model of rheumatoid arthritis. Mice were dosed daily from the time of collagen immunization with GSK199. Efficacy was assessed against a wide range of end-points, including clinical disease scores, joint histology and immunohistochemistry, serum and joint citrulline levels and quantification of synovial autoantibodies using a proteomic array containing joint peptides. Administration of GSK199 at 30 mg/kg led to significant effects on arthritis, assessed both by global clinical disease activity and by histological analyses of synovial inflammation, pannus formation and damage to cartilage and bone. In addition, significant decreases in complement C3 deposition in both synovium and cartilage were observed robustly with GSK199 at 10 mg/kg. Neither the total levels of citrulline measurable in joint and serum, nor levels of circulating collagen antibodies, were affected significantly by treatment with GSK199 at any dose level. In contrast, a subset of serum antibodies reactive against citrullinated and non-citrullinated joint peptides were reduced with GSK199 treatment. These data extend our previous demonstration of efficacy with the pan-PAD inhibitor Cl-amidine and demonstrate robustly that PAD4 inhibition alone is sufficient to block murine arthritis clinical and histopathological end-points.

  10. A Case of Polyarticular Pasteurella multocida Septic Arthritis.

    Science.gov (United States)

    Nitoslawski, Sarah; McConnell, Todd M; Semret, Makeda; Stein, Michael A

    2016-01-01

    A 76-year-old man with a history of osteoarthritis presents with right leg erythema and inability to weight-bear and pain in his right shoulder. Synovial fluid cell count of the knee and shoulder showed abundant neutrophils, and cultures of the knee showed growth of Pasteurella multocida. The patient owned four cats with which he had frequent contact, but history and physical examination elicited no evidence of scratches or bites. This case highlights the invasive potential of Pasteurella multocida in an immunocompetent individual and its capacity to cause septic arthritis in the setting of frequent animal contact.

  11. A Case of Polyarticular Pasteurella multocida Septic Arthritis

    Directory of Open Access Journals (Sweden)

    Sarah Nitoslawski

    2016-01-01

    Full Text Available A 76-year-old man with a history of osteoarthritis presents with right leg erythema and inability to weight-bear and pain in his right shoulder. Synovial fluid cell count of the knee and shoulder showed abundant neutrophils, and cultures of the knee showed growth of Pasteurella multocida. The patient owned four cats with which he had frequent contact, but history and physical examination elicited no evidence of scratches or bites. This case highlights the invasive potential of Pasteurella multocida in an immunocompetent individual and its capacity to cause septic arthritis in the setting of frequent animal contact.

  12. Effects of methotrexate on cell proliferation and cell cycle of synovial fibroblasts in patients with rheumatoid arthritis%甲氨蝶呤对类风湿关节炎滑膜细胞增生及细胞周期的影响

    Institute of Scientific and Technical Information of China (English)

    刘巧红; 沈凌汛; 滕云; 王慧; 陈燕; 杨真荣

    2004-01-01

    目的研究甲氨蝶呤(MTX)对类风湿关节炎(RA)滑膜细胞增生及细胞周期的影响,揭示MTX治疗RA的机制.方法应用四唑氮化合物(MTS)/黄嘌呤氧化酶(PMS)比色法和流式细胞术分别测定MTX处理和未处理RA患者滑膜细胞的细胞增生水平和细胞周期.结果加入不同浓度MTX(0.2~2 μmol/L),RA患者滑膜细胞接种后第4天起增生水平均显著低于未处理的RA患者滑膜细胞(P<0.05);细胞周期分析显示加入不同浓度MTX(0.2~2 μmol/L)后第5、8天,RA患者滑膜细胞停留在G1期的比例要比未处理的RA患者滑膜细胞明显增加(P<0.05),而S、G2期的细胞比例比未处理的RA患者滑膜细胞则明显减少(P<0.05);MTX能以剂量依赖性明显抑制滑膜细胞的增生水平.结论MTX在治疗RA时,主要起到对RA患者滑膜细胞的增生及增生相关病理过程的抑制.

  13. Sonic hedgehog (SHH) promotes the proliferation of synovial fibroblasts of rats with collagen-induced arthritis%Sonic Hedgehog(SHH)促进胶原蛋白诱导关节炎大鼠滑膜成纤维细胞的增殖

    Institute of Scientific and Technical Information of China (English)

    李慧; 秦苏萍; 孙德旭; 潘伟; 李向阳; 孔凡运; 郑葵阳; 汤仁仙

    2016-01-01

    目的 探讨Sonic Hedgehog(SHH)在滑膜成纤维细胞增殖中的作用.方法 收集类风湿性关节炎(RA)、系统性红斑狼疮(SLE)、强直性脊柱炎(AS)患者及健康正常人血清样本各(30例),ELISA检测上述血清SHH的含量.SD大鼠皮内注射2型胶原蛋白(Col2)诱导RA大鼠模型(CIA),取其滑膜组织原代培养滑膜成纤维细胞(SF).免疫荧光细胞化学染色法检测vimentin表达鉴定SF,并检测SHH在SF中的表达.培养SF给予SHH-胶质瘤相关癌基因1(Gli-1)通路特异性阻断剂GANT61处理72 h,Western blot法检测SF表达SHH的变化情况,CCK-8法检测SF的增殖情况.结果 RA患者血清中SHH的含量较SLE、AS患者及正常组含量升高.成功建立CIA模型及分离培养SF;CIA-SF表达SHH较正常组SF高.给予GANT61处理72 h,CIA-SF中SHH蛋白表达降低且细胞增殖水平下降.结论 SHH参与RA发病与CIA-SF增殖有关.

  14. 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

  15. Subtalar joint septic arthritis in a patient with hypogammaglobulinemia.

    Science.gov (United States)

    Wynes, Jacob; Harris, William; Hadfield, Robert A; Malay, D Scot

    2013-01-01

    The clinical presentation of a monoarticular, red, hot, and swollen joint has many possible diagnoses, including septic arthritis, which is 1 of the most devastating. The morbidity associated with this pathologic process involves permanent joint damage and the potential for progression to systemic illness and, even, mortality. The common risk factors for joint sepsis include a history of rheumatoid arthritis, previous joint surgery, joint prosthesis, intravenous drug abuse, alcoholism, diabetes, previous intra-articular steroid use, and cutaneous ulceration. The diagnosis is primarily determined from the culture results after arthrocentesis and correlation with direct visualization, imaging, and various serologies, including synovial analysis. In the present report, a case of an insidious presentation of subtalar joint septic arthritis and its association with a unique patient presentation concomitant with primary immunodeficiency and culture-proven Myocplasma hominis infection is discussed. Septic arthritis has a predilection for the lower extremities and typically is isolated to the hip or knee, with less common involvement of the ankle or metatarsophalangeal joints. Owing to the uncommon nature of primary immunodeficiency disorders and the paucity of studies discussing their association with septic arthridites, we aimed to raise awareness of subtalar joint septic arthritis and to provide a brief overview of the pathogenesis as it presented in a 33-year-old male with X-linked hypogammaglobulinemia/agammaglobulinema.

  16. IMMUNOPATHOGENESIS OF PSORIASIS AND PSORIATIC ARTHRITIS AND PHARMACOLOGICAL PERSPECTIVES

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    A. Genovese

    2011-09-01

    Full Text Available Psoriasis and psoriatic arthritis are chronic inflammatory disorders resulting from a combination of genetic and environmental factors, though the precise causal agents have not yet been identified. The immune system has a major role in their development and the possibility exists that self antigens or antigens from microbial agents, or microbial superantigens initiate a vigorous immune response. Different subsets of T-lymphocytes and dendritic cells, mast cells and granulocytes participate in the pathogenesis and several cytokines and chemokines have been identified in tissue lesions. TNF-α is a key proinflammatory cytokine with important pathogenetic role in psoriasis and psoriatic arthritis. Evidence from clinical trials targeting the TNF-α–TNF-α-receptor supports a central role for this cytokine in the pathogenesis of psoriasis and psoriatic arthritis. Angiogenesis is a prominent early event in lesional psoriatic skin and in synovial membrane psoriatic arthritis. Future potential targets in the treatment of these disorders include biologic agents aimed at blockade of other cytokines, chemokines and angiogenic factors. Key words: Psoriasis, psoriatic arthritis, immunity

  17. PPAR-γ agonist pioglitazone affects rat gouty arthritis by regulating cytokines.

    Science.gov (United States)

    Wang, R-C; Jiang, D-M

    2014-08-28

    The objective was to study peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone regulation effect and its mechanism of expression of cytokines on acute gouty arthritis synovial in rats. Rats with unilateral ankle were injected with artificial monosodium urate (MSU) crystals to make the acute gouty arthritis model. Taking the synovium 48 h after the injection of MSU and using RT-PCR, we assessed the effect of pioglitazone (20 mg·kg(-1)·day(-1), oral administration) on synovial expression, by detecting tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ). The pioglitazone treatment group showed synovial expression of TNF-α, and IFN-γ was significantly lower than in the control group; the inhibition rates were 78.5 and 60.4%. The IL-1 expression difference was not statistically significant between the two groups. Pioglitazone has anti-inflammatory effects on acute gouty arthritis by inhibiting the expression of TNF-α and IFN-γ.

  18. 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.

  19. [Rheumatoid arthritis].

    Science.gov (United States)

    Strunk, J; Lange, U; Müller-Ladner, U

    2005-07-29

    The development of novel anti-rheumatic drugs revolutionizes currently therapeutic strategies and diagnostic management of patients with rheumatoid arthritis, facilitating the goal of true remission instead of only symptomatic treatment as in former years. Since early treatment is known to be crucial for the longterm outcome, imaging modalities such as magnetic resonance imaging and high-frequency ultrasonography including Doppler sonography, which allow direct visualization of very early pathologic alterations of synovitis, or even initial destruction, become increasingly important. Besides the established therapy with methotrexate, new drugs such as leflunomide or the use of various combination therapies have been successfully introduced into the therapeutic armamentarium. Especially the introduction of cytokine-antagonists such as TNF-a inhibitors target the aim of remission. In addition, the upcoming therapeutic agents, which influence very effectively the inflammatory and destructive process need also to be integrated into the concert of different therapeutic strategies in the management of patients with rheumatoid arthritis, which includes the mandatory complementary factors such as physiotherapy, ergotherapy and orthopedic surgery.

  20. 抗环瓜氨酸肽抗体与类风湿关节炎患者成纤维样%Relationship between anti-CCP antibody and migration or invasion ability of fibroblast-like synoviocytes from rheumatoid arthritis patients

    Institute of Scientific and Technical Information of China (English)

    刘志昌; 肖游君; 劳敏曦; 黄明城; 曾珊; 许韩师; 杨岫岩; 梁柳琴

    2013-01-01

    目的:研究抗环瓜氨酸肽(anti-cyclic citrullinated peptide,CCP)抗体与类风湿关节炎(rheumatoid arthritis,RA)患者成纤维样滑膜细胞(fibroblast-like synoviocyte,FLS)迁移和侵袭的关系.方法:FLS分离自22例活动性RA患者、12例骨关节炎(OA)和6例无关节炎病史的外伤患者滑膜组织;FLS迁移和侵袭能力采用Transwell小室测定.结果:RA组、OA组和正常组FLS迁移数目分别为(29.33±10.93)、(9.28±7.87)和(7.00±4.07)个/视野,侵袭细胞数分别为(14.35±7.67)、(3.96±4.37)和(3.08±1.03)个/视野,RA组与其它2组的迁移细胞数和侵袭细胞数比较均有显著差异;抗CCP抗体阳性RA患者FLS与抗CCP阴性RA患者FLS相比,前者迁移和侵袭能力均强于后者;相关性分析亦发现,抗CCP抗体阳性及抗CCP抗体滴度与RA患者FLS的侵袭和迁移能力密切相关.结论:抗CCP抗体阳性的RA患者FLS的迁移和侵袭能力更强,抗CCP抗体可能与RA患者FLS的迁移和侵袭能力改变有关.

  1. Cardiac involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    V. De Gennaro Colonna

    2011-06-01

    Full Text Available Rheumatoid arthritis (RA is a systemic disease of unknown etiology characterized by a chronic inflammatory process mainly leading to destruction of synovial membrane of small and major diarthrodial joints. The prevalence of RA within the general adult population is about 1% and female subjects in fertile age result mostly involved. It’s an invalidating disease, associated with changes in life quality and a reduced life expectancy. Moreover, we can observe an increased mortality rate in this population early after the onset of the disease. The mortality excess can be partially due to infective, gastrointestinal, renal or pulmonary complications and malignancy (mainly lung cancer and non- Hodgkin lymphoma. Among extra-articular complications, cardiovascular (CV involvement represents one of the leading causes of morbidity and mortality. Every cardiac structure can be affected by different pathogenic pathways: heart valves, conduction system, myocardium, endocardium, pericardium and coronary arteries. Consequently, different clinical manifestations can be detected, including: pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of conduction system, coronaropathies and ischemic cardiopathy, valvular disease, pulmonary hypertension and heart failure. Considering that early cardiac involvement negatively affects the prognosis, it is mandatory to identify high CV risk RA patients to better define long-term management of this population.

  2. Effect of Genistein on MAPK Signal Pathway in the Collagen-induced Arthritis Ray Fibroblast-like Synoviocytes%金雀异黄素对胶原诱导性关节炎大鼠成纤维样滑膜细胞MAPK信号通路的影响

    Institute of Scientific and Technical Information of China (English)

    张学增; 张育; 沈维干; 高波; 许金鑫

    2011-01-01

    目的 研究金雀异黄素( genistein,Gen)对类风湿关节炎(rheumatoid arthritis,RA)动物模型胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS) MAPK信号传导通路的影响.方法 建立CIA大鼠模型,将培养的CIA大鼠FLS采用随机法分组,采用四甲基偶氮唑盐(MTT)法检测Gen(浓度分别为50、100、200 μmol/L)对CIA大鼠FLS增殖的影响;采用免疫印迹(Western blot)法检测Gen(浓度分别为50、100、200 μmol/L)对CIA大鼠FLS细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)和磷酸化的细胞外信号调节激酶(phosphorylated extracellular signal-regulated kinase,p-ERK)表达的影响.结果 Gen能够抑制CIA大鼠FLS的增殖,Gen高剂量组细胞增殖度在72h仅为1.10±0.04,明显低于模型组2.12±0.03(P<0.01),并且Gen作用于FLS细胞后,p-ERK表达降低,Gen高剂量组仅为0.34±0.02,明显低于模型组268±0.14(P<0.01),而ERK表达无改变(P>0.05).结论 Gen能够抑制CIA大鼠FLS的增殖,其作用机制主要与下调MAPK信号传导通路的酪氨酸激酶,抑制ERK的磷酸化有关.%Objective To study the effect of genistein (Gen) on MAPK signal pathway in the CIA rat fibro-blast-like synoviocytes (FLS). Methods The rat model of collagen-induced arthritis (CIA) was established. The cultured FLS of CIA rats were divided using randomized method. The effects of Gen (at the concentration of 50, 100, and 200 μmol/L, respectively) on the proliferation of FLS in CIA rats using methyl thiazolyl tetrazolium (MTT) assay. Effects of Gen (at the concentration of 50,100, and 200 μmol/L, respectively) on the expressions of extracellular signal-regulated kinase (ERK) and phosphorylated extracellular signal-regulated kinase (p-ERK) in the FLS of CIA rats were detected. Results Gen could inhibit the proliferation of FLS in CIA rats. The FLS proliferation in the high dose Gen group at 72 h was only 1.10 ± 0

  3. The prevalence of monosodium urate and calcium pyrophosphate crystals in synovial fluid from wrist and finger joints.

    Science.gov (United States)

    Galozzi, Paola; Oliviero, Francesca; Frallonardo, Paola; Favero, Marta; Hoxha, Ariela; Scanu, Anna; Lorenzin, Mariagrazia; Ortolan, Augusta; Punzi, Leonardo; Ramonda, Roberta

    2016-03-01

    The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients' medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP-crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10% in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.

  4. Primary intravascular synovial sarcoma: case report.

    Science.gov (United States)

    Tuncer, Osman Nuri; Erbasan, Ozan; Golbasi, Ilhan

    2012-10-01

    Synovial sarcoma (SS), a mesenchymal spindle cell tumor, displays variable epithelial differentiation, including glandular formation, and features a specific chromosomal translocation, t(X;18)(p11;q11). SS accounts for 5% to 10% of soft-tissue sarcomas. These tumors occur mostly in the joints, especially near the knee, but they also occur in other locations. Primary intravascular SS (IVSS) are extremely rare; only 6 well-documented cases have been reported in the English literature. We describe a new case of primary IVSS of the superior vena cava (SVC) in a 16-year-old boy. A transthoracic echocardiogram confirmed a large (4.8 × 4.6 cm) circumscribed mass filling the right atrium, as well as a moderate pericardial effusion. The mass extended from the SVC to the tricuspid valve but did not prevent valve coaptation. Surgery via a transatrial approach revealed a huge mass (8 to 12 cm) attached to the SVC via a 5-mm pedicle. The tumor was excised, and the patient experienced an uneventful postoperative course. Fluorescence in situ hybridization analysis revealed the presence of the SS-specific translocation.

  5. Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis.

    Science.gov (United States)

    Lundquist, Lisa M; Cole, Sabrina W; Sikes, Martha L

    2014-09-18

    Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs (DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis (RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase (JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type I cytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb's mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaLs (ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.

  6. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

    Directory of Open Access Journals (Sweden)

    Ogrendik M

    2013-05-01

    Full Text Available Mesut OgrendikDivision of Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: A statistically significant association between periodontal disease (PD and systemic diseases has been identified. Rheumatoid arthritis (RA, which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species have been identified as periodontal pathogens, and these organisms are linked to various types of PD. The most analyzed species of periodontopathic bacteria are Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans. Antibodies and DNA from these oral pathogens have been isolated from the sera and synovial fluids of RA patients. This rapid communication describes the role of periodontal pathogens in the etiopathogenesis of RA.Keywords: etiopathogenesis, chronic arthritis, periodontitis, Porphyromonas gingivalis, systemic disease, animal models, antibiotics

  7. Batch correction of microarray data substantially improves the identification of genes differentially expressed in Rheumatoid Arthritis and Osteoarthritis

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    Kupfer Peter

    2012-06-01

    Full Text Available Abstract Background Batch effects due to sample preparation or array variation (type, charge, and/or platform may influence the results of microarray experiments and thus mask and/or confound true biological differences. Of the published approaches for batch correction, the algorithm “Combating Batch Effects When Combining Batches of Gene Expression Microarray Data” (ComBat appears to be most suitable for small sample sizes and multiple batches. Methods Synovial fibroblasts (SFB; purity > 98% were obtained from rheumatoid arthritis (RA and osteoarthritis (OA patients (n = 6 each and stimulated with TNF-α or TGF-β1 for 0, 1, 2, 4, or 12 hours. Gene expression was analyzed using Affymetrix Human Genome U133 Plus 2.0 chips, an alternative chip definition file, and normalization by Robust Multi-Array Analysis (RMA. Data were batch-corrected for different acquiry dates using ComBat and the efficacy of the correction was validated using hierarchical clustering. Results In contrast to the hierarchical clustering dendrogram before batch correction, in which RA and OA patients clustered randomly, batch correction led to a clear separation of RA and OA. Strikingly, this applied not only to the 0 hour time point (i.e., before stimulation with TNF-α/TGF-β1, but also to all time points following stimulation except for the late 12 hour time point. Batch-corrected data then allowed the identification of differentially expressed genes discriminating between RA and OA. Batch correction only marginally modified the original data, as demonstrated by preservation of the main Gene Ontology (GO categories of interest, and by minimally changed mean expression levels (maximal change 4.087% or variances for all genes of interest. Eight genes from the GO category “extracellular matrix structural constituent” (5 different collagens, biglycan, and tubulointerstitial nephritis antigen-like 1 were differentially expressed between RA and OA (RA

  8. Influence of cartilage interstitial fluid on the mRNA levels of matrix proteins, cytokines, metalloproteases and their inhibitors in synovial membrane.

    Science.gov (United States)

    Hyc, Anna; Moskalewski, Stanislaw; Osiecka-Iwan, Anna

    2016-09-01

    Articular cartilage and the synovial membrane both ensure the smooth action of synovial joints; however, the influence of chondrocytes on synovial metabolism remains unclear. The secretory activity of chondrocytes is usually studied in cell cultures and may differ from that in intact cartilage. According to McCutchen's theory of 'weeping' joint lubrication, loading of the articular cartilage during motion squeezes the fluid with lubricating properties from the cartilage. The purpose of the study was to obtain cartilage interstitial fluid (CIF) from intact cartilage and to evaluate its influence on gene expression in the synovial membrane cells. CIF was rinsed out from the cartilage of newborn rats at a pressure of three bar. The chondrocytes survived rinsing and grew in culture. Cytokines in CIF were detected using the enzyme-linked immunosorbent assay (ELISA). The influence of CIF and CIF-like cocktail (all cytokines found in CIF) on gene expression in the synovial membrane cells was studied after a 4 h-incubation, by real-time PCR. Data were analyzed using the Wilcoxon matched-pair test or by the Mann‑Whitney U test. CIF contained basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF)‑1, transforming growth factor β1 (TGFβ1), bone morphogenetic protein 7 (BMP7), macrophage (M)-colony-stimulating factor (CSF), granulocyte (G)-CSF and leukemia inhibitory factor (LIF). CIF stimulated the expression of hyaluronan synthase (HAS)1 and 2, lubricin, collagen I, versican, aggrecan, matrix metalloproteinases (MMPs)2 and 3, tissue inhibitors of metalloproteinases (TIMPs) 1-3, interleukin (IL)-6 and TGFβ1, and decreased the expression of tumor necrosis factor (TNF) and IL-1β. Incubation of the synovial membrane with CIF-like cocktail partially imitated the effects of CIF. Analysis of CIF composition may help to characterize the secretory activity of chondrocytes in their natural environment under various physiological and

  9. Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Directory of Open Access Journals (Sweden)

    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

  11. TGF- induces Lysyl hydroxylase 2b in human synovial osteoarthritic fibroblasts through ALK5 signaling

    NARCIS (Netherlands)

    Remst, Dennis F. G.; Davidson, Esmeralda N. Blaney; Vitters, Elly L.; Bank, Ruud A.; van den Berg, Wim B.; van der Kraan, Peter M.

    2014-01-01

    Lysyl hydroxylase 2b (LH2b) is known to increase pyridinoline cross-links, making collagen less susceptible to enzymatic degradation. Previously, we observed a relationship between LH2b and osteoarthritis-related fibrosis in murine knee joint. For this study, we investigate if transforming growth fa

  12. Arthritis: Frequently Asked Questions

    Science.gov (United States)

    ... of arthritis, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and ankylosing spondylitis. Modifiable risk ... involve the following: Medications. Nonpharmacologic therapies. Physical or occupational therapy. Splints or joint assistive aids. Patient education and ...

  13. Forms of Arthritis

    Science.gov (United States)

    ... this page please turn Javascript on. Forms of Arthritis Past Issues / Fall 2006 Table of Contents Today, ... of Linda Saisselin Osteoarthritis (OA) — the form of arthritis typically occurring during middle or old age, this ...

  14. Rheumatoid arthritis (image)

    Science.gov (United States)

    Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints ... other joints and is worse in the morning. Rheumatoid arthritis is also a systemic disease, involving other body ...

  15. Arthritis in America

    Science.gov (United States)

    ... part of aging. The most common types are osteoarthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia. Arthritis costs ... file ePub file RIS file Page last reviewed: March 7, 2017 Page last updated: March 7, 2017 ...

  16. Sex and Arthritis

    Science.gov (United States)

    ... Call for Letters of Interest Call for Topics Axial Spondyloarthritis Glucocorticoid-Induced Osteoporosis Gout Juvenile Idiopathic Arthritis ... fibromyalgia , scleroderma , osteoarthritis , rheumatoid ... spondylitis , Raynaud’s phenomenon and juvenile arthritis also may experience: ...

  17. Imaging in Psoriatic Arthritis

    DEFF Research Database (Denmark)

    Poggenborg, René Panduro; Østergaard, Mikkel; Terslev, Lene

    2015-01-01

    Psoriatic arthritis (PsA) is an inflammatory joint disease characterized by arthritis and often enthesitis in patients with psoriasis, presenting a wide range of manifestations in various patterns. Imaging procedures are primarily conventional radiography, ultrasonography (US), and magnetic...

  18. Arthritis and the Feet

    Science.gov (United States)

    ... some of the complaints—inflammation, pain, stiffness, excessive warmth, injuries. Even bunions can be manifestations of arthritis. Arthritis may be treated in many ways. Patient education is important. Physical therapy and exercise may be indicated, accompanied by ...

  19. Effect of RICTOR expression on cell viability in rheumatoid arthritis fibroblast-like synoviocytes%RICTOR对类风湿关节炎成纤维样滑膜细胞活力的影响

    Institute of Scientific and Technical Information of China (English)

    郭欣; 胡爱玲; 方霖楷; 刘岩; 潘云峰

    2013-01-01

    目的:通过siRNA介导的RNA干扰技术沉默类风湿关节炎(RA)成纤维样滑膜细胞(FLS)mTORC2的特异组成蛋白RICTOR的表达,观察其对细胞活力的影响.方法:组织块法培养RA-FLS.应用阳离子脂质体转染的方法,把化学合成的特异性RICTOR siRNA转染RA-FLS,并以转染非特异性siRNA作为阴性对照.利用荧光定量PCR法分析转染24h后细胞RICTOR mRNA表达水平的变化;Western blotting法分析转染48和72 h后细胞RICTOR蛋白表达水平的变化;以噻唑蓝(MTr)比色法检测转染成纤维样滑膜细胞不同时间(24、48和72h) RICTOR siRNA对细胞活力的影响.结果:荧光定量PCR结果显示特异性RICTOR siRNA转染组与对照组相比,细胞中RICTOR的mRNA表达水平显著下调,24h干扰效率达78.3%±63.71% (P <0.01).Western blotting结果显示与对照组相比,RICTOR siRNA转染组48 h和72 h后RICTOR蛋白表达水平明显降低,沉默效率分别为92.48%±6.14%和98.57%±1.40%(均P<0.01).MTT结果显示,早期(24和48 h)RICTOR siRNA转染组与阴性对照组细胞存活率比较无显著差异;72 h后,RICTOR siRNA转染组与阴性对照相比,细胞活力明显降低,抑制率为90.14%±1.90% (P<0.01).结论:转染特异性RICTOR siRNA可降低RA-FLS的活力,提示mTORC2可能与RA-FLS的生长有关.%AIM: To investigate the effects of RICTOR expression on the viability of rheumatoid arthritis fibro-blast-like synoviocytes (RA-FLS). METHODS; RA-FLS were obtained by tissue culture. Chemically synthesized double-stranded siRNAs targeting RICTOR gene were transfected info RA-FLS by cationic liposome. The nonspecific siRNA was also transfected into the negative control cells. The mRNA expression of RICTOR was detected by RT-qPCR after transfection for 24 h. Western blotting was used to evaluate the inhibitory effects of siRNAs on RICTOR expression after transfection for 48 h and 72 h. The cell viability was examined by MTT assay. RESULTS; Compared

  20. Intraspinal synovial cysts: A retrospective study

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    Acharya R

    2006-01-01

    Full Text Available Background: We report the clinical presentation, radiographic studies, intraoperative findings, histopathological analysis, and post-treatment outcome in 26 patients diagnosed with spinal synovial cysts (SSCs. Aims: To describe the clinical presentation, radiographic studies, operative findings, and postoperative follow-up in 26 patients with SSCs. Settings and Design: The study was retrospective in design, involving chart review. Individual patient data was tabulated and patterns were recognized. Materials and Methods: The charts for 26 patients who underwent surgical extirpation of SSC between April 1993 and October 2002 were retrospectively reviewed. Specifically, initial clinical presentation, pertinent radiographs (X-rays, magnetic resonance imaging, computed tomography, intraoperative findings, histopathology, and postoperative follow-up were noted. Statistical Analysis Used: Patient data was tabulated and analyzed for patterns in demographics, symptoms and histopathology. Results: SSCs were more common in females than males (17:9 ratio. Presenting symptoms were back pain with radiculopathy in 13 (50%, radicular pain in the absence of back pain in 10 (38%, and back pain without radicular pain in three (11%. In addition, 17 patients (65% had sensory deficit, and 9 (35% had motor deficit. Most SSCs occurred at the lumbar (19/26 or lumbosacral (5/26 regions, with only 2 (2/26 in the thoracic region. One patient had bilateral SSC at the L4-5 level. Intraoperatively, each cyst was located adjacent to a degenerated facet joint. These lesions could grossly be identified intraoperatively and histopathological confirmation was achieved in all the cases. Conclusions: SSCs are important lesions to consider in the differential diagnosis of lumbar epidural masses and surgical resection leads to significant improvement in the majority of cases.

  1. 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

  2. SYNOVIAL SARCOMA IN CHILDHOOD: CLINICAL AND RADIOLOGICAL FINDINGS

    Institute of Scientific and Technical Information of China (English)

    Xu Deyong; Zhan Alai; Luan Hongmei; Feng Weihua; Sun Xihe; Yang Zuwen

    1998-01-01

    Objective: To study the clinical characteristics and radiological features of synovial sarcoma in childhood and its relation to the diagnosis and treatment. Methods:The clinical radiological features of 15 children with synovial sarcoma proved surgically and pathologically were analyzed. Results: In children, the tumor boundaries are poorly defined due to paucity of fat, and metastasis usually occurs early. Eight patients in this series had bone involvement, including: direct erosion by tumor causing cortical destruction, indirect pressure defect with sharp margin and reactive bone sclerosis and bone destruction of the primary intraosseous synovial sarcoma.Conclusion: The tumor is often misdiagnosed, the final confirmed diagnosis must be made by histological examination with imaging findings. It is emphasized that the patients should be treated with radiotherapy and chemotherapy preoperatively and postoperatively.

  3. Synovial fistula after tension band plating for genu valgum correction.

    Science.gov (United States)

    Momaya, Amit; Ray, Peter; Khoury, Joseph

    2015-01-01

    Tension band plating is a commonly performed procedure to address angular deformities about the knee in children. We present a case of a synovial fistula formation after tension band plate removal, an unreported complication in the literature. An 11-year-old girl underwent tension band plating for genu valgum. After removal of the plate, she developed a synovial fistula that was confirmed by magnetic resonance imaging. Her knee was immobilized in extension, which allowed the synovial fistula to heal. The unique capsular anatomy in the knee provides a possible etiology. Physicians performing tension band plating should be aware of this complication and consider a brief period of immobilization of 3 to 5 days after hardware removal to allow the capsular rent to heal.

  4. Simulation Of The Synovial Fluid In A Deformable Cavity

    Science.gov (United States)

    Martinez-Gutierrez, Nancy; Ibarra-Bracamontes, Laura A.

    2016-11-01

    The main components of a synovial joint are a cartilage and a biofluid known as the synovial fluid. The results were obtained using the FLUENT software to simulate the behavior of the synovial fluid within a deformable cavity with a simple geometry. The cartilage is represented as a porous region. By reducing the available region for the fluid, a fluid displacement into the cartilage is induced. The total pressure reached in the interface of the deformable cavity and the porous region is presented. The geometry and properties of the system are scaled to values found in a knee joint. The effect of deformation rate, fluid viscosity and properties of the porous medium on the total pressure reached are analyzed. The higher pressures are reached either for high deformation rate or when the fluid viscosity increases. This study was supported by the Mexican Council of Science and Technology (CONACyT) and by the Scientific Research Coordination of the University of Michoacan in Mexico.

  5. Intra-articular therapy with infliximab in psoriatic arthritis: efficacy and safety in refractory monoarthritis

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    A. Minosi

    2011-06-01

    Full Text Available Objective: To evaluate efficacy and safety of intra-articular therapy (IA with infliximab (IFX, in patients with psoriatic arthritis (PsA and refractory monoarthritis. Methods: Four male and 1 female aged from 25 to 71 years and disease duration from 1 to 25 years, affected by PsA (CASPAR criteria were observed . All patients were treated with immunomodulators (methotrexate, leflunomide, cyclosporin A, 3/5 with concomitant steroids, 4/5 with NSAID’s. Only 1 patient were treated with IFX 5 mg/kg IV every 6 weeks. Before the IFX injection an amount of synovial fluid was aspired from the inflamed site and the anti-TNF injection was echographic guided. Patients were evaluated at regular intervals through clinical and echographic examination and retreated in case of flare. Results: At follow-up visit after 7 days, in all patients treated with the first injection was detected total regression of the inflammation and no new inflamed synovial fluid was observed; power doppler examination shows reduction of local vascularization. Two patients experienced full remission after 6 months and only one injection, 1 patient (arthritis of the wrist was in remission after 2 injections (3 months of interval. In 2 patients with knee arthritis and important synovial hypertrophy good results obtained after the first injection were not maintained afterwards and second injection was ineffective: these patients were evaluated for surgical intervention. Conclusions: Local injections of IFX were safe and well tolerated in all patients. The efficacy in short term was observed in all cases; our supposition is that presence of synovial hypertrophy is cause of worsening.

  6. Advancement in contemporary diagnostic and therapeutic approaches for rheumatoid arthritis.

    Science.gov (United States)

    Kumar, L Dinesh; Karthik, R; Gayathri, N; Sivasudha, T

    2016-04-01

    This review is intended to provide a summary of the pathogenesis, diagnosis and therapies for rheumatoid arthritis. Rheumatoid arthritis (RA) is a common form of inflammatory autoimmune disease with unknown aetiology. Bone degradation, cartilage and synovial destruction are three major pathways of RA pathology. Sentinel cells includes dendritic cells, macrophages and mast cells bound with the auto antigens and initiate the inflammation of the joints. Those cells further activates the immune cells on synovial membrane by releasing inflammatory cytokines Interleukin 1, 6, 17, etc., Diagnosis of this disease is a combinational approach comprises radiological imaging, blood and serology markers assessment. The treatment of RA still remain inadequate due to the lack of knowledge in disease development. Non-steroidal anti-inflammatory drugs, disease modifying anti rheumatic drugs and corticosteroid are the commercial drugs to reduce pain, swelling and suppressing several disease factors. Arthroscopy will be an useful method while severe degradation of joint tissues. Gene therapy is a major advancement in RA. Suppressor gene locus of inflammatory mediators and matrix degrading enzymes were inserted into the affected area to reduce the disease progression. To overcome the issues aroused from those therapies like side effects and expenses, phytocompounds have been investigated and certain compounds are proved for their anti-arthritic potential. Furthermore certain complementary alternative therapies like yoga, acupuncture, massage therapy and tai chi have also been proved for their capability in RA treatment.

  7. Giant rheumatoid synovial cyst of the hip joint: diagnosed by MRI.

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    Patkar D

    1999-10-01

    Full Text Available Synovial cysts are commonly found in the knee joint. Hip Joint is an infrequent site for formation of synovial cysts. The features of a large, synovial cyst on magnetic resonance imaging, occurring in the hip joint, are described.

  8. Primary synovial sarcoma of the abdominal wall: A case report and review of the literature

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    Alsaif H Saif

    2008-01-01

    Full Text Available Synovial sarcoma is a malignant mesenchymal neoplasm which commonly occurs in the extremities of adults, in close association with joint capsules, tendon sheaths, bursae and fascial structures. Only a few cases of synovial sarcoma occurring in the abdominal wall have been reported. A case of a primary synovial sarcoma arising from the anterior abdominal wall fascial aponeurosis is presented.

  9. Psoriatic arthritis treatment: biological response modifiers.

    Science.gov (United States)

    Mease, P J; Antoni, C E

    2005-03-01

    In recent years there has been a surge of interest in the treatment of chronic inflammatory disorders as a result of the development and application of targeted biological therapies. The elucidation of the overlapping cellular and cytokine immunopathology of such diverse conditions as rheumatoid arthritis (RA), Crohn's disease, and psoriasis points to specific targets for bioengineered proteins or small molecules. Similar to clinical trials in RA, trials in psoriatic arthritis (PsA) have shown excellent clinical results with the tumour necrosis factor (TNF) blockers, etanercept, infliximab, and adalimumab in a variety of domains including the joints, quality of life, function, and slowing of disease progress as evidenced radiologically. In addition, these agents have shown benefit in domains more unique to PsA, such as the skin lesions of psoriasis, enthesitis, and dactylitis, pointing out the similar pathogenesis of the disease in the skin, the tendons, and the synovial membrane. This therapy has been generally safe and well tolerated in clinical trials of PsA. Other logical candidates for targeted therapy in development include other anti-TNF agents, costimulatory blockade agents that affect T cell function, blockers of other cytokines such as interleukin (IL)-1, 6, 12, 15, or 18, and B cell modulatory medicines. Also, it will be useful to learn more about the effects of combining traditional disease modifying drugs and the newer biologicals.

  10. Rheumatoid Arthritis and Periodontal Disease. An Update.

    Science.gov (United States)

    Venkataraman, Archana; Almas, Khalid

    2015-01-01

    A review of the epidemiological, pathological and immunological relationships between two chronic inflammatory diseases: rheumatoid arthritis (RA) and periodontal disease (PD). RA is a chronic inflammatory disease of the joints, characterized by loss of connective tissue and mineralized structures, the so-called "synovial membrane." Periodontitis is the inflammatory destruction of the periodontal attachment and alveolar bone. While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are similar. And it is possible that individuals manifesting both PD and RA may suffer from a unifying underlying systemic deregulation of the inflammatory response. There is an overproduction of a variety of cytokines and MMPs that appears to be common in both diseases. Oral health parameters should be more closely monitored in patients with RA, an autoimmune disease. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Interventions to prevent, minimize or treat periodontitis in arthritis patients will definitely promise a better quality of life for these patients.

  11. 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

  12. 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

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    Boesen Mikael

    2011-01-01

    Full Text Available Abstract Background 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 hypertrophy, effusion and hyperemia and US was used for guidance of steroid injection and to assess treatment efficacy. Methods Forty swollen ankles regions were studied in 30 patients (median age 6.5 years, range 1-16 years with JIA. All patients were assessed clinically, by US (synovial hypertrophy, effusion and by color Doppler (synovial hyperemia before and 4 weeks after US-guided steroid injection. Results US detected 121 compartments with active disease (joints, tendon sheaths and 1 ganglion cyst. Multiple compartments were involved in 80% of the ankle regions. The talo-crural joint, posterior subtalar joint, midfoot joints and tendon sheaths were affected in 78%, 65%, 30% and 55% respectively. Fifty active tendon sheaths were detected, and multiple tendons were involved in 12 of the ankles. US-guidance allowed accurate placement of the corticosteroid in all 85 injected compartments, with a low rate of subcutaneous atrophy (4,7%. Normalization or regression of synovial hypertrophy was obtained in 89%, and normalization of synovial hyperemia in 89%. Clinical resolution of active arthritis was noted in 72% of the ankles. Conclusions US enabled exact anatomical location of synovial inflammation in the ankle region of JIA patients. The talo-crural joint was not always involved. Disease was frequently found in compartments difficult to evaluate clinically. US enabled exact guidance of steroid injections, gave a low rate of subcutaneous atrophy and was proved valuable for follow-up examinations. Normalization or regression of synovial hypertrophy and hyperemia was achieved in most cases, which supports the notion that US is an important

  13. Effect of Genistein on the proliferation and apoptosis of fibroblast-like synoviocytes from rats with collagen Ⅱ induced arthritis%金雀异黄素对CIA大鼠成纤维样滑膜细胞增殖、凋亡及其机制的研究

    Institute of Scientific and Technical Information of China (English)

    张育; 张学增; 沈维干; 许金鑫; 马莹莹

    2011-01-01

    Aim To investigate the effects of Genistein Gen ) on the proliferation and apoptosis of fibroblastlike synoviocytes( FLS ) from rats with collagen Ⅱ induced arthritis( CIA ). Methods MTT assay was performed to study the effect of Gen on FLS proliferation.Different concentrations of Cen( 50. 100, 200 μmol ·L-1 )were given to the incubation with FLS and Western blotting assay was used to test the effect of Cen on the expression of bcl-2 .bax,AKT,p-AKT in FLS. Results MTT assay showed that the proliferation of FLS in CIA rats treated with different concentrations of Cen ( 50, 100, 200 μmol · L-1 ) was inhibited significantly ( P < 0. 05 ) in a dose-dependent manner. Western blot analysis showed that different concentrations of Gen increased expression of bax protein in a dose-dependent manner. Meanwhile. the different concentrations of Gen ( 50. 100. 200 μmol · L-1 ) also significantly reduced expression of bcl-2 protein ( P <0. 05 ). The expression of ERK protein in Gen treatment FLS was not significantly different ( P > 0. 05 ).In 72 hour, the expression of p-ERK protein in Gen treatment groups was lower than that in model group ( P < 0. 05 ) in a dose-dependent inhibition with Gen concentrations. Conclusion Gen inhibits the activation of PI3K-AKT signal transduction pathways in FLS of CIA rats. Consequently, Gen may regulate the balance of proliferation and apoptosis in FLS of CIA rats through adjusting signal transduction pathways in FLS.%目的 研究金雀异黄素(Genistein,Gen)对类风湿关节炎(rheumatoid arthritis,RA)动物模型CIA大鼠成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)增殖、凋亡及其PI3K/AKT信号转导通路的影响.方法 采用0、50、100、200 μmol·L-1的Gen处理FLS 24、48、72 h,采用MTT法检测Gen对FLS增殖的影响;免疫印迹(Western blot)法检测Gen对CIA大鼠FLS凋亡蛋白bcl-2、bax表达的影响;Western blot法检测不同浓度的Gen处理后的CIA大鼠FLS

  14. CD147与类风湿关节炎成纤维样滑膜细胞MMPs合成的关系%Enhanced production of MMP-2, MMP-9 by fibroblast cells from rheumatoid arthritis patients when co-cultured with monocytes of high CD147 expression

    Institute of Scientific and Technical Information of China (English)

    吴振彪; 朱平; 卢宁; 史战国; 樊春梅; 王彦宏

    2006-01-01

    目的观察类风湿性关节炎(rheumatoid arthritis, RA)患者成纤维样滑膜细胞(fibroblast-like synoviocytes, FLS)与高表达CD147的单核细胞株(THP-1)共培养后,基质金属蛋白酶(matrix metalloproteinases,MMPs)合成的变化.方法从手术切除的RA患者滑膜组织中,分离FLS,经流式细胞术测定CD14,CD68及免疫组化测定波形纤维蛋白(vimentin)证实后,传代培养.将FLS与高表达 CD147的THP-1共培养,观察THP-1细胞对FLS MMPs合成的影响.用明胶酶谱法测FLS MMP-2,MMP-9含量.同时观察CD147拮抗肽(AP9)对MMPs表达的影响.结果高表达CD147,低表达MMP-2、 MMP-9的THP-1细胞与CD147表达水平低的RA FLS混合培养后,FLS合成MMP-2、 MMP-9水平显著升高,随着THP-1细胞数的增加,MMP-2、 MMP-9的合成量也增加.THP-1对FLS合成MMP-2、 MMP-9的刺激作用可被CD147拮抗肽AP-9所抑制.结论高表达CD147的THP-1细胞对共培养的RA FLS合成MMP-2、MMP-9有刺激作用,这种刺激作用可被CD147拮抗肽AP-9所抑制,提示THP-1表面的CD147对FLS合成MMPs有促进作用.

  15. 辛伐他汀对类风湿关节炎成纤维样滑膜细胞分泌趋化因子的影响及其机制%Inhibitory effect of simvastatin on TNF-α-induced chemokines secretion in rheumatoid arthritis fibroblast like synoviocytes via inhibition of RhoA activation

    Institute of Scientific and Technical Information of China (English)

    陈伟玲; 梁柳琴; 邱茜; 叶玉津; 詹钟平

    2011-01-01

    目的:研究降脂药辛伐他汀(SMV)对类风湿关节炎(RA)成纤维样滑膜细胞(FLS)分泌趋化因子的影响及其机制研究.方法:FLS分离自活动性RA患者滑膜组织;小分子GTP酶RhoA活性检测采用pull-down 方法;趋化因子水平采用ELISA检测;细胞活性检测采用MTT法.结果:辛伐他汀(1 μmol/L)显著抑制肿瘤坏死因子α(TNF-α)诱导的白细胞介素-8(IL-8)和单核细胞趋化蛋白(MCP-1)分泌,对RhoA活化也有显著的抑制作用;辛伐他汀的上述抑制作用可被甲羟戊酸(MEVA)和焦磷酸香叶基香叶酯(GGPP)逆转.RhoA抑制剂C3转移酶对TNF-α诱导的IL-8、MCP-1等趋化因子分泌亦有显著的抑制作用.结论:辛伐他汀通过调节RhoA活性对TNF-α诱导的趋化因子分泌发挥抑制作用,提示抑制趋化因子分泌可能是辛伐他汀有效治疗RA的机制之一.%AIM: To investigate the effect of simvastatin ( SMV ) on tumor necrosis factor a ( TNF - a ) - induced chemokine secretion in rheumatoid arthritis fibroblast - like synoviocytes ( RA FLS ). METHODS: RhoA activity was determined by pull - down assay. Chemokine secretion was measured by ELISA. MTT test was used to detect cell viability. RESULTS: Simvastatin attenuated TNF - a - induced interleukin - 8( IL - 8 ) and monocyte chemotactic protein - 1 ( MCP - 1 ) secretion as well as RhoA activation in RA FLS. The inhibitory effects of SMV were completely reversed by me-valonate ( MEVA ) and geranylgeranyl pyrophosphate ( GGPP ). Suppression of RhoA activation with a specific inhibitor depressed the secretion of IL - 8 and MCP - 1 in TNF - a - induced RA FLS. CONCLUSION: Simvastatin inhibits TNF - a - induced secretion of IL - 8 and MCP - 1 in RA FLS through inhibition of RhoA activation, indicating a novel strategy for anti - inflammatory effects of statins on treatment of RA.

  16. Quantification of joint inflammation in rheumatoid arthritis by time-resolved diffuse optical spectroscopy and tracer kinetic modeling

    Science.gov (United States)

    Ioussoufovitch, Seva; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith; Diop, Mamadou

    2015-03-01

    Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation, which can cause progressive joint damage and disability. Diffuse optical spectroscopy (DOS) and imaging have the potential to become potent monitoring tools for RA. We devised a method that combined time-resolved DOS and tracer kinetics modeling to rapidly and reliably quantify blood flow in the joint. Preliminary results obtained from two animals show that the technique can detect joint inflammation as early as 5 days after onset.

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

    Science.gov (United States)

    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.

  18. 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.

  19. Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning

    Science.gov (United States)

    Badillo-Soto, Martha Adriana; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Daza-Benitez, Leonel; Bollain-y-Goytia, Juan José; Carrillo-Jiménez, Miguel Angel; Avalos-Díaz, Esperanza; Herrera-Esparza, Rafael

    2016-01-01

    Objective The molecular mechanism of citrullination involves the calcium-dependent peptidylarginine deiminase (PAD) family of enzymes. These enzymes induce a stereochemical modification of normal proteins and transform them into autoantigens, which in rheumatoid arthritis trigger a complex cascade of joint inflammatory events followed by chronic synovitis, pannus formation, and finally, cartilage destruction. By hypothesizing that PAD2 and PAD4 enzymes produce autoantigens, we investigated five possible synovial protein targets of PAD enzymes. Material and Methods We measured PAD2, PAD4, and citrullinated proteins in 10 rheumatoid and 10 osteoarthritis synovial biopsies and then assessed the post-translational modifications of fibrinogen, cytokeratin, tubulin, IgG, and vimentin proteins using a double-fluorescence assay with specific antibodies and an affinity-purified anti-citrullinated peptide (CCP) antibody. The degree of co-localization was analyzed, and statistical significance was determined by ANOVA, Fisher’s exact test, and regression analysis. Results The principal results of this study demonstrated that citrullinated proteins, such as fibrinogen, IgG, and other probed proteins, were targets of PAD2 and PAD4 activity in rheumatoid synovial biopsies, whereas osteoarthritis biopsies were negative for this enzyme (p<0.0001). An analysis of citrullination sites using the UniProtKB/Swiss-Prot data bank predicts that the secondary structure of the analyzed proteins displays most of the sites for citrullination; a discussion regarding its possible meaning in terms of pathogenesis is made. Conclusion Our results support the conclusion that the synovial citrullination of proteins is PAD2 and PAD4 dependent. Furthermore, there is a collection of candidate proteins that can be citrullinated. PMID:27708970

  20. Isorhamnetin attenuates collagen-induced arthritis via modulating cytokines and oxidative stress in mice

    OpenAIRE

    Wang, Xuewen; Zhong, Wei

    2015-01-01

    Inflammation and oxidative stress were involved in the development and progression of rheumatoid arthritis (RA). Isorhamnetin has anti-inflammatory and anti-oxidative activities, but its effects on RA have not been investigated. In order to observe the possible therapeutic effects of isorhamnetin on RA, we established a collagen-induced arthritis mouse model and treated the animal with isorhamnetin for 3 weeks. Besides, fibroblast-like synoviocytes (FLS) were treated with lipopolysaccharide (...

  1. Infection and immune-mediated meningococcal-associated arthritis: combination features in the same patient

    Directory of Open Access Journals (Sweden)

    Karim Yaqub Ibrahim

    2012-04-01

    Full Text Available We present a case of a 16-year-old male patient with sudden-onset, rash, arthritis and meningitis by Neisseria meningitidis one week after an acute upper respiratory infection. On the 10th day of treatment followed by neurological and arthritis clinical improvement, he presented once again a tender and swollen left knee with a moderate effusion, and active and passive range of motion was severely limited secondary to pain, and when he was submitted to surgical drainage and synovial fluid analysis he showed inflammatory characteristics. A non-steroidal anti-inflammatory drug was taken for five days with complete improvement of symptoms. The case is notable for its combination of features of septic and immune-mediated arthritis, which has rarely been reported in the same patient.

  2. Synovial sarcoma. An immunohistochemical study of the epithelial component

    DEFF Research Database (Denmark)

    Jørgensen, L J; Lyon, H; Myhre-Jensen, O;

    1994-01-01

    Twenty-five synovial sarcomas were studied with a battery of antibodies directed against keratin and epithelial membrane antigen (EMA). The keratin antibody MNF 116 showed reactivity in 24 tumors. In addition, 22 tumors showed reactivity with the antibody Keratin Wide Spectrum, 20 with the antibody...

  3. Synovial hypertrophy causing recurrent hemarthrosis after total knee replacement.

    Science.gov (United States)

    Gajjar, Shreyash M; Platts, Andrew; Dowd, George

    2010-03-01

    Recurrent hemarthrosis following total knee replacement is relatively uncommon and can result from causes that may not always be easy to diagnose. We report three patients with late-onset recurrent hemarthrosis following total knee replacement due to synovial hypertrophy and impingement, which were successfully treated by embolization.

  4. Development of a Synthetic Synovial Fluid for Tribological Testing

    Directory of Open Access Journals (Sweden)

    Emely Lea Bortel

    2015-12-01

    Full Text Available Wear tests of joint prostheses are usually performed using bovine calf serum. The results from different laboratories are hardly ever comparable as, for example, the protein concentration and the protein composition of the serum-based test liquids vary. In addition, the viscosity of these test liquids is similar to that of water and does not match the more viscous synovial fluid. The present work was aimed at developing a synthetic synovial fluid as an alternative to the existing test liquids. Improved consistency and reproducibility of results at a similar price were required. Hyaluronic acid (HA, the lyophilized proteins bovine serum albumin (BSA and immunoglobulin G (IgG, the phospholipid lecithin (PL and salts were applied in a stepwise approach to replace the actually used test liquid based on newborn calf serum. The in vitro results obtained with ultra-high-molecular-weight polyethylene (UHMWPE pins sliding against CoCrMo discs revealed that the developed synthetic synovial fluid fulfils the set requirements: increase of viscosity, reasonable cost, improved consistency and wear particles which resemble the ones found in vivo. The developed synthetic synovial fluid with 3 g/L HA, 19 g/L BSA, 11 g/L IgG, 0.1 g/L PL and Ringer solution is a more realistic alternative to the used serum-based test liquid.

  5. The (epi)genetics of human synovial sarcoma

    NARCIS (Netherlands)

    de Bruijn, Diederik R. H.; Nap, Jan-Peter; van Kessel, Ad Geurts

    2007-01-01

    Human synovial sarcomas are aggressive soft tissue tumors with relatively high rates of recurrences and metastases. They display a variable response to common treatment protocols such as radiation and chemotherapy. For the development of novel diagnostic, prognostic, and therapeutic approaches, deta

  6. The (epi)genetics of human synovial sarcoma.

    NARCIS (Netherlands)

    Bruijn, D.R.H. de; Nap, J.P.; Geurts van Kessel, A.H.M.

    2007-01-01

    Human synovial sarcomas are aggressive soft tissue tumors with relatively high rates of recurrences and metastases. They display a variable response to common treatment protocols such as radiation and chemotherapy. For the development of novel diagnostic, prognostic, and therapeutic approaches, deta

  7. Automated counting of white blood cells in synovial fluid.

    NARCIS (Netherlands)

    R. de Jonge (Robert); R.W. Brouwer (Reinoud); M. Smit (Marij); M. de Frankrijker-Merkestijn; R.J. Dolhain; J.M.W. Hazes (Mieke); A.W. van Toorenenbergen (Albert); J. Lindemans (Jan)

    2004-01-01

    textabstractOBJECTIVES: To evaluate the performance of automated leucocyte (white blood cell; WBC) counting by comparison with manual counting. METHODS: The number of WBC was determined in heparinized synovial fluid samples by the use of (i) a standard urine cytometer (Kova) and a

  8. Synovial cysts of the lumbar spine: a review.

    Science.gov (United States)

    Radatz, M; Jakubowski, J; Cooper, J; Powell, T

    1997-12-01

    Four cases of synovial cyst (ganglion) arising from the facet joints of the lumbar spine are reported. A typical presenting feature was exacerbation of pain on standing or walking, mimicking vascular claudication. MRI proved in all four cases to be the definitive investigation and surgery the treatment of choice, producing excellent results.

  9. Increasing feasibility and patient comfort of MRI in children with juvenile idiopathic arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Hemke, Robert [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands); Emma Children' s Hospital AMC, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Amsterdam (Netherlands); Veenendaal, Mira van; Kuijpers, Taco W. [Emma Children' s Hospital AMC, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Amsterdam (Netherlands); Rossum, Marion A.J. van [Emma Children' s Hospital AMC, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Amsterdam (Netherlands); Jan van Breemen Institute, Department of Pediatric Rheumatology, Amsterdam (Netherlands); Maas, Mario [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands)

    2012-04-15

    MRI is the most sensitive imaging modality in juvenile idiopathic arthritis (JIA), but has practical limitations. Optimizing the scanning protocol is, therefore, necessary to increase feasibility and patient comfort. To determine the feasibility of bilateral non-contrast-enhanced open-bore MRI of knees and to assess the presence of literature-based MRI features in unsedated children with JIA. Children were classified into two clinical subgroups: active arthritis (group 1; n = 29) and inactive disease (group 2; n = 18). MRI features were evaluated using a literature-based score, comprising synovial hypertrophy, cartilage lesions, bone erosions, bone marrow changes, infrapatellar fat pad heterogeneity, effusion, tendinopathy and popliteal lymphadenopathy. The MRI examination was successfully completed in all 47 children. No scan was excluded due to poor image quality. Synovial hypertrophy was more frequent in group 1 (36.2%), but was also seen in 19.4% of the knees in group 2. Infrapatellar fat pad heterogeneity was more prevalent in group 2 (86.1%; P = 0.008). Reproducibility of the score was good (Cohen kappa, 0.49-0.96). Bilateral non-contrast-enhanced open-bore knee MRI is feasible in the assessment of disease activity in unsedated children with JIA. Signs differing among children with active and inactive disease include infrapatellar fat pad heterogeneity and synovial hypertrophy. (orig.)

  10. Septic arthritis: what is the role for the rheumatologist?

    Directory of Open Access Journals (Sweden)

    V. Carraro

    2011-09-01

    Full Text Available Septic arthritis (SA is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible loss of function. The reported incidence varies from 2-5 cases per 100.000 individuals per year in the general populations to 70 cases per 100.000 individuals annually among patients with rheumatoid arthritis (RA. Predisposing factors are immunosuppressive and corticosteroids therapy and RA “itself”. The expected decrease in incidence of SA was not seen over the last 20 years period but we can, on the contrary, expect an increase in the frequency of its appearance because of the population ageing, the increasingly prosthetic joint replacement, the ability of the bacteria to evade clearance by the host immune response and the rapidly growing number of patients with RA, ankylosing spondylitis and psoriatic arthritis treated with tumour necrosis factor α (TNFα antagonists. Up to now there have been conflicting reports regarding joint infections in patients under anti-TNF therapy but according to data from Deutsch as well as the British register there might be an increase in the incidence of joint infections in anti TNF treated patients. Microscopic analysis and culture of synovial fluid are fundamental diagnostic tools in the evaluation of possible joint sepsis. Sonographic guidance of arthrocentesis led to successful aspiration of difficultto- access joints as shoulder and hip. There is controversy over which mode of drainage of septic synovial fluid should be employed but needle aspiration appear to be preferable to surgical treatment as an initial mode of treatment of SA. Rheumatologists should have a central role in the diagnosis and management of SA.

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

    Directory of Open Access Journals (Sweden)

    Renoud J Marijnissen

    Full Text Available BACKGROUND: 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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. CONCLUSION: 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.

  12. How undifferentiated arthritis evolves into chronic arthritis.

    Science.gov (United States)

    van der Woude, D; Toes, R E M; Scherer, H U

    2014-08-01

    Undifferentiated arthritis (UA) is a frequently occurring clinical presentation with a variable outcome. While some forms of UA will spontaneously remit, other forms will progress to chronic arthritis; an outcome that would preferably be prevented. Which immunological factors are normally at the basis of resolution of inflammation, and what, on the other hand, causes inflammation to persist? This review provides an overview of the immunological mechanisms involved in these two scenarios, including specific examples of how these mechanisms apply, or can be influenced in rheumatic diseases. Furthermore, what do we know about risk factors for chronic arthritis, such as the development of autoantibodies? The recent years have provided many insights concerning risk factors for autoantibody-positive versus autoantibody-negative rheumatoid arthritis, which are discussed along with a possible pathophysiological model incorporating autoantibodies into the larger process of disease development. Finally, the evolution of the autoantibody response over time is described.

  13. TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to tumour necrosis factor blockade

    NARCIS (Netherlands)

    A.W.R. van Kuijk; C.A. Wijbrandts; M. Vinkenoog; T.S. Zheng; K.A. Reedquist; P.P. Tak

    2010-01-01

    Objective: To investigate the expression of tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) in the inflamed synovium of patients with arthritis, as TWEAK blockade has been observed to have a beneficial effect in an ani

  14. Dynamic contrast-enhanced magnetic resonance imaging of the wrist in early arthritis

    Directory of Open Access Journals (Sweden)

    M.A. Cimmino

    2011-09-01

    Full Text Available Objectives: MRI has been proposed as the imaging method of choice to evaluate the long-term outcome in patients with early arthritis. The role of dynamic MRI, performed at presentation, in predicting the outcome of patients with early arthritis has been addressed in the present study. Methods: 39 patients with early arthritis, involving at least one wrist, were studied with clinical visits and laboratory investigations, every 3 months. Dynamic MRI was performed with a low-field (0.2T, extremity-dedicated machine (Artoscan, Esaote, Genova, Italy equipped with a permanent magnet and with a dedicated hand and wrist coil. During the intravenous injection of Gd-DTPA, twenty consecutive fast images of 3 slices of the wrist were acquired. The synovial contrast enhancement ratio was calculated both as rate of early enhancement (REE per second during the first 55” and as relative enhancement (RE at t seconds. Results: In our cohort of patients, REE and RE were significantly lower than those observed in a historical cohort of 36 patients with active rheumatoid arthritis. In univariate analysis, low RE predicted complete remission of arthritis. In multivariate analysis, fulfillment of RA criteria during follow-up was predicted by high RE. The need for immunosuppressive treatment at the end of follow-up was predicted by both low RE and high REE. Conclusions: Dynamic MRI may be used to predict several outcomes of early arthritis involving the wrist

  15. Infections and arthritis.

    Science.gov (United States)

    Mathew, Ashish Jacob; Ravindran, Vinod

    2014-12-01

    Bacteria, viruses, fungi, and parasites can all cause arthritis of either acute or chronic nature, which can be divided into infective/septic, reactive, or inflammatory. Considerable advances have occurred in diagnostic techniques in the recent decades resulting in better treatment outcomes in patients with infective arthritis. Detection of emerging arthritogenic viruses has changed the epidemiology of infection-related arthritis. The role of viruses in the pathogenesis of chronic inflammatory arthritides such as rheumatoid arthritis is increasingly being recognized. We discuss the various causative agents of infective arthritis and emphasize on the approach to each type of arthritis, highlighting the diagnostic tests, along with their statistical accuracy. Various investigations including newer methods such as nucleic acid amplification using polymerase chain reaction are discussed along with the pitfalls in interpreting the tests.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Small ruminant lentivirus-induced arthritis: clinicopathologic findings in sheep infected by a highly replicative SRLV B2 genotype.

    Science.gov (United States)

    Pérez, M; Biescas, E; Reina, R; Glaria, I; Marín, B; Marquina, A; Salazar, E; Álvarez, N; de Andrés, D; Fantova, E; Badiola, J J; Amorena, B; Luján, L

    2015-01-01

    We describe the clinicopathologic features of an arthritis outbreak in sheep induced by small ruminant lentivirus (SRLV), linked to the presence of a new SRLV isolate phylogenetically assigned to caprine arthritis encephalitis virus-like subgroup B2. Thirteen SRLV seropositive Rasa Aragonesa adult ewes were selected from 5 SRLV highly infected flocks (mean serop