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Sample records for arthritis fibroblast-like synoviocytes

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

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    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.

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

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    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

  3. Increased autophagy in fibroblast-like synoviocytes leads to immune enhancement potential in rheumatoid arthritis.

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    Yang, Ru; Zhang, Yingzi; Wang, Lin; Hu, Ji; Wen, Jian; Xue, Leixi; Tang, Mei; Liu, Zhichun; Fu, Jinxiang

    2017-02-28

    The incidence of rheumatoid arthritis (RA) has been reported to be correlated with a disorder of immunregulation. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play an important role in regulating the local immune microenvironment. However, the potential mechanism of RA-FLS in regulating the immnue response is not clearly understood. In this study, we demonstrated that the expression of HIF-1α was significantly up-regulated in rheumatoid arthritis tissue which indicated that the hypoxia condition in the microenvironment. We also observed that RA-FLSs demonstrated the potential to up-regulate immune activation. Meanwhile, the level of autophagy increased in RA-FLSs compared with control group. Besides that, the expression of IL-6 was up-regulated not only in RA-FLSs but also in the fibroblasts that treated with hypoxia condition. Accordingly, we found that autophagy inhibitiors could effectively inhibit the immune activation function of RA-FLSs medicated by IL-6. Taken together, the results we demonstrated above indicated that the hypoxia microenvironment could effectively induce the incidence of autophagy and then lead to the immune activation function of RA-FLSs medicated by IL-6.

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

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    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

  5. Anti-Inflammatory Effects of TRAF-Interacting Protein in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

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    Qing-Zhu Kong

    2016-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA- FLS. Overexpression of TRIP significantly inhibited the activation of NF-κB signaling and decreased the production of proinflammatory cytokines and matrix metalloproteinases (MMPs in TNFα-stimulated RA-FLS. Furthermore, TRIP was found to interact with transforming growth factor β-activated kinase 1 (TAK1 and promoting K48-linked polyubiquitination of TAK1 in RA-FLS. Our results demonstrate that TRIP has anti-inflammatory effects on RA-FLS and suggest TRIP as a potential therapeutic target for human RA.

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

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

    2015-08-01

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

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

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    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

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

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    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.

  9. Interleukin-35 upregulates OPG and inhibits RANKL in mice with collagen-induced arthritis and fibroblast-like synoviocytes.

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    Li, Y; Li, D; Li, Y; Wu, S; Jiang, S; Lin, T; Xia, L; Shen, H; Lu, J

    2016-04-01

    IL-35 is a novel anti-inflammatory cytokine, but the exact role of IL-35 in the progression of RA remains unclear, especially associated with osteoporosis and bone erosion. The present research has not been reported. Our purpose is to study how IL-35 affects RA bone destruction. This study investigated the effect of interleukin-35 (IL-35) on OPG and RANKL expression in collagen-induced arthritis (CIA) in rats and in cultured fibroblast-like synoviocytes (FLS). Thirty DBA/1J mice were randomly assigned to three groups (n = 10 per group): the control group, the CIA group, and the CIA + IL-35 group. Collagen-induced arthritis was induced by immunization with collagen. IL-35 was intraperitoneally injected daily for 10 days, starting from the 24(th) day after immunization. FLS cells were isolated and cultured from CIA. The expression of IL-17, RANKL, and OPG was determined by RT-PCR and Western blot. Each experiment was repeated three times. CIA mice exhibited arthritis symptoms on day 24, followed by a rapid progression of arthritis. The expression of IL-17 and RANKL was increased and the expression of OPG was decreased in CIA mice compared with control mice. IL-35 treatment inhibited the development of arthritis in CIA mice, accompanied by a decrease in the expression of IL-17 and RANKL and an increase in the expression of OPG. Furthermore, IL-35 dose-dependently inhibited the expression of RANKL and increased the expression of OPG in cultured FLS cells. IL-35 inhibits RANKL expression and increases OPG expression in CIA mice. IL-35 may be used for treating rheumatoid arthritis.

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

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    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.

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

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    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.

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

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    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

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

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    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.

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

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    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.

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

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

    2012-06-01

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

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

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    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.

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

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    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.

  18. Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-like synoviocytes in rheumatoid arthritis.

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    Chen, Dongying; Zeng, Shan; Huang, Mingcheng; Xu, Hanshi; Liang, Liuqin; Yang, Xiuyan

    2017-04-01

    To probe the role of protein arginine methyltransferase 5 (PRMT5) in regulating inflammation, cell proliferation, migration and invasion of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). FLSs were separated from synovial tissues (STs) from patients with RA and osteoarthritis (OA). An inhibitor of PRMT5 (EPZ015666) and short interference RNA (siRNA) against PRMT5 were used to inhibit PRMT5 expression. The standard of protein was measured by Western blot or immunofluorescence. The excretion and genetic expression of inflammatory factors were, respectively, estimated by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Migration and invasion in vitro were detected by Boyden chamber assay. FLSs proliferation was detected by BrdU incorporation. Increased PRMT5 was discovered in STs and FLSs from patients with RA. In RA FLSs, the level of PRMT5 was up-regulated by stimulation with IL-1β and TNF-α. Inhibition of PRMT5 by EPZ015666 and siRNA-mediated knockdown reduced IL-6 and IL-8 production, and proliferation of RA FLSs. In addition, inhibition of PRMT5 decreased in vitro migration and invasion of RA FLSs. Furthermore, EPZ015666 restrained the phosphorylation of IκB kinaseβ and IκBα, as well as nucleus transsituation of p65 as well as AKT in FLSs. PRMT5 regulated the production of inflammatory factors, cell proliferation, migration and invasion of RA FLS, which was mediated by the NF-κB and AKT pathways. Our data suggested that targeting PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  19. 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.

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    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.

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

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    Nishioku Tsuyoshi

    2012-11-01

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

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

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    Jyh-Horng Wang

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

  2. 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.

  3. 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.

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

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    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.

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

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    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.

  6. 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.

  7. 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.

  8. 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.

    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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

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

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    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.

  14. Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

    Science.gov (United States)

    Tang, Qin; Cui, Jianyu; Tian, Zhonghua; Sun, Jiangchuan; Wang, Zhigang; Chang, Shufang; Zhu, Shenyin

    2017-01-01

    Background Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide-co-glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP–mediated PSDT on MH7A synoviocytes. Methods The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP–mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation. Results The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP–mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP–mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N-acetylcysteine. Conclusion Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP–mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase

  15. 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

  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

  17. 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

  18. The effects of levofloxacin on rabbit fibroblast-like synoviocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yang; Lu, Kaihang; Deng, Yu; Cao, Hong; Chen, Biao [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)

    2012-12-01

    It is widely accepted that tendon and cartilage are adversely affected with the toxic effects of quinolones. However, the effects of quinolones on synovium have not been deciphered completely. In this study, our main objective was to investigate the effects of levofloxacin, a typical quinolone antibiotic drug, on fibroblast-like synoviocytes (FLSs) in vitro. FLSs of rabbits were treated with levofloxacin at different concentrations (0, 14, 28, 56, 112 and 224 μM). The possible cytotoxic effects of levofloxacin on FLS were determined. Levofloxacin significantly reduced the cell viabilities, gene expression of hyaluronan synthase-2 (HAS-2), and the level of hyaluronan in FLSs. Moreover, levofloxacin-induced concentration-dependent increases of apoptosis and active caspase-3 were determined in this study. Ultrastructural damages of FLSs were observed by electron microscopy. The mRNA expression levels of matrix metalloproteinase (MMP)-3 and MMP-13 were increased in FLSs treated with levofloxacin. In addition, levofloxacin played a role in suppressing the expression of interleukin (IL)-1 and IL-6. Our data suggest that the cytotoxic effects of levofloxacin on FLS were shown to be able to affect cell viability and HA synthesis capacity. The potential mechanisms of the cytotoxic effects may be attributed to the apoptosis and increased expression of MMPs. -- Highlights: ► Levofloxacin decreases hyaluronic acid synthesis in fibroblast-like synoviocytes. ► Levofloxacin exerts pro-apoptosis effects on fibroblast-like synoviocytes. ► Levofloxacin increases gene expression of MMPs in fibroblast-like synoviocytes. ► Levofloxacin exerts anti-inflammatory effects on fibroblast-like synoviocytes.

  19. Effect of 1,25-(OH2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ping Fan

    2017-05-01

    Full Text Available Objective: This study aims to investigate the regulatory mechanism of 1,25-(OH2D3 on the proliferation of fibroblast-like synoviocytes (FLS and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA rats via microRNA-22 (miR-22. Methods: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1β, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR. Results: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and PGE2, and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH2D3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH2D3 + miR-22 mimics group. Conclusion: Our study demonstrated that 1,25-(OH2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.

  20. Brazilin Limits Inflammatory Responses through Induction of Prosurvival Autophagy in Rheumatoid Fibroblast-Like Synoviocytes.

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    Hyunji Lee

    Full Text Available Brazilin is an active compound of Caesalpinia sappan L. (Leguminosae, which possesses pro-apoptotic and anti-inflammation potentials depending on the specific cell type. However, it is largely unknown whether autophagy is implicated in the mechanism underlying its chemotherapeutic and anti-inflammatory effects in rheumatoid arthritis (RA. Here, we show that treatment of RA fibroblast-like synoviocytes (FLS with brazilin results in enhanced level of autophagic flux, evidenced by accumulation of autophagosome and increased level of lipidated LC3 (LC3-II, which is mainly mediated by enhanced production of reactive oxygen species (ROS. Interestingly, long-term exposure of brazilin was able to restore cell survival against the cytotoxity, exclusively in RA FLS, but not in normal fibroblast. Importantly, such a restoration from brazilin-induced cytotoxity in RA FLS was completely abrogated after co-treatment with autophagy inhibitors including NH4Cl or chloroquine. Furthermore, we found that the pretreatment of RA FLS with brazilin reduced LPS- or TNF-induced NF-κB activation and the secretion of inflammatory cytokines in parallel with the enhanced autophagic flux. Such anti-NF-κB potentials of brazilin were drastically masked in RA FLS when autophagy was suppressed. These results suggest that brazilin is capable of activating autophagy exclusively in RA FLS, and such inducible autophagy promotes cell survival and limits inflammatory response.

  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. Eicosapentaenoic Acid Suppresses the Proliferation of Synoviocytes from Rheumatoid Arthritis

    Science.gov (United States)

    Hamaguchi, Masahide; Kawahito, Yutaka; Omoto, Atsushi; Tsubouchi, Yasunori; Kohno, Masataka; Seno, Takahiro; Kadoya, Masatoshi; Yamamoto, Aihiro; Ishino, Hidetaka; Matsuyama, Masahide; Yoshimura, Rikio; Yoshikawa, Toshikazu

    2008-01-01

    Eicosapentaenoic acid (EPA) is essential for normal cell growth, and may play an important role in inflammatory and autoimmune disorders including rheumatoid arthritis. We investigate that EPA could suppress the proliferation of fibroblast like synoviocytes in vitro. We treated synoviocytes with 1 to 50 µM EPA and measured cell viabilities by the modified MTT assay. We sorted the number of them in sub G1 stage by fluorescence-activated cell sorting caliber. And we stained them by light green or Hoechst 33258, and investigate microscopic appearance. The cell viabilities were decreased at 30 µM, 40 µM, and 50 µM of EPA comparing to 0 µM of EPA. The half maximal concentration of synoviocytes inhibition was approximately 25 µM. At day 1 and day 3, cell number was also decreased at 50 µM EPA comparing to control. FACS caliber indicated the number of synoviocytes in sub G1 stage did not increase in each concentration of EPA. Hoechst staining indicated normal chromatin pattern and no change in a nuclear morphology both in EPA treated synoviocytes and in untreated synoviocytes. These findings suggest that EPA could suppress the proliferation of synoviocytes in vivo dose dependently and time dependently, however, the mechanism is not due to apoptosis. PMID:18818751

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

    Directory of Open Access Journals (Sweden)

    Bing Wang

    2017-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction. Activation of fibroblast-like synoviocytes (FLS is a critical step that promotes disease progression. In this study, we aimed to explore the effect of interleukin-34 (IL-34 on RA FLS as a proinflammatory factor and IL-34-stimulated FLS on the production of Th17. We found that serum IL-34 levels were increased compared to those of the healthy controls and had positive correlations with C-reactive protein (CRP, erythrocyte sedimentation rate (ESR, rheumatoid factor (RF, and anticyclic citrullinated peptide (CCP antibody accordingly. CSF-1R was also highly expressed on RA FLS. The interaction of IL-34 and CSF-1R promoted a dramatic production of IL-6 by FLS through JNK/P38/NF-κB signaling pathway. Further, the IL-34-stimulated IL-6 secretion by RA FLS was found to upregulate the number of Th17. The treatment of IL-6R antagonist could attenuate the production of Th17 mediated by IL-34-stimulated RA FLS. Our results suggest that the increased IL-34 levels were closely related to the disease activity of RA. Additionally, the overexpression of IL-6 in the IL-34-stimulated FLS promoted the generation of Th17. Therefore, IL-34 was supposed to be involved in the pathogenesis of RA. The inhibition of IL-34 might provide a novel target for therapies of RA.

  4. Inhibition of TNF-{alpha}-mediated inflammatory responses by a benzodioxolylacetylamino-linked benzothiazole analog in human fibroblast-like synoviocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young-Rae [Department of Biochemistry, Research Institute for Endocrine Sciences and Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guo Hua [College of Pharmacy, Sookmyung Women' s University, 52 Hyochangwon-gil, Yongsan-gu, Seoul 140-742 (Korea, Republic of); Lee, Sang-Myeong [Division of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan, Jeonbuk 570-752 (Korea, Republic of); Park, Jin-Woo [Department of Biochemistry, Research Institute for Endocrine Sciences and Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Ryu, Jae-Ha [College of Pharmacy, Sookmyung Women' s University, 52 Hyochangwon-gil, Yongsan-gu, Seoul 140-742 (Korea, Republic of); Jeon, Raok, E-mail: rjeon@sm.ac.kr [College of Pharmacy, Sookmyung Women' s University, 52 Hyochangwon-gil, Yongsan-gu, Seoul 140-742 (Korea, Republic of); Park, Byung-Hyun, E-mail: bhpark@jbnu.ac.kr [Department of Biochemistry, Research Institute for Endocrine Sciences and Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

    2011-05-20

    Highlights: {yields} We synthesized SPA0537, a benzothiazole analog. {yields} SPA0537 is a potent NF-{kappa}B inhibitor. {yields} SPA0537 suppresses the production of proinflammatory mediators in human rheumatoid fibroblast-like synoviocytes. {yields} SPA0537 is effective at suppressing osteoclast differentiation. -- Abstract: The pathologic processes of rheumatoid arthritis are mediated by a number of cytokines, chemokines, and matrix metalloproteinases, the expressions of which are controlled by NF-{kappa}B. This study was performed to explore the effects of a benzothiazole analog, SPA0537, on the control of the NF-{kappa}B activation pathway. We also investigated whether SPA0537 had any anti-inflammatory effects in human rheumatoid fibroblast-like synoviocytes (FLS). SPA0537 inhibited the nuclear translocation and the DNA binding of NF-{kappa}B subunits, which correlated with the inhibitory effects on IKK phosphorylation and I{kappa}B{alpha} degradation in TNF-{alpha}-stimulated rheumatoid FLS. These events further suppressed chemokine production, matrix metalloproteinase secretion, and TNF-{alpha}-induced cell proliferation. In addition, SPA0537 inhibited the osteoclast differentiation induced by macrophage colony-stimulating factor (MCSF) and receptor activator of the NF-{kappa}B ligand (RANKL) in bone marrow macrophages. These findings suggest that SPA0537 exerts anti-inflammatory effects in rheumatoid FLS through the inhibition of the NF-{kappa}B pathway. Therefore, it may have therapeutic value for the treatment of rheumatoid arthritis.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Caveolae/lipid rafts in fibroblast-like synoviocytes: ectopeptidase-rich membrane microdomains

    DEFF Research Database (Denmark)

    Riemann, D; Hansen, Gert Helge; Niels-Christiansen, L;

    2001-01-01

    from about 60 to 160 nm. Cholesterol depletion of synoviocytes by methyl-beta-cyclodextrin disrupted >90% of the caveolae and reduced the raft localization of aminopeptidase N/CD13 without affecting Ala-p-nitroanilide-cleaving activity of confluent cell cultures. In co-culture experiments with T...

  13. mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin

    DEFF Research Database (Denmark)

    Andreassen, Stine Mandrup; Berg, Lise Charlotte; Nielsen, Søren Saxmose;

    2015-01-01

    to lipopolysaccharide (LPS), fibrinogen and thrombin. Synovial membranes were collected from metacarpo-phalangeal joints of 6 skeletally mature horses euthanized for non-orthopaedic reasons. Passage 4 fibroblast-like synoviocytes were left non-treated or treated with either 0.1 μ g/ml LPS, 5 mg/ml fibrinogen or 5 U...... in increased mRNA expression of SAA, IL-6, MCP-1 and PAI-1, and a decreased PAR-1 expression compared to non-treated cells. The fibrinogen-treated synoviocytes showed significantly increased mRNA expression of IL-6, MCP-1, TF and PAI-1, and decreased PAR-1 expression compared to non-treated cells. Conclusion......: LPS, fibrinogen and thrombin induced an increased gene expression of inflammatory markers in isolated equine fibroblast-like synoviocytes. LPS caused changes in gene expression promoting increased fibrinolysis, while fibrinogen and thrombin changed the gene expression resulting potentially in reduced...

  14. Mast cells and fibroblast-like synoviocytes co-culture increases interleukin-6 secretion in rheumatoid arthritis%肥大细胞和类风湿关节炎成纤维样滑膜细胞共培养对白细胞介素-6分泌的影响

    Institute of Scientific and Technical Information of China (English)

    穆荣; 徐大模; 栗占国

    2008-01-01

    Objective To explore the significance of mast cells-fibroblast like synoviocytes (FLS) interaction in the pathogenesis of rheumatoid arthritis (RA). Methods Frozen sections of RA synovia from 4 patients were made to observe the distribution of mast cells by immunochemistry. FLSs were isolated from 4 samples of RA synovia and co-cultured with the human mast cells of the line LAD-2 for 0,12, 24, and 48h, and 7 d. ELISA was used to detect the interleukin (IL)-6, an important proinflammatory cytokine. 4%formaldehyde was used to fix the FLS and LAD-2 cells and then detect the IL-6 levels in the supernatant.Other FLS and LAD-2 mast cells were put into the upper and lower chambers of Transwell system to be cocultured in isolate condition, an important proinflammatory cytokine. Results Microscopy showed that FLSs were adjacent to the mast cells. The IL-6 content of the FLS/LAD-2 cell co-culture supernatant was 7150μg/L±114 μg/L, significantly higher than that of the FLS supernatant (3019 μg/L±57 μg/L, P<0.01). LAD-2 cell number dose-dependently increased the IL-6 content in the supernatant. Almost no IL-6secretion was found in the supernatant of the co-culture with fixed FLSs and non-fixe4d LAD-2 cells, and the IL-6 secretion in the supernatant of the c0-culture with fixed LAD-2 cells and non-fixed FLSs was similar to that of the single FLS group and far lower than that of the FLS-LAD-2 co-cuhure group. Transwell system test showed that there was no significant difference in the IL-5 level between the direct mixture co-culture group and indirect mixture co-culture. Conclusion Mast cell/FLS interaction increases the IL-6 secretion via soluble mediators, thus playing an important role in the pathogenesis of RA.%目的 观察肥大细胞和关节成纤维样滑膜细胞(FLS)共培养对FLS分泌白细胞介素(IL)-6的影响及其作用机制.方法 应用免疫组化染色法观察肥大细胞在关节滑膜中的分布.分离培养RA患者

  15. Fractalkine对类风湿关节炎患者成纤维样滑膜细胞中NF-κB活化及内源性fractalkine mRNA表达的影响%Effects of fractalkine on nuclear factor-κB activation and endogenous fractalkine mRNA expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    郭兴华; 潘云峰; 宋泽蓉; 王昆; 古洁若

    2011-01-01

    目的:观察Fractalkine(FKN)对类风湿关节炎(RA)患者成纤维样滑膜细胞(FLS)核转录因子κB (NF-κB)活化以及内源性FKN mRNA表达的影响.方法:通过组织块法培养RA-FLS.在RA-FLS中加入100 μg/L FKN,分别作用0 h、1 h及2 h,用Western blotting检测RA-FLS胞浆及胞核中NF-κB p65蛋白表达量变化以明确NF-κB的活化情况;加入100 μg/L重组人FKN分别作用0 h、12 h、18 h后,用RT-PCR检测FKN mRNA表达的变化.结果:重组人FKN刺激1 h后,RA-FLS胞浆中NF-κB p65蛋白水平明显低于无FKN刺激的对照组(P<0.05);FKN刺激后2 h,细胞核中NF-κB p65蛋白水平较对照组明显升高(P<0.05).100 μg/L重组人FKN刺激RA-FLS,呈时间依赖方式诱导内源性FKN mRNA表达.FKN刺激RA-FLS18 h,细胞中FKN mRNA的表达水平明显升高(P<0.05).结论:外源FKN可刺激RA-FLS内源性的FKN mRNA表达上升,提示RA-FLS中可能存在FKN的正反馈现象.FKN对NF-κB有活化作用,可能对RA患者关节中炎症的启动、血管生成和骨质破坏有重要作用.%AIM: To investigate the effects of fractalkine( FKN ) on nuclear factor kappa B ( NF - kB ) activation and endogenous FKN mRNA expression in fibroblast - like synoviocytes ( FLS ) from the patients with rheumatoid arthritis ( RA ). METHODS: RA - FLS were gained through tissue culture. Fractalkine at 100 μg/L was used to stimulate RA - FLS for 0 h, 1 h and 2 h. The expression of NF - kB p65 protein in cytoplasm and nucleus was detected by Western blotting, representing the activation of NF - kB in RA - FLS. RA - FLS was stimulated with fractalkine at concentration of 100 μg/L for 0 h, 12 h or 18 h, and the mRNA expression of FKN in RA - FLS was detected by RT - PCR. RESULTS: After stimulated with recombinant human FKN for 1 h, the expression of NF - kB p65 protein in the cytoplasm of RA - FLS was obviously lower than that in RA - FLS without FKN treatment in control group ( P <0. 05 ). After stimulated with FKN for 2 h, the

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

    NARCIS (Netherlands)

    Steenvoorden, Marjan Maria Claziena

    2007-01-01

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

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

    NARCIS (Netherlands)

    Steenvoorden, Marjan Maria Claziena

    2007-01-01

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

  18. Interleukin-1 receptor antagonist intervenes in signaling between different types of synoviocytes in rats with adjuvant arthritis

    Institute of Scientific and Technical Information of China (English)

    Yong-qiu ZHENG; Wei WEI; Min DAI; Lei ZHU; Xiao-yi JIA; Yuan WANG

    2006-01-01

    Aim: To investigate the mechanisms of interleukin-1 receptor antagonist (IL-1ra)in the treatment of adjuvant arthritis (AA). Methods: AA was induced in rats by treatment with Freund's complete adjuvant (FCA). Rats were given an intracutaneous injection of IL-1ra (2.5, 10, 40 mg/kg, 3 times per day) from d 14 to d 21 after immunization. Synoviocyte proliferation and the activity of IL-1 were determined by using MTT assay. Tumor necrosis factor alpha (TNF-α) and prostaglandin E2(PGE2) concentrations were measured by radioimmunoassay. The ultrastructure of synoviocytes was observed by using a transmission electron microscope.Phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase were detected by Western blot analysis. Results: IL-1ra (10and 40 mg/kg, ic, d 14-21) modulated the secondary inflammatory reaction (P<0.01), ultrastructure of synoviocytes and mitogen-activated protein kinase (MAPK) phosphorylation in AA rats. The administration of IL-1ra (10 and 40mg/kg, ic, d 14-21) in AA rats significantly decreased the production of IL-1, PGE2and TNF-α by macrophage-like synoviocytes (MLS) (P<0.01). IL-1 ra (2.5 mg/kg)also decreased the production of PGE2 (P<0.01) and TNF-α(P<0.05) by MLS in AA rats. The increased phosphorylation of MAPK and cell proliferation in fibroblast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats was also inhibited by IL-1ra (10 and 40 mg/kg, ic, d 14-21). Conclusion: IL-1ra has anti-inflammatory effects because it modulates the ultrastructure of synoviocytes,decreases the production of pro-inflammatory mediators by MLS, and inhibits the phosphorylation of MAPK in FLS.

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

    Directory of Open Access Journals (Sweden)

    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

  20. The anti-inflammatory effect of cyclooxygenase inhibitors in fibroblast-like synoviocytes from the human temporomandibular joint results from the suppression of PGE2 production

    Science.gov (United States)

    Kawashima, Mutsumi; Ogura, Naomi; Akutsu, Miwa; Ito, Ko; Kondoh, Toshirou

    2013-01-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the management of pain and inflammation. However, little remains known about the effects of NSAIDs on synovitis of the human temporomandibular joint (TMJ). The aims of this study were to investigate the potential anti-inflammatory effects of NSAIDs on synovitis of the TMJ and the inflammatory effects of PGE2 on fibroblast-like synoviocytes (FLS) derived from the TMJ. Methods Human synovial tissue was obtained from patients with internal derangement who underwent arthroscopy of the TMJ. FLSs were prepared from the tissues using the outgrowth method. A COX inhibitor (indomethacin or celecoxib) was added to the IL-1β-stimulated cells in culture. The cells were also stimulated with PGE2 or an EP agonist. The PGE2 production and COX-2 and IL-6 expression levels were examined using enzyme-linked immunosorbent assays, real-time PCR, and a microarray analysis. Results COX inhibitors decreased not only PGE2 production, but also the expression of COX-2 and IL-6 in FLS stimulated with IL-1β. EP2 and EP4 were both expressed in the FLS, and the treatment with EP2 and EP4 agonists induced IL-6 production in these cells. Conclusion The COX inhibitors indomethacin and celecoxib reduce the expression of inflammatory factors, such as COX-2 and IL-6, in FLS from the TMJ via suppression of PGE2 production. EP2 and EP4 were the main receptors for PGE2 present in the FLS. The approach used in this study may be useful for revealing how drugs such as NSAIDs affect the cellular functions of FLS from the TMJ. PMID:23331485

  1. Intracellular delivery of poly(I:C) induces apoptosis of fibroblast-like synoviocytes via an unknown dsRNA sensor

    Energy Technology Data Exchange (ETDEWEB)

    Karpus, Olga N.; Hsiao, Cheng-Chih; Kort, Hanneke de; Tak, Paul P.; Hamann, Jörg, E-mail: j.hamann@amc.uva.nl

    2016-08-26

    Fibroblast-like synoviocytes (FLS) express functional membranous and cytoplasmic sensors for double-stranded (ds)RNA. Notably, FLS undergo apoptosis upon transfection with the synthetic dsRNA analog poly(I:C). We here studied the mechanism of intracellular poly(I:C) recognition and subsequent cell death in FLS. FLS responded similarly to poly(I:C) or 3pRNA transfection; however, only intracellular delivery of poly(I:C) induced significant cell death, accompanied by upregulation of pro-apoptotic proteins Puma and Noxa, caspase 3 cleavage, and nuclear segregation. Knockdown of the DExD/H-box helicase MDA5 did not affect the response to intracellular poly(I:C); in contrast, knockdown of RIG-I abrogated the response to 3pRNA. Knockdown of the downstream adaptor proteins IPS, STING, and TRIF or inhibition of TBK1 did not affect the response to intracellular poly(I:C), while knockdown of IFNAR blocked intracellular poly(I:C)-mediated signaling and cell death. We conclude that a so far unknown intracellular sensor recognizes linear dsRNA and induces apoptosis in FLS. - Highlights: • Intracellular poly(I:C) and 3pRNA evoke immune responses in FLS. • Only intracellular delivery of poly(I:C) induces FLS apoptosis. • FLS do not require MDA5 for their response to intracellular poly(I:C). • FLS respond to intracellular poly(I:C) independent of IPS and STING. • An unknown intracellular sensor recognizes linear dsRNA in FLS.

  2. 双向电泳和质谱技术在类风湿关节炎滑膜细胞差异蛋白分析中的应用及意义%Screening differentially expressed proteins of fibroblast-like synoviocytes in rheumatoid arthritis by 2-DE and MALDI-TOF-MS

    Institute of Scientific and Technical Information of China (English)

    赵晓琴; 李晓军; 赵建宁; 庞小娟; 陈芳芳; 虞伟; 罗冰

    2010-01-01

    Objective To identify synovium-associated proteins of by analyzing proteome of FLS between RA patients and traumatic arthritis. Methods The total protein of FLS from 3 patients of RA and 6 normal controls were separated by 2-DE. The differentially expressed proteins were identified by MALDI-TOF-MS. Results The 2-DE image results showed that there were many proteins differentially expressed in FLS from RA and control. A total of 33 differential proteins that were up-regulated in RA as compared with controls were selected and 30 proteins including pyruvate kinase isozymes M1/M2, α-enolase, protein disulfide-isomerase A3 precursor, glutathione transferase, peroxiredoxin 1, ubiquitin-conjugating enzyme E2K, platelet-activating factor acetylhydrolase IB, dihydropyrimidinase-related protein 2, adenosine kinase, transaldolase, δ-δ-dienoyl-CoAisomerase, 26S protease regulatory subunit 6A, annexin All, tryptophanyl-tRNA synthetase isoform b, lamin-A/C, myomesin-1 isoform b, ruvB-like 1, actin-cytoplasmic 1, T-complex protein 1, stress-70 protein, mitochondrial precursor, α-crystallin B chain, 78 000 glucose-regulated protein, PSME4, SELENBP1 and so on. Conclusion The differentially expressed proteins are present in FLS from RA and control, which may be the synovium biomakers and involved in pathogenesis of RA.%目的 采用2-DE和质谱技术分析RA患者和创伤件关节炎患者关节滑膜组织中FLS蛋白质组学的变化,寻找RA关节滑膜特异性自身抗原.方法 采用2-DE分离6例创伤性关节炎患者及3例RA患者关节滑膜组织中FLS总蛋白质,凝胶经银染显色和图像数据分析识别差异蛋白质点,并用MALDI-TOF-MS对筛选出的差异蛋白质点进行鉴定.结果 RA患者与创伤性关节炎患者中的FLS蛋白质通过2-DE检测,分别检出1 633、1 603个蛋白质点;对2组相互匹配的蛋白质点进行差异分析后,其中蛋白质差异量大于3倍的差异点共有92个,从中选

  3. [Collagenase production increases in rheumatoid arthritis and osteoarthritis synoviocytes incubated].

    Science.gov (United States)

    Montrull, H L; Brizuela, N Y; Demurtas, S L; Strusberg, A M; Spitale, L S; Meirovich, C I

    2000-01-01

    Cartilage is a specialized connective tissue. It contains few cells into an extracell matrix. The matrix mainly constituents are collagen and proteoglycans. Its degradation depends on synoviocytes activity, that secrete metalloproteases, agents to proteoglycans catabolism. There are two types of synoviocytes: macrophagics (type "A:') and fibroblastics (type "B"). The proteoglycan destruction can be LT-dependent or LT-independent. The aim of this work is synoviocytes function ex vívo study, free immune system influence. In order to do it, heparinized synovial fluid samples were obtained from 6 osteoarthritic (OA) and 6 arthritic (RA) both sex untreated patients, diagnosed according ACR criteria, which disease duration was longer than 6 months. Patients average age was 70 +/- 2 years. Control samples were synovial fluid from traumatic arthritis or non inflammatory bone-muscle pathology. Synovial fluid was centifugated at 1500 g for 30 minutes to isolate synoviocytes. Sediment containing cells was 6 hs incubed with Dulbecco-Eagles media, that has HEPES Gibco (26 mM); NaHCO3 (0.5 g/I); glutamine (2 mM), streptomicine (100 mg/l), G-penicillin (1 U/ml); anphotericine B (2.5 mg/l). Cells calification and viability were cytopathologically determined. Before and after incubation, collagenase activity was measured by ELISA-double-sandwich, using 10 micrograms/ml monoclonal anti-MMPs in phosphate-buffer-saline. The antigen-antibody complex production with inespecific proteins was blocked by bovine seric albumine. Streptavidin peroxidase was added and washed with 2,2,azin,di(3-ethyl-benztazoilinsuiphonic) acid to develop color. The link of labeled antibody by absorbance at 410 nm was determined in ELISA-spectrophothometer. RA patients earlier MMPs synoviocytes production was 1373 +/- 115 ng/ml. Then 6 hs incubation 2143 +/- 132 ng/ml was reached. The increase (56%) had high significance (p cartilago, because SF provides markers of joint disease. MMPs are giving information

  4. 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.

  5. 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.

  6. The Ras guanine nucleotide exchange factor RasGRF1 promotes matrix metalloproteinase-3 production in rheumatoid arthritis synovial tissue

    NARCIS (Netherlands)

    de Abreu, J.R.F.; de Launay, D.; Sanders, M.E.; Grabiec, A.M.; van de Sande, M.G.; Tak, P.P.; Reedquist, K.A.

    2009-01-01

    Introduction Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis ( RA) patients share many similarities with transformed cancer cells, including spontaneous production of matrix metalloproteinases ( MMPs). Altered or chronic activation of proto-oncogenic Ras family GTPases is thought to

  7. Superantigen-induced collagenase gene expression in human IFN-{gamma}-treated fibroblast-like synoviocytes involves prostaglandin E{sub 2}: Evidence for a role of cyclooxygenase-2 and cytosolic phospholipase A{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Mehindate, K; Al-Daccak, R.; Mourad, W. [Laval Univ., Ste-Foy, Quebec (Canada)] [and others

    1995-10-01

    MHC class II molecules expressed in lymphoid and nonlymphoid cells act as signal-transducer molecules. We demonstrate that engagement of MHC class II molecules on human IFN-{gamma}-treated fibroblast-like synoviocytes by their natural ligand, the staphylococcal enterotoxin A (SEA), selectively induces the production of interstitial collagenase over the expression of the tissue inhibitor of metalloproteinase (TIMP). Collagenase gene expression required de novo protein synthesis and was accompanied by high levels of PGE{sub 2} production, suggesting its implication in this response. Two inhibitors that affect prostaglandin biosynthesis, indomethacin and arachidonyl-trifluoromethyl-ketone, inhibited both PGE{sub 2} production and collagenase gene expression. The addition of exogenous PGE{sub 2} to inhibitor-treated cells partially restored the SEA-induced collagenase, indicating a role for PGE{sub 2} in this response. As cyclooxygenases (COX-1 and -2), cytosolic phospholipase A{sub 2} (cPLA{sub 2}), and secreted PLA{sub 2} (sPLA{sub 2}) are the enzymes potentially implicated in prostaglandin synthesis, their involvement in SEA-induced collagenase was investigated. The mRNA levels of COX-2 and cPLA{sub 2} rapidly increased following ligation of MHC class II molecules, while COX-1 and sPLA{sub 2} mRNA levels were unchanged and transiently depressed, respectively. SEA-induced COX-2 mRNA was translated adequately to protein, whereas cPLA{sub 2} protein level was not enhanced, but rapidly phosphorylated, a process previously linked to the enzyme activation. In conclusion, this work demonstrates a selective induction of collagenase gene expression over its natural inhibitor TIMP in human IFN-{gamma}-treated fibroblast-like synoviocytes mediated, at least in part, by PGE{sub 2}, and provides evidence that signaling via MHC class II molecules induces the production of PGE{sub 2} through enhanced production of COX-2 and possibly activation of the cPLA{sub 2}. 46 refs., 10 figs.

  8. Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-{kappa}B acetylation in fibroblast-like synoviocyte MH7A cells

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Ah-Reum; Yoo, Jung-Yoon; Choi, KyungChul [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Lee, Mee-Hee [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of); Lee, Yoo-Hyun [Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do (Korea, Republic of); Lee, Jeongmin [Department of Medical Nutrition, Kyung Hee University, Kyunggi-do (Korea, Republic of); Jun, Woojin [Department of Food and Nutrition, Chonnam National University, Gwangju (Korea, Republic of); Kim, Sunoh, E-mail: sunoh@korea.ac.kr [Jeollanamdo Institute of Natural Resources Research, Jeonnam (Korea, Republic of); Yoon, Ho-Geun, E-mail: yhgeun@yuhs.ac [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

    2011-07-08

    Highlights: {yields} Delphinidin is a novel inhibitor of p300/CBP histone acetyltransferase. {yields} Delphinidin prevents the hyperacetylation of p65 by inhibiting the HAT activity of p300/CBP. {yields} Delphinidin efficiently suppresses the expression of inflammatory cytokines in MH7A cells via hypoacetylation of NF-{kappa}B. {yields} Delphinidin inhibits cytokine release in the Jurkat T lymphocyte cell line. -- Abstract: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKB{alpha}. Accordingly, DP treatment inhibited TNF{alpha}-stimulated increases in NF-{kappa}B function and expression of NF-{kappa}B target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.

  9. Effects of Resveratrol on the Proliferation and Apoptosis in Synoviocytes of Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    唐玲丽; 余平; 胡敏; 谢希; 陈新瑞

    2004-01-01

    This study was undertaken to investigate the regulatory effect of Resveratrol (Res) on the proliferation and apoptosis of synoviocytes of patients with rheumatoid arthritis (RA), as the proliferation of synoviocytes of patients was determined by MTT chromatometry and the apoptosis of these cells was assayed with TUNEL flow cytometry. It was found in this experiment that the degree of cell proliferation of the Res-treated group with dosages of 50-400 μM was significantly reduced in comparison with that of the control group, but percentage of the apoptotic cells demonstrated with TUNEL labeling was elevated under treatment with Res at the same dosages in a concentration-dependent manner. The difference between the Restreated group and the control group was quite significant ( P<0.01 ). It is concluded that Res shows a potent anti-proliferative effect on synoviocytes of patients with RA with induction of cell apoptosis, and it is likely a valuable candidate for the chemotherapy and management of patients with RA.

  10. 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.

  11. 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.

  12. Reduction of interleukin-6 expression in human synoviocytes and rheumatoid arthritis rat joints by linear polarized near infrared light (Superlizer) irradiation.

    Science.gov (United States)

    Araki, Hidefumi; Imaoka, Asayo; Kuboyama, Noboru; Abiko, Yoshimitsu

    2011-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disorder that involves inflammation and pain of joints. Low-level laser irradiation is being evaluated for treating RA, however, the effectiveness of linear polarized near infrared light (SuperLizer; SL) irradiation is unclear. It has been reported that interleukin 6 (IL-6) plays a key role in the progression of RA. In our previous study, using DNA microarray analysis, we examined the gene expression profiling of human rheumatoid fibroblast-like synoviocyte MH7A in response to IL-1ß administration and SL irradiation. As a result, IL-6 was listed in altered gene as increased by IL-1ß and decreased by SL irradiation. The reduction of IL-6 gene expression in MH7A by SL irradiation was confirmed by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. Effect of SL irradiation on the RA inflammation in the collagen induced arthritis (CIA) rats was also studied by measuring temperature. IL-6 production in knee joint of rats was analyzed by immunohisto-chemistry. Scatter plot analysis demonstrated that an increase in IL-6 gene expression by IL-1ß was reduced by SL irradiation. The reduction of IL-6 mRNA level by SL irradiation was successfully confirmed by RT-PCR and real-time PCR. SL irradiation treated CIA rat decreased the temperature of knee joints. The immunohistochemical analysis demonstrated a strong IL-6 staining in synovial membrane tissue of CIA rat joint, and SL irradiation significantly reduced the staining. Since IL-6 has been identified to be an important proinflarnmatory cytokine in the pathogenesis of RA, the reduction of IL-6 expression is one of mechanisms in reduction of inflammation in RA joints by SL irradiation suggesting that SL irradiation may be useful for RA therapy. SL irradiation reduced IL-6 gene expression in MH7A, and reduced inflammation and IL-6 protein expression in knee joint of CIA rats.

  13. IL-17A and TNF-α Increase the Expression of the Antiapoptotic Adhesion Molecule Amigo-2 in Arthritis Synoviocytes

    Science.gov (United States)

    Benedetti, Giulia; Bonaventura, Paola; Lavocat, Fabien; Miossec, Pierre

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disorder, characterized by a persistent immune cell infiltrate in the synovium accompanied by high levels of inflammatory mediators and synovial hyperplasia. Despite significant therapeutic advances, RA remains an important unmet medical need. To discover potential new genes controlling inflammation and apoptosis in synoviocytes, genes induced by the two pro-inflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 17A (IL-17A), were systematically searched. We identified Amphoterin-induced gene and ORF 2 (Amigo-2), a novel antiapoptotic adhesion molecule, as synergistically upregulated by the IL-17A/TNF combination specifically in RA synoviocytes. In addition, when RA synoviocytes were cocultured with immune cells, Amigo2 expression was significantly increased in both fibroblasts and immune cells. This induction persisted in RA synoviocytes even after the removal of the immune cells. Amigo2 induction was ERK-dependent and on the contrary, inhibited by JNK. Furthermore, Amigo2 expression levels correlated with apoptosis of the cells when exposed to the proapoptotic agent cadmium (Cd). Interestingly, exposure of the cells to HMGB1 in inflammatory conditions increased synergistically Amigo2 expression and significantly reduced Cd-mediated cellular toxicity. Our findings support a model whereby cell–cell contact with immune cells and exposure to the combination of both inflammatory cytokines and HMGB1 in the joints of RA patients increases Amigo2 expression in synoviocytes in an ERK-dependent manner which, in turn, enhances cellular adhesion and promotes cell survival and cellular proliferation. PMID:27446084

  14. Therapeutic Actions of the Chinese Herbal Formulae with Cold and Heat Properties and Their Effects on Ultrastructures of Synoviocytes in Rats of the Collagen-Induced Arthritis

    Institute of Scientific and Technical Information of China (English)

    李梢; 吕爱平; 贾宏伟

    2002-01-01

    The therapeutic actions of Qing Luo Yin (QLY清络饮) with heat property and Wen Luo Yin (WLY温络饮) with cold property on pain, swelling of the ankle, arthritis index and ultrastructures of synoviocytes were compared in rats of type II collagen-induced arthritis (CIA), with tripterygium glycosidorum (TG) used as control. The results indicated that both QLY and WLY could reduce pain, swelling of the ankle and the arthritis index of CIA, and QLY had better effects in reducing the swelling of the ankle and controlling the secondary pathological lesions as compared with WLY. Investigation on the ultrastructures of synoviocytes indicated that both QLY and WLY could reduce the number of Golgi apparatus, rough surface endoplasmic reticulum, dense bodies, matrix filaments and vacuoles so as to suppress the excessive secretion of synoviocytes in rats of CIA.

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

    DEFF Research Database (Denmark)

    Ribel-Madsen, Søren; Bartels, Else Marie; Stockmarr, Anders

    2012-01-01

    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......, 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...

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

    NARCIS (Netherlands)

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

    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.

  17. 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 (...

  18. 15-deoxy-Δ12,14-PGJ2 induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats

    Science.gov (United States)

    Kawahito, Yutaka; Kondo, Motoharu; Tsubouchi, Yasunori; Hashiramoto, Akira; Bishop-Bailey, David; Inoue, Ken-ichiro; Kohno, Masataka; Yamada, Ryoji; Hla, Timothy; Sano, Hajime

    2000-01-01

    Peroxisome proliferator–activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and have a dominant regulatory role in adipocyte and monocyte differentiation. PPAR-γ agonists are also negative regulators of macrophage activation and have modulatory effects on tumorigenesis. In this study we demonstrate that synovial tissue localized expression of PPAR-γ in patients with rheumatoid arthritis (RA). We detected markedly enhanced expression of PPAR-γ in macrophages, as well as modestly enhanced expression in the synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR-γ by 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and the synthetic PPAR-γ ligand (troglitazone) induced RA synoviocyte apoptosis in vitro. Moreover, intraperitoneal administration of these PPAR-γ ligands ameliorated adjuvant-induced arthritis with suppression of pannus formation and mononuclear cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ2 were more potent than troglitazone. These findings suggest that PPAR-γ may be an important immunoinflammatory mediator and its ligands, especially 15d-PGJ2, may be useful in the treatment of RA. PMID:10903334

  19. 金雀异黄素对类风湿关节炎患者成纤维样滑膜细胞骨保护素/细胞核因子κB受体活化因子/细胞核因子κB受体活化因子配体通路的影响%Effect of Genistein on the Osteoprotegerin/Receptor-activator of Nuclear Factor Kappa Bata/Receptor-activator of Nuclear Factor Kappa Bata Ligand System of Fibroblast-like Synoviocytes

    Institute of Scientific and Technical Information of China (English)

    王燕茹; 张育; 沈维干; 尚辰; 马莹莹; 方振玉

    2013-01-01

    目的 研究金雀异黄素(genistein,Gen)对人类风湿关节炎(rheumatoid arthritis,RA)成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)骨保护素(osteoprotegerin,OPG)/细胞核因子κB受体活化因子(receptor-activator of nuclear factor kappa bata,RANK)/细胞核因子κB受体活化因子配体(receptor-activator of nuclear factor kappa bata ligand,RANKL)通路的影响及机制.方法 培养人RA-FLS,并分为对照组(RA-FLS细胞)、TNF-α组(RA-FLS细胞+TNF-α 10 ng/ml)、TNF-α+ Gen组(RA-FLS细胞+TNF-α 10 ng/ml+ Gen 50 μM)、Gen组(RA-FLS细胞+Gen 50 μM).应用免疫印迹检测Gen作用RA-FLS的RANK、RANKL、OPG、雌激素受体(estrogen receptor α,ERα)表达情况,免疫荧光检测ERα细胞内分布情况.结果 Gen组、TNF-α组及TNF-α+ Gen组细胞内RANK蛋白表达量较对照组无明显差异(P>0.05),但OPG及RANKL蛋白表达明显高于对照组(均P<0.05).Gen组OPG/RANKL较对照组增高(P<0.05).Gen组、TNF-α组及TNF-α+ Gen组细胞内ERα蛋白表达量与对照组比较,差异无统计学意义(P>0.05).免疫荧光结果显示核内ERα表达量增加.结论 Gen可能通过与雌激素受体结合,转入核内发挥免疫调节作用,从而调节OPG/RANKL/RANK通路,发挥抑制骨破坏的作用.Gen可以上调人RA-FLS中OPG及RANKL,且对OPG的上调作用更强.

  20. Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ling-ling; WEI Wei; WANG Qing-tong; CHEN Jing-yu; CHEN Yin

    2008-01-01

    Background Signaling pathways that regulate the production of cytokines and destructive enzymes have been implicated in rheumatoid arthritis (RA) pathogenesis.There are co-relations between signaling pathways.The aim of this study was to investigate interactions and cross-talks between MEK1/2-extracellular signal-related kinase (ERK1/2)signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis (CIA) rats by the stimulation of interleukin-1 (IL-1),U0126,isoprenaline hydrochloride and aminophyline respectively.Methods Twenty Sprague-Dawley (SD) rats were induced by chicken type Ⅱ collagen.Synoviocytes of CIA rats were isolated and cultured.The expressions of Gi,phosphorylated MEK1/2 (p-MEK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting.cAMP level and protein kinase A (PKA) activity were measured by radioimmunoassay and kinase-glo(R) luminescent kinase assay respectively.Results There was remarkable inflammation in CIA rats accompanied by swelling paws,hyperplastic synovium,pannus and cartilage erosion,cAMP level and PKA activity of synoviocytes decreased.Gi,p-ERK1/2 and p-MEK1/2 increased,rIL-1α improved the expression of Gi,p-ERK1/2 and p-MEK1/2,cAMP and PKA increased with stimulation of rIL-1α.U0126 inhibited Gi,cAMP and PKA of synoviocytes stimulated by rIL-1α.Isoprenaline hydrochloride enhanced Gi,cAMP and PKA,but had no effects on p-MEK1/2 and p-ERK1/2.Aminophyline increased cAMP and PKA,but inhibited p-MEK1/2 and p-ERK1/2.Conclusions Mitogen-activated protein kinases (MAPKs) and G protein-couple signaling are associated with synovitis.There are cross talks between MAPKs and G protein-couple signaling.The two signaling pathways represent potential therapeutic targets for RA.

  1. Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages

    OpenAIRE

    Matsumoto, Takuya; Takahashi, Nobunori; Kojima, Toshihisa; Yoshioka, Yutaka; Ishikawa, Jun; Furukawa, Koichi; Ono, Kenji; Sawada, Makoto; ISHIGURO, NAOKI; Yamamoto, Akihito

    2016-01-01

    Background The aim of this study was to assess the effects of soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 on joint inflammation and destruction in a murine collagen-induced arthritis (CIA) model and in monolayer cultures of murine macrophages (RAW264.7 cells and peritoneal macrophages) and fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis. Methods DBA/1J mice were immunized with type II collagen. Effects of sSiglec-9 were evaluated using...

  2. Evaluation of the anti-inflammatory effects of steroids and arthritis-related biotherapies in an in vitro co-culture model with immune cells and synoviocytes

    Directory of Open Access Journals (Sweden)

    Melissa Noack

    2016-11-01

    Full Text Available Background: During rheumatoid arthritis (RA, steroids and biotherapies are used alone and combined. Efficacy has been established in clinical trials but their differential effects at the cellular level are less documented. The aim was to study these cellular effects using an in vitro model with synoviocytes interacting with peripheral blood mononuclear cells (PBMC to reproduce the interactions in the RA synovium.Methods: Activated-PBMC were co-cultured with RA synoviocytes during 48h. A dose-response of methylprednisolone (MP was tested and different biotherapies (Infliximab, Etanercept, Adalimumab, Tocilizumab, Abatacept and Rituximab were added alone or in combination with MP. Cytokine production (IL-17, IL-6, IL-1β, IFN-γ and IL-10 was measured by ELISA.Results: Addition of MP to co-cultures inhibited the production of all cytokines. The response to the biotherapies alone was treatment-dependent. IL-17 production was inhibited only by Tocilizumab (p=0.004 while IL-6 was decreased only by Infliximab (p≤0.002. IL-1β level was affected in all conditions (p≤0.03. IFN-γ production was mainly decreased by Infliximab (p=0.004, and IL-10 by Infliximab and Tocilizumab (p≤0.004. The combination MP and biotherapy did not induce an additional effect on pro-inflammatory cytokine inhibition. The combination MP and biotherapies induced a higher IL-10 secretion than MP alone, mainly with Rituximab.Conclusion: Steroids inhibited the secretion of all cytokines, and low doses were as potent. The anti-inflammatory effect of biotherapies was dependent on their mechanism of action. MP and biotherapy combination did not enhance the inhibitory effect on pro-inflammatory cytokines but could have a beneficial effect by increasing IL-10 production.

  3. PTEN在类风湿关节炎成纤维样滑膜细胞中的表达及意义%Expression and function of PTEN in fibroblast-like synoviocytes of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    吴云婷; 刘岩; 刘梦; 杨梦如; 莫碧瑶; 潘云峰

    2016-01-01

    目的:探讨第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)在人类风湿关节炎(RA)成纤维样滑膜细胞(FLS)中的表达水平及意义.方法:利用组织块法获得并体外培养人RA-FLS、骨关节炎(OA)-FLS及关节创伤-FLS;采用实时荧光定量PCR法检测各组FLS中PTEN mRNA表达水平的差异;采用Western blotting法检测各组FLS的PTEN蛋白表达水平以及Akt Thr308位点磷酸化水平的差异.结果:(1) RA-FLS中的PTEN mRNA表达水平显著低于OA-FLS及关节创伤-FLS(P <0.01),而OA-FLS与关节创伤-FLS之间的PTEN mR-NA表达水平无统计学差异.(2) RA-FLS的PTEN蛋白表达水平显著低于OA-FLS及关节创伤-FLS(P <0.05),而OA-FLS与关节创伤-FLS之间的PTEN蛋白表达水平无统计学差异.(3) RA-FLS中的Akt蛋白Thr308位点磷酸化水平显著高于OA-FLS及关节创伤-FLS(P<0.01),且OA-FLS中该位点的磷酸化水平显著低于关节创伤-FLS(P<0.01).(4) RA-FLS中的PTEN蛋白水平与Akt Thr308位点磷酸化水平呈显著负相关(P<0.01).结论:RA-FLS中PTEN基因呈低水平表达,可能与Akt Thr308位点磷酸化水平异常增高相关.

  4. Role of PGE2 and EP receptors in the pathogenesis of rheumatoid arthritis and as a novel therapeutic strategy.

    Science.gov (United States)

    Akaogi, Jun; Nozaki, Toshiko; Satoh, Minoru; Yamada, Hidehiro

    2006-12-01

    Recent progress in understanding the pathogenesis of rheumatoid arthritis (RA) in parallel with elucidation of the functional role of the prostaglandin receptor subfamily has revealed an important regulatory role of PGE2, in addition to its well-known proinflammatory role in the progression of RA. Characteristic features of RA are synovial proliferation and pannus formation, which result in the destruction of cartilage and bone. Pannus tissue is mainly composed of macrophages and fibroblast-like synoviocytes. Both T cell-derived IL-17 and macrophage-derived TNF-alpha seem to play a central role in the progression of proinflammatory cascades in RA. PGE2 is also produced in response to proinflammatory cytokines, which in turn negatively regulates both IL-17 and TNF-alpha expression and TNF/IL-1-induced activation of fibroblast-like synoviocytes through EP2/EP4 receptors, resulting in the modulation of proinflammatory cascades. IL-17- and TNF-activated macrophages differentiate into osteoclasts in the presence of M-CSF and RANKL expressed by fibroblast-like synoviocytes. PGE2 binding to EP4 stimulates osteoclastogenesis through enhancing RANKL expression. At the same time, PGE2 suppresses osteoclastogenesis by inhibiting M-CSF expression of fibroblast-like synoviocytes as well as both IL-17 and IL-17-induced TNF-alpha expression of macrophages. PGE2-EP4 also activates osteoblastogenesis through increasing cbfa1 and osterix, two essential transcription factors required for bone formation. The net effect of PGE2 may direct toward repair of eroding bone through the suppression of inflammation and enhancement of bone remodeling. Here, we discuss a diverse action of PGE2/EP receptors and their important regulatory roles in the pathogenesis of RA, which may lead to a novel therapeutic strategy.

  5. Cytosolic phospholipase A2 modulates TLR2 signaling in synoviocytes.

    Directory of Open Access Journals (Sweden)

    Randi M Sommerfelt

    Full Text Available Rheumatoid arthritis (RA is an autoimmune disease characterized by chronic synovitis leading to destruction of cartilage and bone. PLA2 enzymes are key players in inflammation regulating the release of unsaturated fatty acids such as arachidonic acid (AA, a precursor of pro-inflammatory eicosanoids. Several lines of evidence point to toll-like receptors (TLRs as drivers of synovitis and joint destruction in RA. However, few studies have addressed the implication of PLA2 activity downstream TLR activation in the synovium. Here, we aimed to characterize PLA2 enzyme involvement in TLR2-induced signaling in synovial fibroblast-like cells. TLRs1-7 and a range of sPLA2, iPLA2 and cPLA2 enzymes were found to be transcriptionally expressed in cultured synoviocytes. Activation of TLR2/1 and TLR2/6 led to phosphorylation of cPLA2α at Ser505, and induced AA release and PGE2 production; effects that were attenuated by cPLA2α inhibitors. In contrast, sPLA2 inhibitors did not affect AA or PGE2 release. cPLA2α inhibitors furthermore attenuated TLR-induced expression of IL-6, IL-8 and COX2. COX1/2 inhibitors attenuated TLR2/6-induced IL-6 transcription and protein production comparable to cPLA2α inhibition. Moreover, exogenously PGE2 added alone induced IL-6 production and completely rescued IL-6 transcription when added simultaneously with FSL-1 in the presence of a cPLA2α inhibitor. Our results demonstrate for the first time that cPLA2α is involved in TLR2/1- and TLR2/6-induced AA release, PGE2 production and pro-inflammatory cytokine expression in synoviocytes, possibly through COX/PGE2-dependent pathways. These findings expand our understanding of cPLA2α as a modulator of inflammatory molecular mechanisms in chronic diseases such as RA.

  6. The autotaxin-lysophosphatidic acid pathway in pathogenesis of rheumatoid arthritis.

    Science.gov (United States)

    Orosa, Beatriz; García, Samuel; Conde, Carmen

    2015-10-15

    Lysophosphatidic acid (LPA) is a phospholipid that is mainly produced by the hydrolysis of lysophosphatidylcholine (LPC) by lysophospholipase D, which is also called autotaxin (ATX). LPA interacts with specific G-protein coupled receptors and is involved in the regulation of cellular survival, proliferation, differentiation and motility. LPA also has roles in several pathological disorders, such as cancer and pulmonary, dermal and renal fibrosis. The involvement of the ATX-LPA pathway has recently been demonstrated in inflammatory responses and apoptosis of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis and during the development of experimental arthritis. This review summarises the current literature of the ATX-LPA pathway in rheumatoid arthritis.

  7. Caveolae in fibroblast-like synoviocytes: static structures associated with vimentin-based intermediate filaments

    DEFF Research Database (Denmark)

    Berg, Kasper; Tamas, Raluca; Riemann, Anne;

    2008-01-01

    -temporal fixation of caveolae clusters. RECK, a glycosylphosphatidylinositol-anchored protein acting as a negative regulator of cell surface metalloproteinases, was also localized to the caveolae clusters. We propose that these clusters function as static reservoirs of specialized lipid raft domains where proteins...

  8. Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of Lubricin’s suppression of Pro-inflammatory Cytokine Induced Synoviocyte Proliferation

    Science.gov (United States)

    Al-Sharif, Afnan; Jamal, Maha; Zhang, Ling; Larson, Katherine; Schmidt, Tannin; Jay, Gregory; Elsaid, Khaled

    2015-01-01

    Objective To evaluate recombinant human proteoglycan 4 (rhPRG4) binding to CD44 receptor and its consequence on cytokine induced synoviocyte proliferation. Methods rhPRG4 binding to CD44 and competition with high molecular weight hyaluronic acid (HMW HA) was evaluated using a direct enzyme linked immunosorbent assay (ELISA) and surface plasmon resonance. Sialidase-A and O-glycosidase digestion of rhPRG4 was performed and CD44 binding was evaluated using ELISA. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were stimulated with interleukin-1 beta (IL-1β) or tumor necrosis factor alpha (TNF-α) for 48 hours in the presence or absence of rhPRG4 or HMW HA at 20, 40 and 80μg/ml and cell proliferation was measured. CD44 contribution was assessed by co-incubation with a CD44 antibody (IM7). The anti-proliferative effect of rhPRG4 was investigated following treatment of Prg4−/− synoviocytes with IL-1β or TNF-α in the presence or absence of IM7. Results rhPRG4 binds CD44 and interferes with HMW HA CD44 binding. Removal of sialic acid and O-glycosylations significantly increased CD44 binding by rhPRG4 (p<0.001). rhPRG4 and HMW HA at 40 and 80μg/ml significantly suppressed IL-1β induced RA-FLS proliferation (p<0.05). rhPRG4 at 20, 40 and 80μg/ml significantly suppressed TNF-α induced RA-FLS proliferation (p<0.05). CD44 neutralization reversed the effect of rhPRG4 on IL-1β and TNF-α stimulated RA-FLS and the effect of HMW HA on IL-1β stimulated RA-FLS. rhPRG4 inhibited cytokine-induced proliferation of Prg4−/− synoviocytes which could be prevented by blocking CD44. Conclusion Lubricin is a novel putative ligand for CD44 and may control synoviocyte overgrowth in inflammatory arthropathies via a CD44-mediated mechanism. PMID:25708025

  9. Ginsenoside metabolite compound K exerts joint-protective effect by interfering with synoviocyte function mediated by TNF-α and Tumor necrosis factor receptor type 2.

    Science.gov (United States)

    Wang, Ying; Chen, Jingyu; Luo, Xuexia; Zhang, Ying; Si, Ming; Wu, Huaxun; Yan, Chang; Wei, Wei

    2016-01-15

    Ginsenoside metabolite compound K (CK), metabolite of the ginsenoside, is considered to exert numerous pharmacological efficacies of ginsenoside, including anti-inflammation and immunoregulatory effects. Rheumatoid arthritis (RA) is a multi-systemic autoimmune disease characterized by hyperplastic synovial membrane and systemic inflammation, which ultimately lead to progressive destructive inflammatory arthropathy. To evaluate the potential joint-protective effects of CK and the underlying mechanism, adjuvant arthritis (AA) was induced by complete Freund's adjuvant in rats. After the onset of arthritis, The effect of CK on AA rats was evaluated by histopathology of the joint. The proliferation of fibroblast-like synoviocyte(FLS) was assayed by the Cell Counting Kit-8.The migration of FLS was assayed by transwell migration assay. Cytokines in the supernatant from FLS were measured by ELISA kit. Expression of Tumor Necrosis Factor Receptor Type 1(TNFR1) and Tumor Necrosis Factor Receptor Type 2(TNFR2) were detected by immunostaining analysis and western blot analysis. CK (80mg/kg) significantly ameliorated the histopathological change of joint in AA rats, balanced the RANKL/OPG ratio and attenuated the proliferation and migration of AA-FLS. CK suppressed the secretion of proinflammatory cytokines TNF-α and downregulated the expression of TNFR2 on AA-FLS. In vitro CK also significantly suppressed proliferation, migration and secretion of AA-FLS mediated by TNF-α. Further studies showed that the effects of CK on AA-FLS were reversed by using glucocorticoid receptor (GR) antagonist (mifepristone). Our data suggest that CK exerts joint-protective effect by interfering with synoviocyte function mediated by TNF-α and TNFR2, and this effect may be mediated by GR.

  10. 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

  11. Isorhamnetin attenuates collagen-induced arthritis via modulating cytokines and oxidative stress in mice.

    Science.gov (United States)

    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 (LPS) and isorhamnetin. The severity of arthritis was assessed by arthritis score, joint destruction score and inflammation score. Levels of cytokines TNF-α, IL-1β, IL-6, IL-17A, IL-17F, IL-10 and IL-35 in the joint tissue homogenate and cell culture medium as well as anti-type II collagen antibody in serum were measured using ELISA. Contents of H2O2 and malondialdehyde (MDA) in joint tissue homogenate were measured using assay kits. We found collagen immunization induced significant arthritis in mice and isorhamnetin at the dose of 10 and 20 mg/kg/day could significantly attenuate the collagen-induced arthritis. Isorhamnetin also modulated the production of cytokines and suppressed the oxidative stress in the mice with collagen-induced arthritis at the dose of 10 and 20 mg/kg/day. These data suggested that isorhamnetin might be a potential agent for the management of RA.

  12. 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.

  13. Effects of TREM-2 silencing on migration and invasion abilities of rheumatoid arthritis fibroblast-like synoviocytes%沉默TREM-2对类风湿关节炎成纤维样滑膜细胞迁移和侵袭的影响

    Institute of Scientific and Technical Information of China (English)

    黄生辉; 李建华; 张玮琼; 刘贵旺; 许锦煌; 郑沛中; 黄建荣

    2016-01-01

    目的:应用RNA干扰(RNAi)技术沉默类风湿关节炎成纤维样滑膜细胞(RA-FLS)髓样细胞触发受体2(TREM-2)的表达,探讨TREM-2基因沉默对RA-FLS迁移和侵袭能力的影响及其相关机制.方法:向RA-FLS转染特异性的TREM-2 siRNA,利用RT-PCR法和Western blot法检测沉默效果;CCK-8法检测各组细胞生长情况;Transwell小室测定细胞的迁移和侵袭能力;ELISA法检测细胞MMP-2和MMP-9的分泌水平;Western blot法分析沉默TREM-2基因对细胞PI3K/AKT通路的影响.结果:TREM-2 siRNA能显著降低RA-FLS中TREM2 mRNA和蛋白的表达(P<0.05).沉默TREM-2基因后,各时点各组细胞的活力未见明显差异;特异性干扰组RA-FLS的迁移细胞数目与空白组和control siRNA组相比明显增多(P <0.05);TREM-2 siRNA组侵袭细胞数目相比空白组和control siRNA组明显增多(P<0.05);TREM-2 siRNA干扰后RA-FLS分泌的MMP-2显著增加(P<0.05)而MMP-9未见明显变化;特异性转染后的RA-FLS相对于对照组PI3 K/AKT的磷酸化水平显著增强(P<0.05).结论:TREM-2可能通过调节PI3 K/AKT通路的活化对RA-FLS的迁移和侵袭能力发挥着重要作用.

  14. 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

  15. Effects of linear polarized infrared light irradiation on the transcriptional regulation of IL-8 expression in IL-1beta-stimulated human rheumatoid synoviocytes involves phosphorylation of the NF-kappaB RelA subunit.

    Science.gov (United States)

    Shibata, Yasuko; Araki, Hidefumi; Oshitani, Toshiyuki; Imaoka, Asayo; Matsui, Masaru; Miyazawa, Keiji; Abiko, Yoshimitsu

    2009-03-03

    Although recent clinical studies have shown that laser therapy acts as an anti-inflammatory effector in the treatment of some diseases, little is known about the mechanism by which it acts in rheumatoid arthritis (RA) patients. The purpose of our work was to examine how irradiation with linear polarized infrared light (LPIL) suppresses inflammatory responses in the MH7A rheumatoid fibroblast-like synoviocyte cell line. We initially confirmed the effects of two disease-modifying anti-rheumatic treatments, LPIL irradiation and dexamethasone (Dex) administration, under experimental inflammatory conditions using gene chip technology. We found that LPIL exerted a smaller effect on gene transcription than Dex; however, IL-1beta-inducible target genes such as the CXCL type chemokines IL-8, IL-1beta and IL-6 were all clearly suppressed by LPIL to the same degree as by Dex. We also found that IL-1beta-induced release of IL-8 from MH7A cells was completely blocked by pretreatment with the (IL-8) inhibitor Bay11-7085, indicating that activation of NF-kappaB signaling plays an important role in the secretion of IL-8. Although the levels of NFKB1 and RELA transcription were unaffected by IL-1beta stimulation, phosphorylation of RelA S276 was suppressed by both LPIL and Dex. Thus LPIL likely exerts its anti-inflammatory effects by inhibiting the release of the inflammatory chemokine IL-8. A fuller understanding of the anti-inflammatory mechanism of LPIL in rheumatoid synoviocytes could serve as the basis for improved treatment of RA patients in the future.

  16. [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

  17. Imatinib mesylate induces mitochondria-dependent apoptosis and inhibits invasion of human pigmented villonodular synovitis fibroblast-like synovial cells.

    Science.gov (United States)

    Chen, Kang; Ren, Qiao; Han, Xiao-Rui; Zhang, Xiao-Nan; Wei, Bo; Bai, Xi-Zhuang

    2016-01-01

    Pigmented villonodular synovitis (PVNS) is a rare sarcoma-like disorder characterized by synovial lesions proliferation and invasion to articular cartilage for which no effective treatments are available. Imatinib mesylate (IM) is known to exert antitumor activity in some tumors, but its effects on PVNS fibroblast-like synoviocytes (PVNS-FLS) and the specific mechanism involved remain to be established. In the present study, the in vitro effects of IM on cell proliferation and survival rates were investigated in PVNS-FLS. Apoptosis induction was assessed via acridine orange/ethidium bromide (AO)/(EB) and Annexin V/PI staining as well as western blotting. The invasion ability of PVNS-FLS was evaluated by Transwell invasion chambers. IM significantly inhibited survival and invasion ability of PVNS-FLS in a dose- and time-dependent manner. The drug-treated cell groups exhibited markedly higher apoptosis, which was blocked upon pretreatment with the specific caspase-9 inhibitor Z-LEHD-FMK. Expression of cleaved caspase-9 was significantly increased and the Bcl-2 family and caspase-3 were activated following treatment with IM. Our results collectively demonstrated that IM has a strong antiproliferative effect on PVNS-FLS in vitro, attributable to induction of mitochondrial-dependent apoptosis in association with activation of caspase-9/-3 and the Bcl-2/Bax family, and exhibits significant inhibition on the invasion ability of PVNS-FLS, suggesting that IM may be useful as a novel treatment of this disease.

  18. 雷公藤甲素诱导胶原导致的关节炎大鼠滑膜细胞凋亡的研究%Triptolide induces apoptosis of rat synoviocytes in collagen- induced arthritis

    Institute of Scientific and Technical Information of China (English)

    涂胜豪; 胡永红; 翁庚民; 陆付耳; 张明敏; 赖先阳; 刘沛霖

    2006-01-01

    目的:以胶原诱导的关节炎(CIA)为动物模型,探讨雷公藤甲素能否诱导CIA大鼠滑膜细胞凋亡.方法:选用雄性Wistar大鼠造模,将造模成功的大鼠随机分为模型组和雷公藤甲素组.雷公藤甲素按40μg/kg BW,肌注给药,每3 d 1次.凋亡检测:给药31 d后处死,取膝关节滑膜,作苏木素-伊红染色(HE)、电镜、缺口末端标记法(TUNEL)标记及流式细胞仪检测.结果:电镜下可见早期阶段的滑膜凋亡细胞.流式细胞仪检测结果显示:正常组、模型组、雷公藤甲素组的凋亡细胞分别为(0.87±0.24)%、(1.83±0.82)%和(3.98±1.16)%.正常组、模型组、雷公藤甲素组的S期细胞分别为(3.4±0.7)%、(8.0±1.4)%和(3.3±1.2)%.雷公藤甲素组与模型组比较差异均显著(P<0.01).TUNEL标记结果显示:正常组、模型组、雷公藤甲素组的凋亡细胞分别为(1.0±0.4)%、(2.2±1.0)%和(4.5±0.9)%,雷公藤甲素组与模型组的差异显著(P<0.01).结论:本实验首次阐明了雷公藤甲素可诱导CIA大鼠滑膜细胞的凋亡.%AIM: To determine whether triptolide induce apoptosis of synovial cells in collagen - induced arthritis(CIA) in rats. METHODS: The male Wistar rats were used to make CIA models by immunized with Bovine collagen Ⅱ ( BC Ⅱ )in Freund's complete adjuvant (FCA). A total of 20 CIA rats were randomly divided into 2 groups, triptolide group (10 rats) and CIA control group (10 rats). Triptolide group were administered with triptolide at 40 μg/kg body weight intramuscularly every three days. CIA control group andanother 10 age - matched normal rats were given normal saline instead. The rats were sacrificed on the 31st day after the triptolide administration. The pieces of synovium of the rat knee joints were harvested. The synovium was examined by HE staining and electron microscope. The apoptosis was tested by TUNEL and flow cytometer. RESULTS: The earlier phase of apoptotic synoviocytes were observed under the electron

  19. Heat and hyposmotic stimulation increase in [Ca2+]i by Ca2+ influx in rat synoviocytes

    Institute of Scientific and Technical Information of China (English)

    SUN WenWu; HU Fen; YANG WenXiu

    2008-01-01

    Rheumatoid arthritis (RA), which is marked by inflammatory synovitis, is a common, chronic autoimmune-disease, whose pathogenesis is complex and still unclear. In order to explore the effects of heat and hyposmotic stimuli on synoviocytes in rheumatoid arthritis, the changes of [Ca2+]i induced by heat, hyposmotic and 4α-PDD stimuli were observed in synoviocytes. [Ca2+]i elevation induced by heat ≥ 28℃, hyposmotic and 4α-PDD stimuli is found to be positively relative to increasing temperature, decreasing osmolality and rising concentration of 4α-PDD. Results show that there is reciprocity among these stimuli and desensitization, and that [Ca2+]i elevation depends on Ca2+ influx, but not necessarily links to Ca2+ release from intracellular stores and voltage-dependent Ca2+ channel in synoviocytes. The above characteristics of Ca2+ influx are similar to those of TRPV4. A probable mechanism has been suggested that heat and hyposmotic stimulation might increase the level of [Ca2+]i by activating the TRPV4-like channel and Ca2+ influx in the synoviocytes.

  20. 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.

  1. COX-2 mRNA expression at different stages of osteoarthritis synoviocytes%不同分期骨关节炎滑膜细胞中COX-2 mRNA表达的差异

    Institute of Scientific and Technical Information of China (English)

    曾明珠; 段戡; 袁长深; 梅其杰; 秦凯

    2014-01-01

    BACKGROUND:COX-2 gene actual y exists in the joint fibroblast-like synoviocytes, it affects osteoarthritis occurrence and development. Understanding the differences of COX-2 gene expression levels at different stages of osteoarthritis synoviocytes has important theoretical significance for the occurrence and development of osteoarthritis, as wel as the role of synoviocytes in this process. OBJECTIVE:To analyze the difference of COX-2 mRNA at different stages of osteoarthritis fibroblast-like synoviocytes. METHODS:Synovial membrane from 44 osteoarthritis patients and 12 normal cases were selected. Primary cells were cultured to passage 4 fibroblast-like synoviocytes for the use in the experiment. COX-2 mRNA expression in osteoarthritis fibroblast-like synoviocytes and normal fibroblast-like synoviocytes was detected using real-time fluorescence quantitative RT-PCR. The relative quantitative analysis was performed using 2-ΔΔCt method. RESULTS AND CONCLUSION:Expression of COX-2 mRNA in osteoarthritis fibroblast-like synoviocytes was significantly higher than that in normal fibroblast-like synoviocytes (P0.05). COX-2 mRNA might be important biological marker for the inflammation in osteoarthritis, and mainly plays a role in early osteoarthritis stage.%背景:COX-2基因实际存在于关节成纤维样滑膜细胞里,影响骨关节炎症的发生、发展。阐明不同分期骨关节炎滑膜细胞中COX-2基因表达量的差异对进一步深入了解骨关节炎的发生与发展,以及滑膜细胞在这一过程中的作用,具有重要的理论意义。  目的:分析COX-2 mRNA在不同分期骨关节炎成纤维样滑膜细胞中表达的差异。  方法:收集膝骨关节炎病变滑膜44例及正常滑膜12例,经原代细胞培养生长至4代的成纤维样滑膜细胞用于实验,应用实时荧光定量RT-PCR检测骨关节炎和正常成纤维样滑膜细胞中COX-2 mRNA的表达情况,最后使用2-ΔΔCt方法进行相对

  2. Renal fibroblast-like cells in Goodpasture syndrome rats.

    Science.gov (United States)

    Okada, H; Inoue, T; Kanno, Y; Kobayashi, T; Ban, S; Kalluri, R; Suzuki, H

    2001-08-01

    The extent of renal fibrosis is the best predictor for functional outcomes in a variety of progressive renal diseases. Interstitial fibroblast-like cells (FbLCs) are presumably involved in the fibrotic process. However, such FbLCs have never been well characterized in the kidney. We characterized renal FbLCs in the nephritic kidney (in which the number of FbLCs and extracellular matrix accumulation were significantly increased) with regards to their expression of phenotypic and functional markers using day 49 Goodpasture syndrome (GPS) rats. Within the renal cortical interstitium, there were a number of alpha-smooth muscle actin(+) (alpha-SMA(+)) FbLCs, negative for vimentin (VIM) and transforming growth factor-beta 1, and not equipped with well-developed rough endoplasmic reticulum and actin-stress fibers. All of these findings were incompatible with the typical features of granulation tissue alpha-SMA(+) myofibroblasts. On the other hand, FbLCs negative for alpha-SMA and VIM produced alpha1(I) procollagen in the nephritic kidney. A number of FbLC populations reside within the cortical interstitium of the kidney in GPS rats, each of which is likely to have developed independently in response to the local conditions of the nephritic kidney, contributing to renal fibrogenesis. Further studies are needed to clarify the key type of FbLC that orchestrates other members to produce renal fibrosis.

  3. Shikonin inhibits TNF-α production through suppressing PKC-NF-κB-dependent decrease of IL-10 in rheumatoid arthritis-like cell model.

    Science.gov (United States)

    Sun, Wen-Xiao; Liu, Yan; Zhou, Wei; Li, He-Wei; Yang, Jian; Chen, Zhen-Bing

    2017-04-01

    Shikonin, a major effective component in the Chinese herbal medicine Lithospermum erythrorhizon Sieb., exhibits an anti-inflammatory property towards rheumatoid arthritis (RA), but the potential mechanism is unclear. Our aim was to investigate the mechanism of shikonin on the lipopolysaccharide (LPS)-induced fibroblast-like synoviocyte (LiFLS) inflammation model. Fibroblast-like synoviocytes (FLSs) were treated with 200 μg/ml of LPS for 24 h to establish the RA-like model, LiFLS. FLSs were pretreated with shikonin (0.1-1 μM) for 30 min in the treatment groups. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect mRNA and protein levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α. Signal proteins involved in IL-10 production were analyzed by Western blotting. Shikonin significantly reversed the inhibitory effects of LPS on IL-10 expression in FLSs by inactivating the PKC-NF-κB pathway. In addition, shikonin inhibited LPS-induced TNF-α expression in FLSs, and this effect was markedly diminished by IL-10-neutralizing antibody. The IL-10-mediated suppression of TNF-α transcription was demonstrated by no response to the protein synthesis inhibitor cyclohexamide and no mRNA decay. Shikonin inhibits LPS-induced TNF-α production in FLSs through suppressing the PKC-NF-κB-dependent decrease in IL-10, and this study also highlights the potential application of shikonin in the treatment of RA.

  4. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol

    Science.gov (United States)

    Zhang, Junqiang; Song, Xianbin; Cao, Wei; Lu, Jinseng; Wang, Xiaoqing; Wang, Gaoyuan; Wang, Zhicheng; Chen, Xiaoyu

    2016-01-01

    Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis. PMID:27611176

  5. 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.

  6. Blockade of IL-17 alleviated inflammation in rat arthritis and MMP-13 expression.

    Science.gov (United States)

    Shui, X-L; Lin, W; Mao, C-W; Feng, Y-Z; Kong, J-Z; Chen, S-M

    2017-05-01

    Rheumatoid arthritis (RA) is one systemic auto-immune disorder featured as chronic synovitis and can destruct joint cartilage. Fibroblast-like synoviocyte (FLS) secretes various factors affecting chondrocyte matrix and degradation. This study thus investigated the effect of interleukin-17A (IL-17A) on FLS and osteoclast. Type II collagen-induced arthritis (CIA) rats were assigned to CIA model, CIA + IgG1 isotype, and CIA + Anti-Rat IL-17A groups. Tissue volume and arthritis index (AI) evaluated arthritis condition. ELISA and flow cytometry measured IL-17A content and Th17 cell percentage in joint cavity fluid. Matrix metallopeptidase 13 (MMP-13) and collagen type II alpha 1 (COL2A1) expression in synovial tissues were compared. FLS-osteoclast co-culture system was treated with IL-17A + IgG1 Isotype or CIA + Anti-Rat IL-17A. MMP-13 and COL2A1 expression were compared. CIA model rats had significantly higher IL-17A and Th17 cell ratio in joint cavity fluid. Injection of Anti-Rat IL-17A decreased AI and tissue volume in model rats, decreased MMP-13 while increased COL2A1 expression in synovial or cartilage tissues. IL-17A treatment remarkably up-regulated MMP-13 mRNA or protein expression in chondrocytes. Anti-IL-17A weakened effects of IL-17A on FLS or chondrocytes. IL-17A inhibits COL2A1 mRNA and protein expression of chondrocyte in the co-culture system via inducing MMP-13 expression in FLS, thus enhancing collagen degradation and playing a role in RA-related cartilage injury.

  7. A formyl peptide receptor agonist suppresses inflammation and bone damage in arthritis.

    Science.gov (United States)

    Kao, W; Gu, R; Jia, Y; Wei, Xuemin; Fan, H; Harris, J; Zhang, Zhiyi; Quinn, J; Morand, E F; Yang, Y H

    2014-09-01

    Annexin A1 (AnxA1) is an endogenous anti-inflammatory protein and agonist of the formyl peptide receptor 2 (FPR2). However, the potential for therapeutic FPR ligands to modify immune-mediated disease has been little explored. We investigated the effects of a synthetic FPR agonist on joint disease in the K/BxN model of rheumatoid arthritis (RA) and RA fibroblast-like synoviocytes (FLS). Arthritis was induced by injection of K/BxN serum at day 0 and 2 in wild-type (WT) or AnxA1(-/-) mice and clinical and histopathological manifestations measured 8-11 days later. WT mice were given the FPR agonist compound 43 (Cpd43) (6 or 30 mg·kg(-1) i.p.) for 4 days. Effects of AnxA1 and Cpd43 on RANKL-induced osteoclastogenesis were assessed in RAW 264.7 cells and human RA FLS and macrophages. Treatment with Cpd43 before or after the onset of arthritis reduced clinical disease severity and attenuated synovial TNF-α and osteoclast-associated gene expression. Deletion of AnxA1 in mice exacerbated arthritis severity in the K/BxN model. In vitro, Cpd43 suppressed osteoclastogenesis and NFAT activity elicited by RANKL, and inhibited IL-6 secretion by mouse macrophages. In human RA joint-derived FLS and monocyte-derived macrophages, Cpd43 treatment inhibited IL-6 release, while blocking FPR2 or silencing AnxA1 increased this release. The FPR agonist Cpd43 reduced osteoclastogenesis and inflammation in a mouse model of RA and exhibited anti-inflammatory effects in relevant human cells. These data suggest that FPR ligands may represent novel therapeutic agents capable of ameliorating inflammation and bone damage in RA. © 2014 The British Pharmacological Society.

  8. 电针"足三里""三阴交"穴对胶原性关节炎大鼠滑膜细胞分泌功能的影响%Effect of Electroacupuncture at "Zusanli"(ST 36)and "Sanyinjiao"(SP 6)on Collagen-induced Arthritis and Secretory Function of Knee-joint Synoviocytes in Rats

    Institute of Scientific and Technical Information of China (English)

    方剑乔; 邵晓梅; 马桂芝

    2009-01-01

    目的:观察电针"足三里""三阴交"对胶原性关节炎(collagen-induced arthritis,CIA)大鼠的治疗作用,并探讨该疗法调节CIA大鼠滑膜细胞分泌功能的部分机制.方法:36只Wistar大鼠随机分为正常对照组、模型对照组和电针治疗组.模型对照组和电针治疗组采用牛Ⅱ型胶原在大鼠背部正中线作多点皮内注射诱发CIA模型.电针治疗组选取"足三里""三阴交"穴进行电针刺激,频率2 Hz,强度2 mA,时间30 min,连续治疗30 d.处理前后分别观察CIA大鼠足跖肿胀度、痛阈;采用ELISA法检测大鼠膝关节滑膜细胞培养上清液中前列腺素E_2(PGE_2)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)水平.结果:模型对照组大鼠足跖肿胀度,滑膜细胞培养上清中PGE_2浓度和TNF-α、IL-1β含量均高于正常对照组大鼠,差异有统计学意义(P<0.05,P<0.01),痛阈低于正常对照组大鼠,差异有统计学意义(P<0.05).与模型对照组比较,电针治疗组大鼠足跖肿胀度减小,痛阈升高,关节滑膜细胞培养上清中PGE_2浓度下降,TNF-α和IL-1β含量降低,差异有统计学意义(P<0.05).结论:电针"足三里""三阴交"穴对胶原性关节炎大鼠具有良好的治疗作用,该作用可能与抑制关节滑膜细胞的分泌功能有关.%Objective To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on collagen-induced arthritis (CIA) and its underlying mechanism in regulating the secretory function of knee-joint synovial cells in CIA rats. Methods Thirty-six Wistar rats were equally randomized into control, model and EA groups. CIA model (rheumatoid arthritis) was duplicated by intradermal injection of Bovine type E collagen into the back of the anesthetized rats. EA (2 Hz, 2 mA) was applied to "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 30 min, once a day for 30 days. The paw volume was measured by using a Plethysmometer and hot water tail-flick tests (50

  9. Regulation of lubricin/superficial zone protein by Wnt signalling in bovine synoviocytes.

    Science.gov (United States)

    Inui, Atsuyuki; Iwakura, Takashi; Hari Reddi, A

    2016-02-01

    Lubricin, homologous to superficial zone protein (SZP), functions as a boundary lubricant in articular cartilage and plays an essential role in the maintenance of joint function and homeostasis. Wnt signalling plays a key role in joint development, including synovial joint formation, and several Wnt proteins are expressed in the synovium and articular cartilage in arthritis. The aim of this study was to determine the role of Wnt signalling on SZP accumulation in synoviocytes. Isolated synoviocytes from bovine knee joints were cultured with Wnt proteins (Wnt-3a and Wnt-5a) and antagonists or agonists of the Wnt-β-catenin pathway or Wnt-Ca(2+) pathway in serum-free chemically defined medium. SZP accumulation in the culture medium was determined by enzyme-linked immunosorbent assay. Wnt-3a suppressed SZP accumulation via a Wnt-β-catenin-dependent pathway. In contrast, Wnt-5a stimulated SZP accumulation via a β-catenin independent pathway. The present investigation provides novel insights into the role of the Wnt signalling pathways in SZP accumulation in synoviocytes and their roles in the homeostasis of normal joints.

  10. 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.

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

    Science.gov (United States)

    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.

  12. Integrative omics analysis of rheumatoid arthritis identifies non-obvious therapeutic targets.

    Directory of Open Access Journals (Sweden)

    John W Whitaker

    Full Text Available Identifying novel therapeutic targets for the treatment of disease is challenging. To this end, we developed a genome-wide approach of candidate gene prioritization. We independently collocated sets of genes that were implicated in rheumatoid arthritis (RA pathogenicity through three genome-wide assays: (i genome-wide association studies (GWAS, (ii differentially expression in RA fibroblast-like synoviocytes (FLS, and (iii differentially methylation in RA FLS. Integrated analysis of these complementary data sets identified a significant enrichment of multi-evidence genes (MEGs within pathways relating to RA pathogenicity. One MEG is Engulfment and Cell Motility Protein-1 (ELMO1, a gene not previously considered as a therapeutic target in RA FLS. We demonstrated in RA FLS that ELMO1 is: (i expressed, (ii promotes cell migration and invasion, and (iii regulates Rac1 activity. Thus, we created links between ELMO1 and RA pathogenicity, which in turn validates ELMO1 as a potential RA therapeutic target. This study illustrated the power of MEG-based approaches for therapeutic target identification.

  13. Reduction of IL-20 Expression in Rheumatoid Arthritis by Linear Polarized Infrared Light Irradiation.

    Science.gov (United States)

    Imaoka, Asayo; Zhang, Lin; Kuboyama, Noboru; Abiko, Yoshimitsu

    2014-07-01

    Low-level laser is being evaluated for treating rheumatoid arthritis (RA). Recently, the linear polarized infrared light (Super Lizer, SL) irradiation may also be useful for RA treatment. However, the molecular mechanism underlying the effectiveness of SL on RA is unclear. It has been IL-20 may involved in RA disease progression. To understand how SL action, we constructed the experimental model in vitro using human rheumatoid fibroblast-like synoviocyte (MH7A) and collagen induced (CIA) RA rat in vivo. We examined the effect of SL irradiation on IL-20 gene expression in MH7A and IL-20 protein production in CIA) rat joints. MH7A was cultured and challenged with IL-1ß, then examined IL-20 and IL-20R mRNA level by DNA microarray. IL-20 protein expression was examined by immunohistochemistry using a specific antibody against rat IL-20. Scatter plot analysis demonstrated that an increase in IL-20 gene expression by IL-1ß was reduced by SL irradiation, but IL-20R did not show a significant change. The Immunohistochemical analysis demonstrated a strong IL-20 staining in synovial membrane tissue of CIA rat joint, and SL irradiation significantly reduced the staining. Since IL-20 has been identified as an important cytokine in the pathogenesis of RA, the reduction of IL-20 expression by SL irradiation may be one of mechanisms in reduction of inflammation in RA joints by SL irradiation suggesting that SL irradiation may be useful for RA therapy.

  14. Hypoxia-inducible factor-2α is an essential catabolic regulator of inflammatory rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Je-Hwang Ryu

    2014-06-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune disorder that manifests as chronic inflammation and joint tissue destruction. However, the etiology and pathogenesis of RA have not been fully elucidated. Here, we explored the role of the hypoxia-inducible factors (HIFs, HIF-1α (encoded by HIF1A and HIF-2α (encoded by EPAS1. HIF-2α was markedly up-regulated in the intimal lining of RA synovium, whereas HIF-1α was detected in a few cells in the sublining and deep layer of RA synovium. Overexpression of HIF-2α in joint tissues caused an RA-like phenotype, whereas HIF-1α did not affect joint architecture. Moreover, a HIF-2α deficiency in mice blunted the development of experimental RA. HIF-2α was expressed mainly in fibroblast-like synoviocytes (FLS of RA synovium and regulated their proliferation, expression of RANKL (receptor activator of nuclear factor-κB ligand and various catabolic factors, and osteoclastogenic potential. Moreover, HIF-2α-dependent up-regulation of interleukin (IL-6 in FLS stimulated differentiation of TH17 cells-crucial effectors of RA pathogenesis. Additionally, in the absence of IL-6 (Il6-/- mice, overexpression of HIF-2α in joint tissues did not cause an RA phenotype. Thus, our results collectively suggest that HIF-2α plays a pivotal role in the pathogenesis of RA by regulating FLS functions, independent of HIF-1α.

  15. 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.

  16. mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin

    DEFF Research Database (Denmark)

    Andreassen, Stine Mandrup; Berg, Lise Charlotte; Nielsen, Søren Saxmose;

    2015-01-01

    ) and protease activator receptor 1 (PAR-1) was assessed using quantitative real time reverse transcriptase PCR. Results: LPS caused a significant increase in mRNA expression of SAA, IL-6, MCP-1 and uPA, and a decrease in TF, PAI-1 and PAR-1 when compared to non-treated cells. Treatment with thrombin resulted...

  17. Production of serum amyloid A in equine articular chondrocytes and fibroblast-like synoviocytes treated with proinflammatory cytokines and its effects on the two cell types in culture

    DEFF Research Database (Denmark)

    Jacobsen, Stine; Ladefoged, Søren; Berg, Lise Charlotte

    2016-01-01

    -sensitive protein were assessed by quantitative real-time PCR assay; SAA protein was evaluated by immunoturbidimetry and denaturing isoelectric focusing and western blotting. RESULTS: All cytokine stimulation protocols increased expression of SAA mRNA and resulted in detectable SAA protein production...

  18. Allergy and Immunology

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    2011182 Modulation of RhoA/ROCK pathway on TLR-2 ligand-induced chemokine secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. LIANG Liuqin(梁柳琴),et al. Dept Rheumatol,1st Affil Hosp

  19. The effect of gallium nitrate on synoviocyte MMP activity.

    Science.gov (United States)

    Panagakos, F S; Kumar, E; Venescar, C; Guidon, P

    2000-02-01

    Gallium, a group IIIa metal salt, has been demonstrated to be an effective immunosuppressive agent. Gallium has also been shown to inhibit the production of inflammatory cytokines, such as IL-1beta, produced by macrophage-like cells in vitro. To further characterize the effects of gallium on the inflammatory process, we examined the effects of gallium nitrate on matrix metalloproteinase (MMP) activity utilizing the rabbit synoviocyte cell line HIG-82. HIG-82 cells were incubated with IL-1beta and TPA, with and without increasing concentrations of gallium nitrate. Conditioned medium was collected and assayed for MMP activity using a synthetic substrate and substrate gel zymography. IL-1beta and TPA alone induced MMP activity in HIG-82 cells. A dose-dependent inhibition of IL-1beta and TPA stimulated MMP activity by gallium nitrate at increasing concentrations was observed. This study demonstrates that gallium nitrate can inhibit the activity of MMPs and may be useful as a modulator of inflammation in arthritis.

  20. An attempt to eliminate fibroblast-like cells from primary cultures of fetal human livers.

    Directory of Open Access Journals (Sweden)

    Tokiwa,Takayoshi

    1986-04-01

    Full Text Available The elimination of fibroblast-like cells from primary cultures of fetal human livers was studied. A fibroblast-like cell line (HuF, which was obtained by subculturing fetal human liver cells 4 or more times, was briefly treated with hydrocortisone (HC or putrescine (PUT. The growth of HuF cells was inhibited by HC at a concentration of 10(-2 M and by PUT at a concentration higher than 10(-3 M. Long-term treatment of HuF cells with 10(-3 M HC inhibited the growth of the cells. Primary cultures of fetal human livers were made in medium containing HC or PUT, and morphological and functional examinations were made. The cultures were predominantly composed of epithelial-like cells, with few fibroblast-like cells, when the HC concentration was 10(-5M to 10(-3 M. A high amount of albumin was secreted at these concentrations of HC. On the other hand, at 10(-3 M PUT, many epithelial-like cells were seen, but albumin was undetectable. The present results indicate that albumin-producing epithelial-like cells can be selectively maintained in medium containing HC, in primary cultures of fetal human livers.

  1. 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.

  2. Immunocytochemical localization of caveolin-3 in the synoviocytes of the rat temporomandibular joint during development.

    Science.gov (United States)

    Niwano, Masahiro; Nozawa-Inoue, Kayoko; Suzuki, Akiko; Ikeda, Nobuyuki; Takagi, Ritsuo; Maeda, Takeyasu

    2008-03-01

    Caveolins -- caveolin-1, -2, -3 (Cav1, 2, 3) -- are major components of caveolae, which have diverse functions. Our recent study on the temporomandibular joint (TMJ) revealed expressions of Cav1 and muscle-specific Cav3 in some synovial fibroblast-like type B cells with well-developed caveolae. However, the involvement of Cav3 expression in the differentiation and maturation of type B cells remains unclear. The present study therefore examined the chronological alterations in the localization of Cav3 in the synovial lining cells of the rat TMJ during postnatal development by immunocytochemical techniques. Observations showed immature type B cells possessed a few caveolae with Cav1 but lacked Cav3 protein at postnatal day 5 (P5). At P14, Cav3-immunopositive type B cells first appeared in the synovial lining layer. They increased in number and immunointensity from P14 to P21 as occlusion became active. In immunoelectron microscopy and double immunolabeling with heat shock protein 25 (Hsp25) and Cav3, coexpressed type B cells developed rough endoplasmic reticulum and numerous caveolae, while the Cav3-immunonegative type B cell with Hsp25 immunoreaction possessed few of these. Results suggest that Cav3 expression, which is closely related to added functional stimuli, reflects the differentiation of the type B synoviocytes.

  3. 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.

  4. Pathway of PPAR-gamma coactivators in thermogenesis: a pivotal traditional Chinese medicine-associated target for individualized treatment of rheumatoid arthritis.

    Science.gov (United States)

    Zhang, Yanqiong; Mao, Xia; Guo, Qiuyan; Bai, Ming; Zhang, Bo; Liu, Chunfang; Sun, Yanqun; Li, Shao; Lin, Na

    2016-03-29

    Traditional Chinese medicine (TCM) syndromes have been regarded as the crucial clinical manifestations for individualized diagnosis and treatment of complex diseases, including rheumatoid arthritis (RA) and cancer. Especially, RA patients are classified into cold and hot syndromes with different clinical manifestations, interventions and molecular mechanisms. Better effectiveness of a classic cold syndrome-specific herbal formula Wu-tou decoction (WTD) has been achieved. To explore molecular mechanisms of syndrome-specific formulae is of great clinical significance to improve the effectiveness and pertinence of treatment for the complex diseases with personalized conditions. However, the scientific basis of WTD treatment on RA with the cold syndrome remains unclear. Here, we predicted the putative targets for composite compounds contained in WTD using drugCIPHER-CS and constructed a WTD herbs-putative targets-RA related genes network. Next, a list of major WTD targets was identified based on their topological features, including the degree, node betweenness, closeness and k-coreness in the above pharmacological network. Importantly, pathway enrichment analysis revealed that these major WTD targets were significantly associated with the pathway of peroxisome proliferator-activated receptor (PPAR)-gamma (PPAR-γ) coactivators in thermogenesis. These computational findings were subsequently verified by experiments on a rat model of collagen-induced arthritis (CIA) with cold or hot syndromes, and on human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cell line. In conclusion, the pathway of PPAR-γ coactivators in thermogenesis might be one of the potential pharmacological targets of WTD to alleviate RA with the TCM cold syndrome. These findings may open new avenues for designing individualized treatment regimens for RA patients.

  5. Cytotoxic effects of new MTA-based cement formulations on fibroblast-like MDPL-20 cells.

    Science.gov (United States)

    Garcia, Lucas da Fonseca Roberti; Santos, Alailson Domingos dos; Moraes, João Carlos Silos; Costa, Carlos Alberto de Souza

    2016-01-01

    The present study aimed at evaluating the cytotoxic effects of a novel cement called CER on periodontal fibroblast-like cells of mice (MDPL-20), in comparison with different formulations of Mineral Trioxide Aggregate (MTA), by means of the cell viability test (MTT) and cell morphology analysis. Thirty-two round-shaped samples were fabricated with the following cements: white MTA, white and gray CER and experimental white MTA. The samples were immersed in serum-free culture medium for 24 hours or 7 days (n = 16). The extracts (culture medium + components released from the cements) were applied for 24 hours to previously cultured cells (40.000 cells/cm2) in the wells of 24-well plates. Cells seeded in complete culture medium were used as a negative control. Cell viability was assessed using the MTT assay. Two samples of each cement were used for cell morphology analysis by Scanning Electron Microscopy (SEM). The extracts obtained at the 7-day period presented higher cytotoxicity compared with the 24-hour period (p MTA presented the lowest, similar to the control (p > 0.05). However, at the 7-day period, the experimental white MTA presented no significant difference in comparison with the other cements (p > 0.05). At the 7-day period, CER cement presented cytotoxic effects on fibroblast-like cells, similar to different MTA formulations. However, the immersion period in the culture medium influenced the cytotoxicity of the cements, which was greater for CER cement at 24 hours.

  6. Identification of NURR1 as a mediator of MIF signaling during chronic arthritis: effects on glucocorticoid-induced MKP1.

    Science.gov (United States)

    Ralph, Jennifer A; Ahmed, Afsar U; Santos, Leilani L; Clark, Andrew R; McMorrow, Jason; Murphy, Evelyn P; Morand, Eric F

    2010-11-01

    Elucidation of factors regulating glucocorticoid (GC) sensitivity is required for the development of "steroid-sparing" therapies for chronic inflammatory diseases, including rheumatoid arthritis (RA). Accumulating evidence suggests that macrophage migration inhibitory factor (MIF) counterregulates the GC-induction of anti-inflammatory mediators, including mitogen-activated protein kinase phosphatase 1 (MKP1), a critical mitogen-activated protein kinase signaling inhibitor. This observation has yet to be extended to human disease; the molecular mechanisms remain unknown. We investigated NURR1, a GC-responsive transcription factor overexpressed in RA, as a MIF signaling target. We reveal abrogation by recombinant MIF (rMIF) of GC-induced MKP1 expression in RA fibroblast-like synoviocytes (FLS). rMIF enhanced NURR1 expression, artificial NBRE (orphan receptor DNA-binding site) reporter transactivation, and reversed GC-inhibition of NURR1. NURR1 expression was reduced during experimental arthritis in MIF-/- synovium, and silencing MIF reduced RA FLS NURR1 mRNA. Consistent with NBRE identification on the MKP1 gene, MKP1 mRNA was reduced in FLS that ectopically express NURR1, and silencing NURR1 enhanced MKP1 mRNA in RA FLS. rMIF enhanced NBRE binding on the MKP1 gene, and the absence of the NBRE prevented NURR1-repressive effects on basal and GC-induced MKP1 transactivation. This study defines NURR1 as a novel MIF target in chronic inflammation and demonstrates a role for NURR1 in regulating the anti-inflammatory mediator, MKP1. We propose a MIF-NURR1 signaling axis as a regulator of the GC sensitivity of MKP1.

  7. Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells.

    Directory of Open Access Journals (Sweden)

    Paola Brun

    Full Text Available Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR-γ, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-γ anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and

  8. 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

  9. 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

  10. Ultrastructural observations of fibroblast-like cells forming gap junctions in the W/W(nu) mouse small intestine.

    Science.gov (United States)

    Horiguchi, K; Komuro, T

    2000-05-12

    The ultrastructure of the wild-type (+/+) mice small intestine was compared with c-kit mutant (W/W(nu)) mice which only have few interstitial cells of Cajal (ICC) associated with Auerbach's plexus, in order to elucidate whether the specialized membrane contacts are general features of so-called fibroblast-like cells that are widely distributed in the tunica muscularis of the alimentary tract. Fibroblast-like cells in the Auerbach region were found in approximately equal number in W/W(nu) mice as in +/+ mice, while ICC associated with Auerbach's plexus (ICC-AP) could not be demonstrated in W/W(nu) mice in the present investigation. Fibroblast-like cells were characterized by cytoplasm of moderate to high electron density, well developed rough endoplasmic reticulum and nuclei with thick peripheral accumulations of heterochromatin. There were no basal lamina and caveolae along the cell membrane. It was observed that single fibroblast-like cells formed probable small gap junctions with muscle cells of both circular and longitudinal layers. Fibroblast-like cells with the same features were also observed in the region of the deep muscular plexus in both +/+ and W/W(nu) mice. The present observation, together with our previous studies on rats and guinea-pigs, suggest the common presence of gap junctions or gap junction-like structures on fibroblast-like cells in the gastrointestinal musculature and their involvement in the regulatory system of gastrointestinal motility by passing electrical or molecular signals to influence the state of muscle tonus.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

  13. Characterization of a novel fibroblast-like cell line from rainbow trout and responses to sublethal anoxia

    DEFF Research Database (Denmark)

    Ossum, Carlo Gunnar; Hoffmann, Else Kay; Vijayan, M.M.;

    2004-01-01

    A novel fibroblast-like cell line RTHDF was established from hypodermal connective tissue of rainbow trout Oncorhynchus mykiss and telomerase activity was demonstrated early and late in cell line development. When RTHDF cells were exposed to bioenergetic stress, i.e. anoxia, activation...... suggests that RTHDF can be useful in studying biochemical responses of teleost cells to environmental stress....

  14. Baicalin Inhibits IL-17-Mediated Joint Inflammation in Murine Adjuvant-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    Xue Yang

    2013-01-01

    Full Text Available T-helper-17 (Th17 cells are implicated in a number of inflammatory disorders including rheumatoid arthritis. Antagonism of Th17 cells is a treatment option for arthritis. Here, we report that Baicalin, a compound isolated from the Chinese herb Huangqin (Scutellaria baicalensis Georgi, relieved ankle swelling and protected the joint against inflammatory destruction in a murine adjuvant-induced arthritis model. Baicalin inhibited splenic Th17 cell population expansion in vivo. Baicalin prevented interleukin- (IL- 17-mediated lymphocyte adhesion to cultured synoviocytes. Baicalin also blocked IL-17-induced intercellular adhesion molecule 1, vascular cell adhesion molecule 1, IL-6, and tumor necrosis factor-alpha mRNA expression in cultured synoviocytes. Collectively, these findings suggest that Baicalin downregulates the joint inflammation caused by IL-17, which is likely produced by an expanded population of splenic Th17 cells in experimental arthritis. Baicalin might be a promising novel therapeutic agent for treating rheumatoid arthritis in humans.

  15. Comparative analysis of the expression of surface markers on fibroblasts and fibroblast-like cells isolated from different human tissues.

    Science.gov (United States)

    Lupatov, A Yu; Vdovin, A S; Vakhrushev, I V; Poltavtseva, R A; Yarygin, K N

    2015-02-01

    Expression of 20 surface markers was analyzed in cultures of mesenchymal stromal cells of the umbilical cord, fibroblasts from adult and fetal human skin, and fibroblast-like cells of fetal liver was analyzed by fl ow cytometry. The studied cultures did not express hemopoietic cells markers, but were positive for CD73, CD90, and CD105 markers recommended by the International Society of Cell Therapy for the identification of the multipotent mesenchymal stromal cells. Fetal liver fibroblast-like cells were positive for CD54; this marker was absent in skin fibroblast cultures, but was expressed by umbilical cord mesenchymal stromal cells. Further study of these cells revealed a minor subpopulation of cells co-expressing CD24 and CD90 or CD24 and CD54. We hypothesized that these cells probably participate in epithelial mesenchymal transition.

  16. 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.

  17. Effect of 660 nm Light-Emitting Diode on the Wound Healing in Fibroblast-Like Cell Lines

    Directory of Open Access Journals (Sweden)

    Myung-Sun Kim

    2015-01-01

    Full Text Available Light in the red to near-infrared (NIR range (630–1000 nm, which is generated using low energy laser or light-emitting diode (LED arrays, was reported to have a range of beneficial biological effects in many injury models. NIR via a LED is a well-accepted therapeutic tool for the treatment of infected, ischemic, and hypoxic wounds as well as other soft tissue injuries in humans and animals. This study examined the effects of exposure to 660 nm red LED light at intensities of 2.5, 5.5, and 8.5 mW/cm2 for 5, 10, and 20 min on wound healing and proliferation in fibroblast-like cells, such as L929 mouse fibroblasts and human gingival fibroblasts (HGF-1. A photo illumination-cell culture system was designed to evaluate the cell proliferation and wound healing of fibroblast-like cells exposed to 600 nm LED light. The cell proliferation was evaluated by MTT assay, and a scratched wound assay was performed to assess the rate of migrating cells and the healing effect. Exposure to the 660 nm red LED resulted in an increase in cell proliferation and migration compared to the control, indicating its potential use as a phototherapeutic agent.

  18. The suppressive effects of Saposhnikovia divaricata (Fangfeng) chromone extract on rheumatoid arthritis via inhibition of nuclear factor-κB and mitogen activated proteinkinases activation on collagen-induced arthritis model.

    Science.gov (United States)

    Kong, Xiangying; Liu, Chunfang; Zhang, Cun; Zhao, Juan; Wang, Jianzhu; Wan, Hongye; Zhu, Hongwei; Zhang, Ping; Chen, Weiheng; Xiao, Yongqing; Lin, Na

    2013-07-30

    Saposhnikovia divaricata (SD), called "Fangfeng" in China, is commonly used in clinical compound prescription for treatment of rheumatoid arthritis (RA), but its actions on RA have not been clarified. The present study aims to determine the anti-inflammatory activity of SD chromone extract (SCE), the major bioactive component of SD, on collagen-induced arthritis (CIA) rats, and elucidate its underlying mechanisms with regards to its molecular basis of action on human fibroblast-like synoviocytes derived from RA patients (HFLS-RA). CIA model on rats was constructed by injection of bovine type II collagen. Rats were pre-treated with different dosages of SCE from 3 days before till 35 days after model building. The progression of CIA was evaluated by macroscopic scoring, X-ray observation and hematoxylin and eosin (HE) staining of paws. HFLS-RA were pre-treated with different concentrations of SCE prior to stimulation with 10 ng/ml of tumor necrosis factor (TNF) α. By radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), levels of interleukin (IL)-1β, IL-6, TNFα and prostaglandin E2 (PGE2) were quantified respectively. Nuclear factor (NF-κB) p65 expression and DNA-binding activity were tested by immunohistochemisty and electrophoretic mobility shift assay (EMSA) respectively. Phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPKs were examined by immunohistochemisty staining and western blot analysis. Histological examination and radiological observation demonstrated that SCE significantly reduced the inflammatory responses in the joints of CIA rats. SCE inhibited the production of TNFα, IL-1β, and IL-6 in the joint tissues and sera. The level of PGE2 in sera was also decreased by SCE. Moreover, SCE treatment in vivo was able to reduce protein level of NF-κB, the transcriptional factor closely related to the inflammatory process, in articular synovium and cartilage of CIA rats. In addition, SCE

  19. Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast-like cell type that overexpresses Ptch.

    Science.gov (United States)

    Dicker, Anthony J; Serewko, Magdalena M; Russell, Terry; Rothnagel, Joseph A; Strutton, Geoff M; Dahler, Alison L; Saunders, Nicholas A

    2002-05-01

    In this study we report on the isolation and characterization of a nonepithelial, nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a patient. The BCC1 cells share many characteristics with dermal fibroblasts, such as the expression of vimentin, lack of expression of cytokeratins, and insensitivity to agents that cause growth inhibition and differentiation of epithelial cells; however, significant differences between BCC1 cells and fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA synthesis in response to interferon-gamma, whereas dermal fibroblasts are not. More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch and ptch2. These data indicate that basal cell carcinomas are associated with a functionally distinct population of fibroblast-like cells that overexpress known tumor-specific markers (ptch and ptch2).

  20. Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis.

    Science.gov (United States)

    Bonaventura, Paola; Courbon, Guillaume; Lamboux, Aline; Lavocat, Fabien; Marotte, Hubert; Albarède, Francis; Miossec, Pierre

    2017-05-25

    Synovium hyperplasia characterizes joint diseases, such as rheumatoid arthritis (RA). The cytotoxic effect of low-dose Cadmium (Cd) was tested in vitro and ex vivo on synoviocytes, the mesenchymal key effector cells of inflammation and proliferation in arthritis. The anti-inflammatory and anti-proliferative effects of Cd were tested in vivo by intra-articular injection in the adjuvant induced arthritis rat joints, where the clinical scores and the consequences of arthritis were evaluated. Cell death through apoptosis was highly induced by Cd in inflammatory synoviocytes (80% reduction of cell viability, p < 0.01). TNF plus IL-17 cytokine combination induced a two-fold increase of Cd cell content by enhancing the ZIP-8 importer and the MT-1 homeostasis regulator expression. Addition of Cd reduced IL-6 production in TNF plus IL-17-activated synoviocytes (up to 83%, p < 0.05) and in ex-vivo synovium biopsies (up to 94%, p < 0.01). Cd-injection in rat joints improved arthritis, reducing clinical scores (arthritic score reduced from 4 to 2, p < 0.01), inflammatory cell recruitment (up to 50%, p < 0.01) and protecting from bone/cartilage destruction. This proof of concept study is supported by the limited Cd spread in body reservoirs, with low-dose Cd providing a safe risk/benefit ratio, without toxic effects on other cell types and organs.

  1. 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. ...

  2. Enhancement of terminal B lymphocyte differentiation in vitro by fibroblast-like stromal cells from human spleen.

    Science.gov (United States)

    Skibinski, G; Skibinska, A; Stewart, G D; James, K

    1998-12-01

    Stromal elements are major components of lymphoid tissues contributing to both tissue architecture and function. In this study we report on the phenotype and function of fibroblast-like stromal cells obtained from human spleen. These cells express high levels of CD44 and ICAM-1 and moderate levels of VLA-4, VCAM, CD40 and CD21. They fail to express endothelial, epithelial, lymphocyte and monocyte/macrophage markers. We show that these cells interact with B cell blasts induced in vitro by anti-CD40 and anti-mu stimulation. As a result of these interactions both IL-6 and IgG secretion into culture medium is increased. The enhanced secretion of IgG is partly inhibited by abolishing B cell blaststromal cell contact or by anti-IL-6, anti-VCAM or anti-CD49d antibodies. Our studies also suggest that the ability of stromal cells to promote B cell survival is most likely the underlying mechanism of the enhanced immunoglobulin secretion. Comparison of stromal cells from different lymphoid and non-lymphoid organs revealed that bone marrow- and spleen-derived stromal cells are the most effective in promoting B cell blast differentiation.

  3. Recovery of fibroblast-like cells from refrigerated goat skin up to 41 d of animal death.

    Science.gov (United States)

    Okonkwo, Charles; Singh, Mahipal

    2015-05-01

    Successful cloning of animals using somatic cell nuclear transfer requires undamaged nuclear DNA from desired donor cell types. In vitro culture of cells is one way of ensuring nuclear integrity. The goal of this study was to evaluate the limits of postmortem cell survival/culture in refrigerated goat ear skin tissues which could be used for long-term storage and cloning of animals in future. To achieve this, 60 explants from 6 different goats were cultured after 0, 3, 6, 9, 13, 16, 20, 23, 27, 30, 33, 37, and 41 d postmortem and observed under inverted microscope for outgrowth of fibroblast-like cells, after 10-12 d of culture. Explants from all time points including 19% from 41-dpm tissues exhibited outgrowth. However, the percentage of outgrowth positive explants, as well as culture confluence, reduced with increasing postmortem time interval. Cell cultures established from primary outgrowth of 41-dpm tissues when compared for their growth profile with similarly obtained 0-dpm cultures revealed similar growth curve and cell morphology. Cytogenetic analysis of 41-dpm tissue-derived cell populations revealed a normal female karyotype with 60 XX homologous chromosomes indicating genetic stability of the cell population. In conclusion, these results show that refrigerated skin tissue remains alive for more than a month and that the cells derived from such tissues are normal and can be cryopreserved for long-term storage and future cloning of animals with desired genetics.

  4. Proliferation of mouse fibroblast-like and osteoblast-like cells on pure titanium films manufactured by electron beam melting.

    Science.gov (United States)

    Kawase, Mayu; Hayashi, Tatsuhide; Asakura, Masaki; Tomino, Masafumi; Mieki, Akimichi; Kawai, Tatsushi

    2016-10-01

    The physical characteristics and biological compatibility of surfaces produced by electron beam melting (EBM) are not well known. In particular, there are not many reports on biocompatibility qualities. In this study, pure Ti films were manufactured using EBM. While it is reported that moderately hydrophilic biomaterial surfaces display improved cell growth and biocompatibility, contact angle measurements on the EBM-produced pure Ti films showed slight hydrophobicity. Nonetheless, we found the cell count of both fibroblast-like cells (L929) and osteoblast-like cells (MC3T3-E1) increased on pure Ti films, especially the MC3T3-E1, which increased more than that of the control. In addition, the morphology of L929 and MC3T3-E1 was polygonal and spindle-shaped and the cytoskeleton was well developed in the pure Ti surface groups. Upon staining with Alizarin red S, a slight calcium deposition was observed and this level gradually rose to a remarkable level. These results indicate that pure Ti films manufactured by EBM have good biocompatibility and could be widely applied as biomedical materials in the near future. © 2016 International Federation for Cell Biology.

  5. 青蒿琥酯对类风湿关节炎患者滑膜细胞凋亡及细胞因子水平的影响%Effect of artesunate on apoptosis and CCL5 production of synoviocytes of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    李燕; 何蓉; 巫婷婷; 刘江南

    2015-01-01

    Objective This study is aimed to delemine the inhibitory effects onCCL5 cytokine production and promoting early stage apoptosis of Artesunate(ART) in the fibroblast-likesynoviocytes (FLS) from patients with rheumatoid arthritis(RA).Methods:(1) FLS were incubated with different concentration ART for 24h, and were incubated with 12.5µg /ml ART for different time,Flow cytometry was applied to detect the apoptosis of FLS. (2) FLS were incubated with different concentration ART and MTX for 48h.,ELISA was applied to detect the levels of CCL5 in the cell culturation clear supernatant.Results(1) Different concentration ART were found to promot apoptosis on FLS compared with the controlled group (P<0.05), and ART appeared to be in a dosage and time dependent manner; (2) Different concentration ART and MTX presented remarkable inhibitory action on the levels of CCL5 compared with the controlled group (P<0.05), and ART appeared to be in a dosage dependent manner at the concentration ranging from 3.125-50µg /ml.ConclusionThe effect of ART were remarkable on patients with rheumatoid arthritis. The mechanism of action may be realized through inhibiting FLS CCL5 cytokine and advancing FLS apoptosis.%目的:观察不同浓度的青蒿琥酯(ART)对人类风湿关节炎(Rheumatoid arthritis,RA)滑膜细胞凋亡和细胞因子CCL5水平的影响,探讨青蒿琥酯治疗RA的免疫机制。方法:收集RA患者关节液标本25例,体外分离培养滑膜细胞,以生长良好的3~5代滑膜细胞进行实验,调整细胞浓度,分为细胞对照组、ART组、MTX组。(1)不同浓度的 ART作用于滑膜细胞24h,12.5µg/ml ART作用滑膜细胞8、24、48h,用流式细胞术分别检测其细胞凋亡。(2)不同浓度ART 和MTX分别处理滑膜细胞48h,用ELISA法检测其细胞培养上清液中 CCL5水平。结果:(1)对 RA滑膜细胞凋亡的影响:ART在3.125~25µg /ml浓度范围内作用滑膜细胞24h后,早期凋

  6. Relationship between interstitial cells of Cajal, fibroblast-like cells and inhibitory motor nerves in the internal anal sphincter.

    Science.gov (United States)

    Cobine, Caroline A; Hennig, Grant W; Kurahashi, Masaaki; Sanders, Kenton M; Ward, Sean M; Keef, Kathleen D

    2011-04-01

    Interstitial cells of Cajal (ICC) have been shown to participate in nitrergic neurotransmission in various regions of the gastrointestinal (GI) tract. Recently, fibroblast-like cells, which are positive for platelet-derived growth factor receptor α (PDGFRα(+)), have been suggested to participate additionally in inhibitory neurotransmission in the GI tract. The distribution of ICC and PDGFRα(+) cell populations and their relationship to inhibitory nerves within the mouse internal anal sphincter (IAS) are unknown. Immunohistochemical techniques and confocal microscopy were therefore used to examine the density and arrangement of ICC, PDGFRα(+) cells and neuronal nitric-oxide-synthase-positive (nNOS(+)) nerve fibers in the IAS of wild-type (WT) and W/W ( v ) mice. Of the total tissue volume within the IAS circular muscle layer, 18% consisted in highly branched PDGFRα(+) cells (PDGFRα(+)-IM). Other populations of PDGFRα(+) cells were observed within the submucosa and along the serosal and myenteric surfaces. Spindle-shaped intramuscular ICC (ICC-IM) were present in the WT mouse IAS but were largely absent from the W/W ( v ) IAS. The ICC-IM volume (5% of tissue volume) in the WT mouse IAS was significantly smaller than that of PDGFRα(+)-IM. Stellate-shaped submucosal ICC (ICC-SM) were observed in the WT and W/W ( v ) IAS. Minimum surface distance analysis revealed that nNOS(+) nerve fibers were closely aligned with both ICC-IM and PDGFRα(+)-IM. An even closer association was seen between ICC-IM and PDGFRα(+)-IM. Thus, a close morphological arrangement exists between inhibitory motor neurons, ICC-IM and PDGFRα(+)-IM suggesting that some functional interaction occurs between them contributing to inhibitory neurotransmission in the IAS.

  7. Establishment and characterization of a fibroblast-like cell line from Anabarilius grahami (Cypriniformes:Cyprinidae)%Establishment and characterization of a fibroblast-like cell line from Anabarilius grahami (Cypriniformes: Cyprinidae)

    Institute of Scientific and Technical Information of China (English)

    Xiaoai WANG; Junxing YANG; Xiaoyong CHEN; Xiaofu PAN

    2012-01-01

    Though Yunnan province contains some 562 known species of fish,no cell lines from any of these have been made available to date.To protect germplasm resources and provide an effective tool in solving problems at cellular level of Anabarilius grahami,a fish endemic to Fuxian Lake,Yunnan,China,we established and characterized the major features of a continuous cell line (AGF Ⅱ) from the caudal fin tissue of A.grahami.This AGF Ⅱ cell line consists of fibroblast-like cells and has been subcultured more than 60 times over the course of a year.The cell line was maintained in DMEM/F12 supplemented with 10% FBS,with a cellular doubling time of 51.1 h.We continued with more experiments to optimize the culture and storage conditions,and found a variety of interesting results: cells could grow at temperature between 24 ℃ and 28 ℃,with the optimal temperature of 28 ℃.Likewise,the growth rate ofA.grahami fin cells increased when the FBS proportion increased from 5% to 20%,with the optimal growth at the concentrations of 20% FBS; cells were able to grow in L-15 and DMEM/F12 with optimal growth at L-15; DMSO is a better cryoprotectant than Glycerol,EG and MeOH for AGFⅡ cells with optimal concentration of 5% DMSO.Chromosome analysis also showed that the distribution of chromosome number varies from 38 to 52,with a modal peak at 48 chromosomes,accounting for 39.8% of all cells.Using the same primer pairs specific to mtDNA,the AGF Ⅱ cell sequences obtained by PCR were identical to those from muscle tissues ofA.grahami.Both chromosome analysis and PCR amplification confirmed the AGF Ⅱ cells were from A.grahami,also indicating that that current long-term artificial propagation ofA.grahami has been successful.Finally,we noted that when cells were transfected with pEYFP-N1 and pECFP-N1 plasmid,bright fluorescent signals were observed,suggesting that this cell line may be suitable for use in transfection and future gene expression studies.

  8. Kit-negative fibroblast-like cells expressing SK3, a Ca2+-activated K+ channel, in the gut musculature in health and disease

    DEFF Research Database (Denmark)

    Vanderwinden, Jean-Marie; Rumessen, Jüri J; de Kerchove d'Exaerde, Alban;

    2002-01-01

    CD34-ir fibroblast-like cells adjacent to, but distinct from, the cells of Cajal remains elusive. The distribution of SK3 was studied by immunohistochemistry in the normal human gut, in motility disorders with a lack of cells of Cajal (infantile hypertrophic pyloric stenosis and Hirschsprung...... were lacking. These cells were CD34-ir fibroblast-like cells in the human gut and in the mouse stomach, while SK3-ir cells in the mouse intestine were CD34 negative. As SK channels are reportedly involved in inhibitory neurotransmission, our morphological observations suggest that SK3-ir interstitial...... cells, distinct from the Kit-ir interstitial cells of Cajal, may represent a novel cellular component in the control of excitability of the digestive musculature. Further studies will be required to directly address the function of these cells....

  9. Influence of Periostin on Synoviocytes in Knee Osteoarthritis

    Science.gov (United States)

    TAJIKA, YUTARO; MOUE, TATSUYA; ISHIKAWA, SHINTARO; ASANO, KAZUHITO; OKUMO, TAKAYUKI; TAKAGI, HIROSHI; HISAMITSU, TADASHI

    2017-01-01

    Background: Periostin (POSTN) is a protein that binds to integrins to support adhesion and migration of epithelial cells. Mice lacking this gene exhibit cardiac valve disease as well as skeletal and dental defects. Recent studies indicated that periostin is involved in the pathogenesis and progression of knee osteoarthritis (OA). We investigated the influence of periostin and matrix metalloproteinases (MMPs) on OA synoviocytes. Materials and Methods: OA patients were classified according to the Kellgren-Lawrence system and the levels of periostin, interleukin (IL)-4, IL-13 and transforming growth factor-β (TGFβ) in the synovial fluid were measured. MMPs or tissue inhibitor of MMPs (TIMPs) with periostin in cultured cells were measured when periostin was added to OA-associated synovial cells. Dexamethasone, a steroid medication which shows immunosuppressive effects, was used to investigate the influence of the downstream cascade. Results: Periostin and IL-13 levels were up-regulated during the progression of OA. MMP-2 and MMP-3 levels increased in a periostin concentration-dependent manner. Increase in MMP-2 and MMP-3 levels was inhibited by dexamethasone treatment. Conclusion: In vivo results herein indicate that IL-13 may induce periostin production in OA. Furthermore, periostin may facilitate MMP production in OA-associated synovial cells. PMID:28064223

  10. Selective Inhibition of Human Group IIA-secreted Phospholipase A2 (hGIIA) Signaling Reveals Arachidonic Acid Metabolism Is Associated with Colocalization of hGIIA to Vimentin in Rheumatoid Synoviocytes*

    Science.gov (United States)

    Lee, Lawrence K.; Bryant, Katherine J.; Bouveret, Romaric; Lei, Pei-Wen; Duff, Anthony P.; Harrop, Stephen J.; Huang, Edwin P.; Harvey, Richard P.; Gelb, Michael H.; Gray, Peter P.; Curmi, Paul M.; Cunningham, Anne M.; Church, W. Bret; Scott, Kieran F.

    2013-01-01

    Human group IIA secreted phospholipase A2 (hGIIA) promotes tumor growth and inflammation and can act independently of its well described catalytic lipase activity via an alternative poorly understood signaling pathway. With six chemically diverse inhibitors we show that it is possible to selectively inhibit hGIIA signaling over catalysis, and x-ray crystal structures illustrate that signaling involves a pharmacologically distinct surface to the catalytic site. We demonstrate in rheumatoid fibroblast-like synoviocytes that non-catalytic signaling is associated with rapid internalization of the enzyme and colocalization with vimentin. Trafficking of exogenous hGIIA was monitored with immunofluorescence studies, which revealed that vimentin localization is disrupted by inhibitors of signaling that belong to a rare class of small molecule inhibitors that modulate protein-protein interactions. This study provides structural and pharmacological evidence for an association between vimentin, hGIIA, and arachidonic acid metabolism in synovial inflammation, avenues for selective interrogation of hGIIA signaling, and new strategies for therapeutic hGIIA inhibitor design. PMID:23482564

  11. Gonococcal arthritis

    Science.gov (United States)

    Disseminated gonococcal infection (DGI); Disseminated gonococcemia; Septic arthritis - gonococcal arthritis ... Gonococcal arthritis is an infection of a joint. It occurs in people who have gonorrhea , which is caused by ...

  12. 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.

  13. 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 ...

  14. 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 ...

  15. Effects of cytokines, growth factors and drugs on matrix metalloproteinases activities of osteoarthritic chondrocytes and synoviocytes

    Institute of Scientific and Technical Information of China (English)

    GUAN Jian-long; HAN Xing-hai; SHI Gui-ying; YUAN Guo-hua

    2001-01-01

    Objective: To evaluate the effects of some cytokines, TGF-β1 and drugs on matrix metalloproteinases (MMPs) activities in culture medium of arthritic chondrocytes and synoviocytes. Methods: The chondrocyte and synoviocyte monolayers isolated from the cartilages and synovial fluids in 10 knee OA patients were treated with IL-1β TGF-β1, TNF-α, diclofenac acid, dexamethasone or doxycycline individually and together for 72 h. Zymography was used to determine the activities of MMP-2 and -9. Results: The chondrocyte monolayers produced MMP-2 and -9, while the synoviocytes only produced MMP-2. The MMP-9 activity was markedly enhanced by IL-1β TNF-α and diclofenac. IL-1β was the most effective stimulus, and had synergistic effect with TNF-α or diclifenac. MMP-2 activity was not affected. Doxcycline, TGF-β1 and dexamethasone could depress the activities of MMP-9 and MMP-2, and antagonize the enhancing effect of IL-1β TNF-α or diclofenac. Conclusion: IL-1β and TNF-α may play important roles degrading OA cartilage, while TGF-β1 and doxycycline may be protective factors.

  16. Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro.

    Science.gov (United States)

    Ma, Xiaoyang; Chen, Jia; Xu, Bei; Long, Xiao; Qin, Han; Zhao, Robert Chunhua; Wang, Xiaojun

    2015-05-01

    A keloid scar is an overgrowth of dense fibrous tissue that develops around a wound. These scars are raised scars that spread beyong the margins of the orinigal wound to normal skin by invasion. Keloid tissue consists of both an epithelium and dermal fibroblasts. Recent studies have primarily focused on keloid fibroblasts; however, the precise role of keratinocytes in the invasion process of keloids remains to be identified. Hypoxia is a typical characteristic of keloid scars, as well as other solid tumors. The expression of the transcription factor, hypoxia-inducible factor-1α (HIF-1α), is mainly induced by hypoxia and is known for its ability to induce proliferative and transformative changes in cells; its expression has been shown to correlate with tumor invasion and metastasis. In the present study, we used immunohistochemistry, fluorescence staining and western blot analysis and demonstrated that HIF-1α was highly expressed in both the epithelial layer of keloid tissue specimens and in hypoxia-exposed keratinocytes, which suggested that the keloid keratinocytes underwent epithelial-to-mesenchymal transition (EMT) in vitro. The high expression of mesenchymal markers, such as as vimentin and fibronectin was confirmed, as well as the reduced expression of E-cadherin and zonula occludens-1 (ZO-1) during this process by detection at the protein and mRNA level. Moreover, siRNA targeting HIF-1α reversed the changes which had occurred in the morphology of the keratinocytes (cells had acquired a fibroblast-like appearance) and suppressed the invasive ability of the keratinocytes. In conclusion, the present findings demonstrate that the hypoxia/HIF-1α microenvironment provides a favorable environment for keloid-derived keratinocytes to adopt a fibroblast-like appearance through EMT. This transition may be responsible for the enhanced capacity of keloid keratinocytes to invade, allowing the keloids to extend beyond the wound margin.

  17. 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 ...

  18. 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 ...

  19. Thumb Arthritis

    Science.gov (United States)

    ... Media Find a Hand Surgeon Home Anatomy Thumb Arthritis Email to a friend * required fields From * To * ... A joint is where bones connect and move. Arthritis is thinning of the cartilage, which is the ...

  20. 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 ...

  1. 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.

  2. 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 ...

  3. Alternative for anti-TNF antibodies for arthritis treatment.

    Science.gov (United States)

    Paquet, Joseph; Henrionnet, Christel; Pinzano, Astrid; Vincourt, Jean-Baptiste; Gillet, Pierre; Netter, Patrick; Chary-Valckenaere, Isabelle; Loeuille, Damien; Pourel, Jacques; Grossin, Laurent

    2011-10-01

    Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, plays a key role in the pathogenesis of many inflammatory diseases, including arthritis. Neutralization of this cytokine by anti-TNF-α antibodies has shown its efficacy in rheumatoid arthritis (RA) and is now widely used. Nevertheless, some patients currently treated with anti-TNF-α remain refractory or become nonresponder to these treatments. In this context, there is a need for new or complementary therapeutic strategies. In this study, we investigated in vitro and in vivo anti-inflammatory potentialities of an anti-TNF-α triplex-forming oligonucleotide (TFO), as judged from effects on two rat arthritis models. The inhibitory activity of this TFO on articular cells (synoviocytes and chondrocytes) was verified and compared to that of small interfering RNA (siRNA) in vitro. The use of the anti-TNF-α TFO as a preventive and local treatment in both acute and chronic arthritis models significantly reduced disease development. Furthermore, the TFO efficiently blocked synovitis and cartilage and bone destruction in the joints. The results presented here provide the first evidence that gene targeting by anti-TNF-α TFO modulates arthritis in vivo, thus providing proof-of-concept that it could be used as therapeutic tool for TNF-α-dependent inflammatory disorders.

  4. Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium.

    Science.gov (United States)

    Hur, Woojune; Lee, Hoon Young; Min, Hye Sook; Wufuer, Maierdanjiang; Lee, Chang-Won; Hur, Ji An; Kim, Sang Hyon; Kim, Byeung Kyu; Choi, Tae Hyun

    2017-04-20

    Fibroblasts are ubiquitous cells in the human body and are absolutely necessary for wound healing such as for injured skin. This role of fibroblasts was the reason why we aimed to differentiate human adipose-derived stem cells (hADSCs) into fibroblasts and to test their wound healing potency. Recent reports on hADSC-derived conditioned medium have indicated stimulation of collagen synthesis as well as migration of dermal fibroblasts in wound sites with these cells. Similarly, human fibroblast-derived conditioned medium (F-CM) was reported to contain a variety of factors known to be important for growth of skin. However, it remains unknown whether and how F-CM can stimulate hADSCs to secrete type I collagen. In this study, we obtained F-CM from the culture of human skin fibroblast HS27 cells in DMEM media. For an in-vivo wound healing assay using cell transplantation, balb/c nude mice with full-thickness skin wound were used. Our data showed that levels of type I pro-collagen secreted by hADSCs cultured in F-CM increased significantly compared with hADSCs kept in normal medium for 72 h. In addition, from a Sircol collagen assay, the amount of collagen in F-CM-treated hADSC conditioned media (72 h) was markedly higher than both the normal medium-treated hADSC conditioned media (72 h) and the F-CM (24 h). We aimed to confirm that hADSCs in F-CM would differentiate into fibroblast cells in order to stimulate wound healing in a skin defect model. To investigate whether F-CM induced hADSCs into fibroblast-like cells, we performed FACS analysis and verified that both F-CM-treated hADSCs and HS27 cells contained similar expression patterns for CD13, CD54, and CD105, whereas normal medium-treated hADSCs were significantly different. mRNA level  analysis for Nanog, Oct4A, and Sox2 as undifferentiation markers and vimentin, HSP47, and desmin as matured fibroblast markers supported the characterization that hADSCs in F-CM were highly differentiated into fibroblast-like

  5. 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 ...

  6. Sex and Arthritis

    Science.gov (United States)

    ... Well with Rheumatic Disease Sex & Arthritis Sex and Arthritis Fast Facts Sex and arthritis can coexist. Open ... ability for sexual expression and enjoyment. Impact of Arthritis on Sexual Expression Aspects of arthritis which can ...

  7. 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.

  8. 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

  9. Ionizing radiation accelerates Drp1-dependent mitochondrial fission, which involves delayed mitochondrial reactive oxygen species production in normal human fibroblast-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Kobashigawa, Shinko, E-mail: kobashin@nagasaki-u.ac.jp [Atomic Bomb Disease Institute, Course of Life Sciences and Radiation Research, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Yamashita, Shunichi [Atomic Bomb Disease Institute, Course of Life Sciences and Radiation Research, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer We report first time that ionizing radiation induces mitochondrial dynamic changes. Black-Right-Pointing-Pointer Radiation-induced mitochondrial fission was caused by Drp1 localization. Black-Right-Pointing-Pointer We found that radiation causes delayed ROS from mitochondria. Black-Right-Pointing-Pointer Down regulation of Drp1 rescued mitochondrial dysfunction after radiation exposure. -- Abstract: Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial O{sub 2}{sup {center_dot}-} production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial O{sub 2}{sup {center_dot}-}. Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation.

  10. Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells.

    Science.gov (United States)

    Jang, Bohee; Jung, Hyejung; Chung, Heesung; Moon, Byung-In; Oh, Eok-Soo

    2016-08-12

    E-cadherin plays a mechanical role in mediating cell-cell interactions and maintaining epithelial tissue integrity, and the loss of E-cadherin function has been implicated in cancer progression and metastasis. Syndecan-2, a cell-surface heparan sulfate proteoglycan, is upregulated during the development of colon cancer. Here, we assessed the functional relationship between E-cadherin and syndecan-2. We found that stable overexpression of syndecan-2 in a human colorectal adenocarcinoma cell line (HT29) enhanced the proteolytic shedding of E-cadherin to conditioned-media. Either knockdown of matrix metalloproteinase 7 (MMP-7) or inhibition of MMP-7 activity using GM6001 significantly reduced the extracellular shedding of E-cadherin, suggesting that syndecan-2 mediates E-cadherin shedding via MMP-7. Consistent with this notion, enhancement of MMP-7 expression by interleukin-1α treatment increased the shedding of E-cadherin. Conversely, the specific reduction of either syndecan-2 or MMP-7 reduced the shedding of E-cadherin. HT29 cells overexpressing syndecan-2 showed significantly lower cell-surface expression of E-cadherin, decreased cell-cell contact, a more fibroblastic cell morphology, and increased expression levels of ZEB-1. Taken together, these data suggest that syndecan-2 induces extracellular shedding of E-cadherin and supports the acquisition of a fibroblast-like morphology by regulating MMP-7 expression in a colon cancer cell line.

  11. Monoarticular Arthritis.

    Science.gov (United States)

    Singh, Namrata; Vogelgesang, Scott A

    2017-05-01

    Monoarticular arthritis is inflammation characterized by joint pain, swelling, and sometimes periarticular erythema. Although chronic causes are seen, the onset is often acute. An infected joint can quickly lead to permanent damage, making it a medical emergency. However, acute gout presenting as monoarticular arthritis is often so uncomfortable it requires urgent attention. Monoarticular crystalline arthritis is common and a septic joint is a medical emergency so it is no surprise that these diagnoses come to mind with complaint of inflammation in 1 joint. However, there are many causes of monoarticular arthritis that clinicians must consider. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Cucurbitacin E inhibits TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via suppression of PI3K/Akt/NF-κB pathways.

    Science.gov (United States)

    Jia, Qingyun; Cheng, Wenxiang; Yue, Ye; Hu, Yipping; Zhang, Jian; Pan, Xiaohua; Xu, Zhanwang; Zhang, Peng

    2015-12-01

    Increasing studies indicated that Cucurbitacin E (CuE), a compound isolated from Cucurbitaceae, has been shown anti-inflammatory effect. However, the effect of CuE on rheumatoid arthritis (RA) inflammatory response and its potential molecular mechanism are still unknown. In this study, we demonstrated that CuE significantly suppressed TNF-α-induced inflammatory cytokines production interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) mRNA and protein expression in human synoviocyte MH7A cells. Furthermore, we found that CuE also inhibited TNF-α-induced phosphorylation of NF-κBp65, IKKα/β, and IκBα in a dose-and time-dependent manner as well as NF-κBp65 nuclear translocation. Finally, we showed that CuE blocked the upstream targets of NF-κB pathway RIP1/PI3K/Akt. Interestingly, PI3K inhibitor LY294002 completely blocked the TNF-α-induced activation of p85, Akt and the whole cascade of the NF-κB signaling components and suppressed inflammatory cytokines production in mRNA and protein levels similarly as CuE. Our studies provided the first evidence that CuE inhibited TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via modulation of PI3K/Akt/NF-κB pathway. These findings indicated that CuE is a potential candidate for RA therapy.

  13. Effects of flunixin, tolfenamic acid, R(-) and S(+) ketoprofen on the response of equine synoviocytes to lipopolysaccharide stimulation.

    Science.gov (United States)

    Landoni, M F; Foot, R; Frean, S; Lees, P

    1996-11-01

    The objective of this study was to analyse the effects of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) on the production of beta-glucuronidase (beta-glu), tumour necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated equine synoviocytes. The agents studied were flunixin, tolfenamic acid, S(+)ketoprofen (KTP) and R(-)ketoprofen. LPS-induced release of beta-glu from synoviocytes was inhibited in a concentration dependent manner by all 4 compounds, tolfenamic acid being the most potent. Of the 2 KTP enantiomers, S(+)KTP exerted the greatest inhibitory effect. Tolfenamic acid and flunixin increased the production of IL-6-like activity by LPS-stimulated synoviocytes only at the highest concentration studied (1000 mumol/l). Lower concentrations produced no effect on IL-6. Flunixin, tolfenamic acid and S(+)KTP produced statistically significant and concentration related increases in the release of IL-1-like activity by LPS-stimulated synoviocytes. Prostaglandin E2 synthesis was markedly inhibited in a concentration dependent manner by the 4 NSAIDs. However, R(-)KTP was effective only at the highest concentrations investigated (1000 and 100 mumol/l). The present findings are compatible with the possibility that longterm use of NSAIDs in arthropathies, by removing the regulator role of PGE2 on IL-1 synthesis, might enhance the pathological process of cartilage degeneration.

  14. Fibrochondrogenic potential of synoviocytes from osteoarthritic and normal joints cultured as tensioned bioscaffolds for meniscal tissue engineering in dogs

    Directory of Open Access Journals (Sweden)

    Jennifer J. Warnock

    2014-09-01

    Full Text Available Meniscal tears are a common cause of stifle lameness in dogs. Use of autologous synoviocytes from the affected stifle is an attractive cell source for tissue engineering replacement fibrocartilage. However, the diseased state of these cells may impede in vitro fibrocartilage formation. Synoviocytes from 12 osteoarthritic (“oaTSB” and 6 normal joints (“nTSB” were cultured as tensioned bioscaffolds and compared for their ability to synthesize fibrocartilage sheets. Gene expression of collagens type I and II were higher and expression of interleukin-6 was lower in oaTSB versus nTSB. Compared with nTSB, oaTSB had more glycosaminoglycan and alpha smooth muscle staining and less collagen I and II staining on histologic analysis, whereas collagen and glycosaminoglycan quantities were similar. In conclusion, osteoarthritic joint—origin synoviocytes can produce extracellular matrix components of meniscal fibrocartilage at similar levels to normal joint—origin synoviocytes, which makes them a potential cell source for canine meniscal tissue engineering.

  15. Does Platelet-Rich Plasma Freeze-Thawing Influence Growth Factor Release and Their Effects on Chondrocytes and Synoviocytes?

    Directory of Open Access Journals (Sweden)

    Alice Roffi

    2014-01-01

    Full Text Available PRP cryopreservation remains a controversial point. Our purpose was to investigate the effect of freezing/thawing on PRP molecule release, and its effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from 10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1β, HGF, PDGF AB/BB, TGF-β1, and VEGF were assayed 1 hour and 7 days after activation. Culture media of chondrocytes and synoviocytes were supplemented with fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted proteins levels were evaluated. Results showed that in the freeze-thawed PRP the immediate and delayed molecule releases were similar or slightly lower than those in fresh PRP. TGF-β1 and PDGF AB/BB concentrations were significantly reduced after freezing both at 1 hour and at 7 days, whereas HGF concentration was significantly lower in frozen PRP at 7 days. In fresh PRP IL-1β and HGF concentrations underwent a significant further increase after 7 days. Similar gene expression was found in chondrocytes cultured with both PRPs, whereas in synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation is a safe procedure, which sufficiently preserves PRP quality and its ability to induce proliferation and the production of ECM components in chondrocytes and synoviocytes.

  16. Influence of IL13 on Periostin Secretion by Synoviocytes in Osteoarthritis

    Science.gov (United States)

    MOUE, TATSUYA; TAJIKA, YUTARO; ISHIKAWA, SHINTARO; KANADA, YASUAKI; OKUMO, TAKAYUKI; ASANO, KAZUHITO; HISAMITSU, TADASHI

    2017-01-01

    Background: Our previous research provided evidence of periostin increase in parallel with interleukin-13 (IL13) increase in the synovial fluid of patients with osteoarthritis (OA). The reaction cascade from IL13 to periostin, however, remains unidentified. We, therefore, tested the hypothesis that periostin secretion is affected downstream of IL13. Materials and Methods: OA synoviocytes were cultured under different concentrations of IL13. Periostin content in culture supernatants and the level of signal transducer and activator of transcription 6 (STAT6) in the cultured cells were measured using enzyme-linked immunosorbent assay (ELISA). Moreover, the influence of dexamethasone and leflunomide on periostin production in relation to the effect of IL13 on the cells was also examined. Results: Periostin content in culture supernatants and the level of STAT6 in cultured cells were significantly increased by IL13. The increase of periostin was significantly inhibited by dexamethasone and leflunomide. Conclusion: Periostin may be up-regulated in OA synoviocytes via STAT6 downstream of IL13. PMID:28064224

  17. Adult human brain neural progenitor cells (NPCs and fibroblast-like cells have similar properties in vitro but only NPCs differentiate into neurons.

    Directory of Open Access Journals (Sweden)

    Thomas In-Hyeup Park

    Full Text Available The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia, and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs. These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5-6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting Ah

  18. Enhanced migration of murine fibroblast-like 3T3-L1 preadipocytes on type I collagen-coated dish is reversed by silibinin treatment.

    Science.gov (United States)

    Liu, Xiaoling; Xu, Qian; Liu, Weiwei; Yao, Guodong; Zhao, Yeli; Xu, Fanxing; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-Ichi; Onodera, Satoshi; Yamato, Masayuki; Ikejima, Takashi

    2017-09-20

    Migration of fibroblast-like preadipocytes is important for the development of adipose tissue, whereas excessive migration is often responsible for impaired adipose tissue related with obesity and fibrotic diseases. Type I collagen (collagen I) is the most abundant component of extracellular matrix and has been shown to regulate fibroblast migration in vitro, but its role in adipose tissue is not known. Silibinin is a bioactive natural flavonoid with antioxidant and antimetastasis activities. In this study, we found that type I collagen coating promoted the proliferation and migration of murine 3T3-L1 preadipocytes in a dose-dependent manner, implying that collagen I could be an extracellular signal. Regarding the mechanisms of collagen I-stimulated 3T3-L1 migration, we found that NF-κB p65 is activated, including the increased nuclear translocation of NF-κB p65 as well as the upregulation of NF-κB p65 phosphorylation and acetylation, accompanied by the increased expressions of proinflammatory factors and the generation of reactive oxygen species (ROS). Reduction of collagen I-enhanced migration of cells by treatment with silibinin was associated with suppression of NF-κB p65 activity and ROS generation, and negatively correlated with the increasing sirt1 expression. Taken together, the enhanced migration of 3T3-L1 cells induced on collagen I-coated dish is mediated by the activation of NF-κB p65 function and ROS generation that can be alleviated with silibinin by upregulation of sirt1, leading to the repression of NF-κB p65 function and ROS generation.

  19. Anti-adjuvant arthritis of recombinant human endostatin in rats via inhibition of angiogenesis and proinflammatory factors

    Institute of Scientific and Technical Information of China (English)

    Li YUE; Hua WANG; Li-hua LIU; Yu-xian SHEN; Wei WEI

    2004-01-01

    AIM: To investigate the profile of endostatin on adjuvant arthritis (AA) and angiogenesis blockade in synovitis.METHODS: The model of rat AA was induced by injection of intradermal complete Freund's adjuvant (CFA). Hind paw volume of rat was measured by volume meter and the activities of interleukin- 1 (IL- 1) and IL-2 Were measured by the assay of thymocytes proliferation. IL-1 β and tumor necrosis factor-α (TNF-α) produced by synoviocytes was estimated with radioimmunoassay. The number of new blood vessels in knee joint synovium was counted under microscope by hematoxylin and eosin (HE) staining. RESULTS: The secondary inflammation of AA rats appeared on the 10th day after injection of CFA. The therapeutic administration of endostatin (0.1, 0.5, and 2.5secondary paw swelling and the number of new blood vessels in the synovium of AA rats. Endostatin significantly decreased the production of IL-1 derived from both peritoneal macrophages and synoviocytes and IL-2 from splenocytes, especially at the dose of 2.5 mg/kg. This effect of endostatin also was seen on TNF-α produced by synoviocytes. CONCLUSION: The recombinant human endostatin had an inhibitory effect on rat AA, which was related to its anti-angiogenesis and inhibition of proinflammatory cytokines.

  20. Arthritis and the Feet

    Science.gov (United States)

    ... RSS Home » Learn About Feet » Foot Health Information Arthritis What is Arthritis? Arthritis, in general terms, is inflammation and swelling of ... an increase in the fluid in the joints. Arthritis has multiple causes; just as a sore throat ...

  1. Periploca forrestii Saponin Ameliorates Murine CFA-Induced Arthritis by Suppressing Cytokine Production.

    Science.gov (United States)

    Liu, Yingqin; Li, Minghui; He, Qiuhong; Yang, Xinping; Ruan, Fang; Sun, Guangchen

    2016-01-01

    Periploca forrestii Schltr. has been used as a Chinese folk medicine due to its versatile pharmacological effects such as promoting wounds and rheumatoid arthritis. However, the antiarthritic activity of Periploca forrestii saponin (PFS) and its active compound Periplocin has still not been demonstrated. Here, we evaluated the antiarthritic effects of PFS in adjuvant-induced arthritis (AIA) rats by intragastric administration at a dose of 50 mg/kg. The anti-inflammatory activities of Periplocin were also examined in LPS-induced AIA splenocytes and synoviocytes. PFS significantly ameliorated joint swelling; inhibited bone erosion in joints; lowered levels of IL-6 and TGF-β1 in AIA rat splenocyte; and reduced joint protein expression levels of phospho-STAT3 and IKKα. Using LPS-induced AIA splenocytes, we demonstrate that Periplocin suppressed the key proinflammatory cytokines levels of IL-6, IFN-γ, TGF-β1, and IL-13 and IL-22 and transcription factor levels of T-bet, GATA3, and C-Jun genes. Periplocin also suppressed LPS-induced cytokine secretion from synoviocytes. Our study highlights the antiarthritic activity of PFS and its derived Periplocin and the underlying mechanisms. These results provide a strong rationale for further testing and validation of the use of Periploca forrestii Schltr. as an alternative modality for the treatment of RA.

  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. Rheumatoid arthritis

    African Journals Online (AJOL)

    Mahmood Ally

    ... therapy in RA. Keywords: immune, inflammatory, rheumatoid arthritis, therapy ... are more sensitive and care needs to be taken to exclude viral infections, conditions .... RF is an antibody to immunoglobulin G, seen in 80–90% of patients with ...

  4. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... is Happening to the Joints? Rheumatoid Arthritis: Gaining Control – Working with your Rheumatologist Rheumatoid Arthritis: Additional Conditions ... Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients ...

  5. 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 ...

  6. 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...

  7. Prostaglandin E1 inhibits collagenase gene expression in rabbit synoviocytes and human fibroblasts.

    Science.gov (United States)

    Salvatori, R; Guidon, P T; Rapuano, B E; Bockman, R S

    1992-07-01

    Cartilage breakdown, as seen in inflammatory and degenerative joint diseases, can be mediated by proteolytic enzymes, such as the metalloproteinase collagenase, the only enzyme able to digest collagen at neutral pH. In vitro collagenase gene expression can be stimulated by the phorbol ester tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. We have investigated the effect of prostaglandin E1 (PGE1) on 12-O-tetradecanoyl-phorbol-13-acetate-stimulated collagenase mRNA levels in the rabbit synoviocyte cell line HIG-82. PGE1, but not PGE2 or PGF2 alpha, was able to selectively reduce collagenase mRNA levels in a dose-dependent fashion. PGE1 markedly increased intracellular levels of cAMP, while PGE2 and PGF2 alpha had little or no effect on cAMP production in the HIG-82 synoviocytes. Agents known to increase intracellular cAMP levels, such as the adenyl cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), mimicked the effect of PGE1, on collagenase mRNA levels. PGE1, forskolin, and IBMX also decreased collagenase mRNA levels in human skin fibroblasts, demonstrating that this observation was not unique to the HIG-82 cell line. Transient transfection experiments carried out in HIG-82 cells using a 1.2-kilobase portion of the 5'-flanking region of the human collagenase gene linked to the reporter gene luciferase demonstrated that PGE1, forskolin, and IBMX exert their inhibitory effect on the promoter region of the collagenase gene.

  8. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis Information Disease Information Rheumatoid Arthritis Psoriatic Arthritis Ankylosing Spondylitis Osteoarthritis Gout Lyme Disease Osteoporosis News Rheumatoid Arthritis ...

  9. 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 ...

  10. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid ...

  11. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available Appointments • Support Our Research Arthritis Information Disease Information Rheumatoid Arthritis Psoriatic Arthritis Ankylosing Spondylitis Osteoarthritis Gout Lyme Disease Osteoporosis News Rheumatoid Arthritis News ...

  12. 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 ...

  13. 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.

  14. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of ... on this website. Copyright Johns Hopkins Arthritis Center © 2017 Patient Privacy Johns Hopkins Rheumatology

  15. 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. ...

  16. Arthritis in America

    Science.gov (United States)

    ... Digital Press Kit Read the MMWR Science Clips Arthritis in America Time to Take Action! Language: English ( ... by about 40% by being physically active. Problem Arthritis is common and a growing health threat. Arthritis ...

  17. Arthritis: Frequently Asked Questions

    Science.gov (United States)

    ... Recommend on Facebook Tweet Share Compartir What is Arthritis? The word arthritis actually means joint inflammation, but ... provided for you. Who is at risk for arthritis? Certain factors are associated with a greater risk ...

  18. Juvenil idiopatisk arthritis

    DEFF Research Database (Denmark)

    Herlin, Troels

    2002-01-01

    The new classification of juvenile idiopathic arthritis (JIA) is described in this review. Clinical characteristics divide JIA in to subtypes: systemic, oligoarticular (persistent and extended type), RF-positive and--negative polyarticular, enthesitis-related arthritis and psoriatic arthritis...

  19. 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 ...

  20. Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

    Institute of Scientific and Technical Information of China (English)

    Yan-li LIU; Hai-ming LIN; Rong ZOU; Jun-chao WU; Rong HAN; Laurence N RAYMOND; Paul F REID; Zheng-hong QIN

    2009-01-01

    Aim:Cobratoxin (CTX),the long-chain α-neurotoxin from Thailand cobra venom,has been demonstrated to have analgesic action in rodent pain models.The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adju-vant arthritis (AA) in rats.Methods: Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats.Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration.Tumor necrosis factor-a (TNF-α),interleukin-1 (IL-1),interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA.Histopathological changes in synoviocytes were examined under a microscope.Involvement of the cholinergic system in the effects of CTX was examinedby pretreatment of animals with the α7 nicotinic receptor (α7-nAChR) antagonist methyllycaconitine (MLA).Results: CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal.The lev-els of TNF-α,IL-1 and IL-2 in the serum of AA rats were increased,whereas the level of IL-10 was decreased.Histopathologi-cal examination of synoviocytes showed pronounced inflammation and accumulation of collagen.The administration of CTX (17.0 μg/kg,ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia.CTX also reduced the produc-tion ofTNF-α,IL-1,and IL-2 but increased the production of IL-10 and altered pathohistological changes.The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg,sc).Conclusion: These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines,α7-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

  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. 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.

  3. 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.

  4. Midcarpal and STT Arthritis in Patients With CMC Arthritis

    National Research Council Canada - National Science Library

    Katzel, Evan B; Shakir, Sameer; Fowler, John; Buterbaugh, Glenn A; Imbriglia, Joseph E

    2016-01-01

    .... The prevalence of midcarpal arthritis in patients with basal joint arthritis is unknown. The goal of this study is to establish the radiographic prevalence of midcarpal arthritis in patients with CMC arthritis and/or STT...

  5. Human synoviocyte lubricin and bovine synovial fluid lubricin equally improve gliding resistance in a canine model in vitro.

    Science.gov (United States)

    Kohn, Mark D; Sun, Yu-long; Zhao, Chunfeng; Thoreson, Andrew R; Jay, Gregory D; An, Kai-Nan; Amadio, Peter C

    2011-01-01

    The lubricating ability of human synoviocyte lubricin and bovine lubricin purified from synovial fluid was investigated and compared using a canine in vitro tendon model. Our null hypothesis was that these two forms of lubricin would have equal lubricating ability. Forty two canine hind-limbs were used. The peroneus longus (PL) tendons were harvested, along with the proximal phalanx and flexor digitorum profundus of the second or fifth digit with its proximal fibro-osseous pulley. Forty PL tendons were randomly assigned to one of four treatment groups. After gliding resistance testing, two intact PL tendons and two tendons in each group were randomly selected for surface observation with scanning electron microscopy (SEM). The variance of the PL saline group mean gliding resistance was significantly different from other groups. There was a significant treatment-cycle interaction effect on the mean gliding resistance. On SEM, the surface of the saline treated PL tendons appeared rough, whereas the other tendon surfaces appeared smooth. Human synoviocyte lubricin functioned as well as bovine synovial fluid lubricin to reduce friction of canine PL tendons in vitro. This data suggest that treatment using the two forms of lubricin are mechanically similar.

  6. [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.

  7. Synoviocyte Derived-Extracellular Matrix Enhances Human Articular Chondrocyte Proliferation and Maintains Re-Differentiation Capacity at Both Low and Atmospheric Oxygen Tensions.

    Directory of Open Access Journals (Sweden)

    Thomas J Kean

    Full Text Available Current tissue engineering methods are insufficient for total joint resurfacing, and chondrocytes undergo de-differentiation when expanded on tissue culture plastic. De-differentiated chondrocytes show poor re-differentiation in culture, giving reduced glycosaminoglycan (GAG and collagen matrix accumulation. To address this, porcine synoviocyte-derived extracellular matrix and low (5% oxygen tension were assessed for their ability to enhance human articular chondrocyte expansion and maintain re-differentiation potential.Porcine synoviocyte matrices were devitalized using 3 non-detergent methods. These devitalized synoviocyte matrices were compared against tissue culture plastic for their ability to support human chondrocyte expansion. Expansion was further compared at both low (5%, and atmospheric (20% oxygen tension on all surfaces. Expanded cells then underwent chondrogenic re-differentiation in aggregate culture at both low and atmospheric oxygen tension. Aggregates were assessed for their GAG and collagen content both biochemically and histologically.Human chondrocytes expanded twice as fast on devitalized synoviocyte matrix vs. tissue culture plastic, and cells retained their re-differentiation capacity for twice the number of population doublings. There was no significant difference in growth rate between low and atmospheric oxygen tension. There was significantly less collagen type I, collagen type II, aggrecan and more MMP13 expression in cells expanded on synoviocyte matrix vs. tissue culture plastic. There were also significant effects due to oxygen tension on gene expression, wherein there was greater collagen type I, collagen type II, SOX9 and less MMP13 expression on tissue culture plastic compared to synoviocyte matrix. There was a significant increase in GAG, but not collagen, accumulation in chondrocyte aggregates re-differentiated at low oxygen tension over that achieved in atmospheric oxygen conditions.Synoviocyte

  8. Il-4 and IL-13, but not IL-10, protect human synoviocytes from apoptosis.

    NARCIS (Netherlands)

    Relic, B.; Guicheux, J.; Mezin, F.; Lubberts, G.J.H.; Togninalli, D.; Garcia, I.; Berg, W.B. van den; Guerne, P.A.

    2001-01-01

    Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the abili

  9. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Patient Webcasts / Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos ... member of our patient care team. Managing Your Arthritis Managing Your Arthritis Managing Chronic Pain and Depression ...

  10. Rheumatoid Arthritis Educational Video Series

    Science.gov (United States)

    ... Patient Webcasts / Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos ... member of our patient care team. Managing Your Arthritis Managing Your Arthritis Managing Chronic Pain and Depression ...

  11. Tumor necrosis factor-alpha (TNF-α enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes

    Directory of Open Access Journals (Sweden)

    Ma Fei

    2009-08-01

    Full Text Available Abstract Background We have shown functional expression of several TRP channels on human synovial cells, proposing significance in known calcium dependent proliferative and secretory responses in joint inflammation. The present study further characterizes synoviocyte TRP expression and activation responses to thermal and osmotic stimuli after pre-treatment with proinflammatory mediator tumor necrosis factor alpha (TNF-α, EC50 1.3221 × 10-10g/L. Results Fluorescent imaging of Fura-2 loaded human SW982 synoviocytes reveals immediate and delayed cytosolic calcium oscillations elicited by (1 TRPV1 agonists capsaicin and resiniferatoxin (20 – 40% of cells, (2 moderate and noxious temperature change, and (3 osmotic stress TRPV4 activation (11.5% of cells. TNF-alpha pre-treatment (1 ng/ml, 8 – 16 hr significantly increases (doubles capsaicin responsive cell numbers and [Ca2+]i spike frequency, as well as enhances average amplitude of temperature induced [Ca2+]i responses. With TNF-alpha pre-treatment for 8, 12, and 16 hr, activation with 36 or 45 degree bath solution induces bimodal [Ca2+]i increase (temperature controlled chamber. Initial temperature induced rapid transient spikes and subsequent slower rise reflect TRPV1 and TRPV4 channel activation, respectively. Only after prolonged TNF-alpha exposure (12 and 16 hr is recruitment of synoviocytes observed with sensitized TRPV4 responses to hypoosmolarity (3–4 fold increase. TNF-alpha increases TRPV1 (8 hr peak and TRPV4 (12 hr peak immunostaining, mRNA and protein expression, with a TRPV1 shift to membrane fractions. Conclusion TNF-α provides differentially enhanced synoviocyte TRPV1 and TRPV4 expression and [Ca2+]i response dependent on the TRP stimulus and time after exposure. Augmented relevance of TRPV1 and TRPV4 as inflammatory conditions persist would provide calcium mediated cell signaling required for pathophysiological responses of synoviocytes in inflammatory pain states.

  12. Folate Deficiency Triggered Apoptosis of Synoviocytes: Role of Overproduction of Reactive Oxygen Species Generated via NADPH Oxidase/Mitochondrial Complex II and Calcium Perturbation.

    Science.gov (United States)

    Hsu, Hung-Chih; Chang, Wen-Ming; Wu, Jin-Yi; Huang, Chin-Chin; Lu, Fung-Jou; Chuang, Yi-Wen; Chang, Pey-Jium; Chen, Kai-Hua; Hong, Chang-Zern; Yeh, Rang-Hui; Liu, Tsan-Zon; Chen, Ching-Hsein

    2016-01-01

    Despite a plethora of literature has documented that osteoarthritis (OA) is veritably associated with oxidative stress-mediated chondrocyte death and matrix degradation, yet the possible involvement of synoviocyte abnormality as causative factor of OA has not been thoroughly investigated. For this reason, we conduct the current studies to insight into how synoviocytes could respond to an episode of folate-deprived (FD) condition. First, when HIG-82 synoviocytes were cultivated under FD condition, a time-dependent growth impediment was observed and the demise of these cells was demonstrated to be apoptotic in nature mediated through FD-evoked overproduction of reactive oxygen species (ROS) and drastically released of cytosolic calcium (Ca2+) concentrations. Next, we uncovered that FD-evoked ROS overproduction could only be strongly suppressed by either mitochondrial complex II inhibitors (TTFA and carboxin) or NADPH oxidase (NOX) inhibitors (AEBSF and apocynin), but not by mitochondrial complex I inhibitor (rotenone) and mitochondrial complex III inhibitor (antimycin A). Interestingly, this selective inhibition of FD-evoked ROS by mitochondrial complex II and NOX inhibitors was found to correlate excellently with the suppression of cytosolic Ca2+ release and reduced the magnitude of the apoptotic TUNEL-positive cells. Taken together, we present the first evidence here that FD-triggered ROS overproduction in synoviocytes is originated from mitochondrial complex II and NOX. Both elevated ROS in tandem with cytosolic Ca2+ overload serve as final arbitrators for apoptotic lethality of synoviocytes cultivated under FD condition. Thus, folate supplementation may be beneficial to patients with OA.

  13. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis Center since 2000, currently serving as the Nurse Manager. She is a critical member of our patient care team. Managing Your Arthritis Managing Your Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of ...

  14. What Is Juvenile Arthritis?

    Science.gov (United States)

    ... Analgesics for Osteoarthritis (Report from AHRQ) Joint Replacement Surgery: Health Information Basics for You and Your Family NIH Pediatric Rheumatology Clinic Health Information Juvenile Arthritis Find a Clinical Trial Journal Articles Juvenile Arthritis PDF Version Size: 123 KB ...

  15. MP Joint Arthritis

    Science.gov (United States)

    ... Find a Hand Surgeon Home Anatomy MP Joint Arthritis Email to a friend * required fields From * To * ... important for both pinching and gripping. MP joint arthritis is most common in the thumb and index ...

  16. Juvenile idiopathic arthritis

    Science.gov (United States)

    Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ... The cause of juvenile idiopathic arthritis (JIA) is not known. It ... illness . This means the body attacks and destroys healthy body ...

  17. 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 ...

  18. 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...

  19. 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 ...

  20. 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: ...

  1. 99Tc-亚甲基二膦酸盐对胶原诱导性关节炎大鼠滑膜及软骨凋亡相关因子的影响%Effects of 99Tc-MDP on synoviocytes and articular chondrocytes apoptosis associated factors on CIA rats

    Institute of Scientific and Technical Information of China (English)

    胡绍先; 孔芳; 柯丹; 苏敏; 雷小妹; 涂巍; 沈桂芬; 何培根

    2009-01-01

    and the therapeutic targets of RA. This paper was to investigate the therapeutic action of 99Tc-methylene diphosphonic acid (MDP) on CIA rats and its effects on the expression of apoptosis associated factor bcl-2 and bax in synoviocytes and articular chon-drocytes. Methods CIA rat models were carried out by subcutaneous injection with bovine collagen Ⅱ and incomplete Freud's adjuvant. Rats were divided into four groups: control group, CIA model group (the CIA rats were infused with physiological saline via tail vein daily), 99Tc-MDP group (the C1A rats were injected with 99Tc-Mi)P 0.04 μg 99Tc/kg via tail vein daily) and methotrexate (MTX) group (the CIA rats were in-jected with MTX 1 mg/kg via tail vein weekly). The signs of arthritis were evaluated by arthritis index (AI) scores. Immunohistochemistry was performed to detect the expression of bcl-2 and bax in synoviocytes and articular chondrocytes. SPSS 13.0 was used for data analysis. Results (1) The signs of arthritis, AI scores and pathological changes of arthrosynovitis in CIA rats were significantly improved by 99Tc-MDP orMTX. (2) The expression of bcl-2 and box in the synoviocytes of CIA model group [(39.30 ± 0.53) %, (27.37 ±2.45)%] was significantly increased compared with control group [(7.56 ± 1. 18)% , (6.14 ± 1.71) % ; q = 46.27, 24.57, all P < 0.001]. In the synovioeytes of 99Tc-M DP group and MTX group, the level of bcl-2 was remarkably decreased [(30.24 ± 2.09) %, (27.25 ± 3.33) %] compared with CIA model group (q = 13.20, 17.56, all P <0.001), while the level of bax was slightly increased and the ratio of bcl-2/bax was significantly decreased. (3)The expression level of bcl-2 and bax in the articular chondro-cytes of CIA model group [(20.20 ± 2.78) %, (36.40 ± 1.67) %] was significantly higher than control group [(9.91±4.09)%, (6.71 ±3.50)%; q=10.51, 37.01, allP<0.001]. Compared with CIA model group, the expression level of bcl-2 in articular chondrocytes of 99Tc-MDP group [(26. 58 ± 2

  2. 罗格列酮通过抑制 RANKL 及 p-ERK 活化抑制类风湿关节炎破骨细胞的分化及功能%Rosiglitazone inhibits osteoclastogenesis in rheumatoid arthritis by down-regulating RANKL expression and suppressing ERK phosphorylation

    Institute of Scientific and Technical Information of China (English)

    韦秀宁; 郑东辉; 莫颖倩; 马剑达; 戴冽

    2015-01-01

    AIM: To investigate the effects of rosiglitazone on fibroblast-like synoviocyte ( FLS )-induced osteoclastogenesis in rheumatoid arthritis ( RA) and the related mechanism.METHODS: RA-FLS were cocultured with peripheral blood monocytes from healthy volunteers in the presence of macrophage colony-stimulating factor ( M-CSF) and rosiglitazone.Osteoclasts were assayed by tartrate-resistant acid phosphatase ( TRAP) staining.Resorption lacunae area was identified by toluidine blue staining and quantified by image analysis software.The mRNA expression of RANKL and OPG was evaluated by real-time PCR, and the protein levels of RANKL, OPG, p-ERK, p-p38 and p-JNK were measured by Western blot.RESULTS:Compared with control group ( without rosiglitazone treatment) , rosiglitazone at concentration of 15 μmol/L significantly decreased the number of osteoclasts (P0.05 ) . CONCLUSION:Rosiglitazone inhibits RA-FLS-induced osteoclast formation and its resorption activity by down-regulating RANKL expression and ERK phosphorylation, suggesting that rosiglitazone may inhibit RA osteoclastogenesis and bone re-sorption.%目的:探讨罗格列酮(RSG)对类风湿关节炎(RA)成纤维样滑膜细胞(FLS)介导的破骨细胞(Oc)分化及功能的影响及其可能机制。方法:活动期RA患者滑膜体外分离培养FLS,与健康人外周血单核细胞(MNC)共培养,不同浓度RSG (0、5、10和15μmol/L)干预,抗酒石酸酸性磷酸酶(TRAP)染色鉴定Oc并计数;甲苯胺蓝染色和图像分析系统计算骨吸收陷窝面积;Real-time PCR检测共培养体系RANKL和OPG的mRNA表达, Western blot检测RANKL、OPG、p-ERK、p-p38和p-JNK的蛋白含量。结果:与不加RSG组比较,15μmol/L RSG干预后Oc的数量明显减少(P<0.01),骨吸收陷窝面积也减少(P<0.05);共培养体系RANKL的mRNA及蛋白表达明显降低,OPG的mRNA及蛋白表达明显升高(P<0.01);p-ERK的

  3. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  4. The amount of citrullinated proteins in synovial tissue is related to serum anti-cyclic citrullinated peptide (anti-CCP) antibody levels.

    Science.gov (United States)

    Olivares-Martínez, Elizabeth; Hernández-Ramírez, Diego F; Núñez-Álvarez, Carlos A; Cabral, Antonio R; Llorente, Luis

    2016-01-01

    The objective of this study was to determine the relationship between citrullinated proteins in synovial tissue with peripheral anti-citrullinated peptides autoantibodies (ACPA) and peptidylarginine deiminase (PADI) PADI2, PADI3, and PADI4 messenger RNA (mRNA) expressions in synovial tissue and fibroblast-like synoviocytes in rheumatoid arthritis (RA) patients. Eleven RA and 12 osteoarthritis (OA) patients who underwent knee replacement surgery were studied. We detected citrullinated proteins in synovial tissue homogenates by western blot and serum ACPA by ELISA to anti-cyclic citrullinated peptide (anti-CCP) antibodies, and PADI2, PADI3, and PADI4 mRNA expressions in synovial tissue and in fibroblast-like synoviocytes. Patients with high amount of citrullinated proteins in synovial tissue (3 out of 7) have high levels of anti-CCP in serum. However, in the remaining 4 patients, the amount of synovial citrullinated proteins was minimal and their sera showed low levels of anti-CCP antibodies. Furthermore, we observed an increase in PADI2 mRNA expression in RA synovial tissue compared with OA patients (p = 0.02). We detected PADI3 mRNA in the synovial tissue of RA patients, but not in the tissue of OA patients. Even though fibroblast-type synoviocytes in RA are not the main source of PADs in the synovial tissue, they express PADI2 mRNA moderately, PADI4 mRNA weakly, while there is no detectable expression of PADI3 mRNA. In conclusion, we found a variety of citrullinated proteins in the synovial tissue of RA patients and the amount of such proteins is related to serum concentration of anti-CCP antibodies. We identified the presence of PADI3 mRNA expression in synovial tissue and PADI2 and PADI4 mRNA expressions in fibroblast-like synoviocytes from patients with RA.

  5. Arthritis of the hand - Rheumatoid

    Science.gov (United States)

    ... Media Find a Hand Surgeon Home Anatomy Rheumatoid Arthritis Email to a friend * required fields From * To * DESCRIPTION In its most literal sense, arthritis means “inflamed joint.” Arthritis describes any condition where ...

  6. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Corner / Patient Webcasts / Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos was designed to help you learn more about Rheumatoid Arthritis (RA). You will learn how the diagnosis of ...

  7. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... is Happening to the Joints? Rheumatoid Arthritis: Gaining Control – Working with your Rheumatologist Rheumatoid Arthritis: Additional Conditions Rheumatoid Arthritis: The Immune System Don’t have SilverLight? Get it here. A ...

  8. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... for Patients Arthritis Drug Information Sheets Benefits and Risks of Opioids in Arthritis ... within the Johns Hopkins Arthritis Center website is intended for educational purposes only. Physicians and other health care professionals ...

  9. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult Patients with Arthritis Complementary and Alternative Medicine for ... Patient Update Transitioning the JRA Patient to an Adult Rheumatologist Drug Information for Patients Arthritis Drug Information ...

  10. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ... Sheets Benefits and Risks of Opioids in Arthritis Management How to Give a Subcutaneous Injection Connect With ...

  11. 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.

  12. 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

  13. Anti-inflammatory effects of N-acylethanolamines in rheumatoid arthritis synovial cells are mediated by TRPV1 and TRPA1 in a COX-2 dependent manner.

    Science.gov (United States)

    Lowin, Torsten; Apitz, Martin; Anders, Sven; Straub, Rainer H

    2015-11-14

    The endocannabinoid system modulates function of immune cells and mesenchymal cells such as fibroblasts, which contribute to cartilage destruction in rheumatoid arthritis (RA). The aim of the study was to determine the influence of N-acylethanolamines anandamide (AEA), palmitoylethanolamine (PEA) and oleylethanolamine (OEA) on several features of arthritic inflammation in vitro (human material) and in vivo (a mouse model). Immunofluorescence and western blotting were used to detect cannabinoid receptors and related enzymes. Cytokines and MMP-3 were measured by ELISA. Intracellular signaling proteins were detected by proteome profiling. Proliferation was quantified by CTB reagent. Adhesion was assessed by the xCELLigence system. After onset of collagen type II arthritis, mice were treated daily with the FAAH inhibitor JNJ1661010 (20 mg/kg) or vehicle. IL-6, IL-8 and MMP-3 (determined only in synovial fibroblasts (SFs)) were downregulated in primary synoviocytes and SFs of RA and OA after AEA, PEA and OEA treatment. In SFs, this was due to activation of TRPV1 and TRPA1 in a COX-2-dependent fashion. FAAH inhibition increased the efficacy of AEA in primary synoviocytes but not in SFs. The effects of OEA and PEA on SFs were diminished by FAAH inhibition. Adhesion to fibronectin was increased in a CB1-dependent manner by AEA in OASFs. Furthermore, elevation of endocannabinoids ameliorated collagen-induced arthritis in mice. N-acylethanolamines exert anti-inflammatory effects in SFs. A dual FAAH/COX-2 inhibitor, increasing N-acylethanolamine levels with concomitant TRP channel desensitization, might be a good candidate to inhibit the production of proinflammatory mediators of synovial cells and to reduce erosions.

  14. 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...

  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. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Spondylitis News Osteoarthritis News Gout News Osteoporosis News Lupus News Fibromyalgia News Patient Corner Arthritis Drug Information Sheets Managing Your Arthritis Educational Videos for Patients ...

  17. Ultrasound in Arthritis.

    Science.gov (United States)

    Sudoł-Szopińska, Iwona; Schueller-Weidekamm, Claudia; Plagou, Athena; Teh, James

    2017-09-01

    Ultrasound is currently performed in everyday rheumatologic practice. It is used for early diagnosis, to monitor treatment results, and to diagnose remission. The spectrum of pathologies seen in arthritis with ultrasound includes early inflammatory features and associated complications. This article discusses the spectrum of ultrasound features of arthritides seen in rheumatoid arthritis and other connective tissue diseases in adults, such as Sjögren syndrome, lupus erythematosus, dermatomyositis, polymyositis, and juvenile idiopathic arthritis. Ultrasound findings in spondyloarthritis, osteoarthritis, and crystal-induced diseases are presented. Ultrasound-guided interventions in patients with arthritis are listed, and the advantages and disadvantages of ultrasound are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. 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.

  19. Arthritis and Veterans

    Centers for Disease Control (CDC) Podcasts

    2015-11-09

    One in three veterans has arthritis. This podcast provides information on how veterans can improve their quality of life with physical activity and other arthritis management strategies.  Created: 11/9/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 11/9/2015.

  20. What Is Rheumatoid Arthritis?

    Science.gov (United States)

    ... in Chinese 繁體中文 ) What Is Rheumatoid Arthritis? (in Korean 한국어 ) What Is Rheumatoid Arthritis? (in Vietnamese bằng ... his or her own body tissues. Researchers are learning many things about why and how this happens. ...

  1. Juvenile idiopathic arthritis

    NARCIS (Netherlands)

    Prakken, Berent; Albani, Salvatore; Martini, Alberto

    2011-01-01

    Juvenile idiopathic arthritis is a heterogeneous group of diseases characterised by arthritis of unknown origin with onset before age of 16 years. Pivotal studies in the past 5 years have led to substantial progress in various areas, ranging from disease classification to new treatments. Gene expres

  2. 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.

  3. 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 seroprevalence, 90.7%) for presenting uni- or bilateral chronic arthritis in the carpal joint. A complete study was performed, including symptomatology, histopathology, immunocytochemistry, immunohistochemistry, in situ hybridization, and microbiology. The carpus was the joint almost exclusively affected, with 10 sheep (76%) showing a moderate increase in carpal joint size (diameter range, 18-20 cm; normal range, 15-16 cm) without signs of locomotion problems and with 3 ewes (23%) showing severe inflammation with marked increase in diameter (21-24 cm), pain at palpation, and abnormal standing position. Grossly, chronic proliferative arthritis was observed in affected joints characterized by an increased thickness of the synovial capsule and synovial membrane proliferation. Microscopically, synovial membrane inflammation and proliferation and hyperplasia of synoviocytes were observed. More positive cases of SLRV infection were detected by immunocytochemistry of articular fluid than of bronchoalveolar lavage fluid. Immunohistochemistry and in situ hybridization also detected positive cells in the subsynovial connective tissue, lung, mediastinal lymph node, mammary gland, and mammary lymph node. All animals were negative for the presence of Mycoplasma or other bacteria in the articular space. The present outbreak likely represents an adaptation of a caprine virus to sheep. Our results underline the importance of the arthritis induced by SRLV in sheep, a clinical form that might be underestimated.

  4. Cardiovascular comorbidity in rheumatoid arthritis

    OpenAIRE

    Holmqvist, Marie E

    2010-01-01

    This thesis is based on four different studies, all focusing on co-morbidities in rheumatoid arthritis. Diabetes mellitus is assessed as a risk factor for rheumatoid arthritis, the temporal relationship between ischemic heart disease and rheumatoid arthritis, and the extent of coronary stenosis in rheumatoid arthritis, is studied. The rationale for this is that patients with rheumatoid arthritis suffer an increased risk of ischemic heart disease that cannot be explained by traditional risk fa...

  5. Therapeutic effect of Captopril on rheumatoid arthritis in rats

    Institute of Scientific and Technical Information of China (English)

    Hong-Mei Liu; Kai-Jie Wang

    2014-01-01

    Objective:To investigate the therapeutic effect of the intervention treatment with different doses ofCaptopril onTNF-αcontents in serum of rheumatoid arthritis(RA) rats, and to provide the theoretical proofs for clinical application ofCaptopril in treatments of rheumatoid diseases. Methods:FiftyWistar rats were randomly divided into5 groups, namely,GroupA,GroupB, GroupC,GroupD,GroupE with10 ratsin each group.Injection ofFreund’s complete adjuvant was employed to establish adjuvant-induced arthritis model in rats.GroupA was model group; after model establishment, rats were treated with20 mL normal saline as placebo(ip.).Rats inGroupB were treated with8 mg/kg cyclophosphamide(ip.).Rats inGroupC,D andE were intraperitoneally injected with30 mg/kg,100 mg/kg and300 mg/kgCaptopril respectively.Rats in each group were subjected to continuous treatment for3 weeks, and then sacrificed.Eyeballs of rats were excised and blood was collected.TNF-αcontent in serum were detected usingELISA; each group rats were compared for the hind legs arthrocele.Right ankle tissues of rats were collected to prepare section, and microscopic observation of pathological changes was performed. Results:TNF-αcontent in serum ofGroupA rats was significantly higher than that of rats in other4 groups(P0.05).FromDay8, ankle arthrocele of rats inGroupsB,C,D andE was obviously relieved compared with that ofGroupA rats; the anti-inflammatory effects were gradually enhanced with the extension of medication time.Treatments ofGroupsC,D andE showed significant activities against tardive arthrocele; the degree of ankle arthrocele in rats of these three groups was lower than that ofGroupA rats(P<0.01).Histological observation showed that large amount of inflammatory cells and plasmocyte infiltration was found in ankle synovial tissues ofGroupA rats.Relief of hyperaemia and edema of right ankle synovial tissues as well as significant decrease in synoviocyte layer hyperplasia, intra-articular inflammatory

  6. [Septic arthritis and spondylitis].

    Science.gov (United States)

    Fujikawa, Yosuke

    2014-10-01

    Septic arthritis and spondylitis in elderly adult are uncommon disease. But symptoms and signs of septic arthritis and spondylitis are an important medical emergency, with high mortality and morbidity. Delayed or inadequate treatment can result in irreversible joint destruction and neurological condition. Early diagnoses as well as prompt and effective treatment are essential for avoiding severe outcomes. In spite of advances in diagnostic imaging techniques, the incidence of septic arthritis and spondylitis appears to have been increased. The aging of the population, the widespread use of immunosuppressant therapies, including systemic corticosteroids, cytokines and anticytokines, and growing resistance to conventional antibiotics seem to be the major cause.

  7. Juvenile chronic arthritis.

    Science.gov (United States)

    Southwood, T R; Woo, P

    1995-05-01

    The nomenclature and classification criteria for arthritis in children should be dealt with initially as separate issues, although they are undoubtedly intertwined. The classification criteria should aim to delineate homogeneous patient populations, yet should be flexible enough to incorporate advances in disease knowledge. It should be recognized that arriving at an international consensus for classification criteria will merely provide a set of operational definitions to facilitate research, and not a set of diagnostic criteria. Indeed the only point to obtaining consensus is to begin a process of systematic ongoing review of the criteria. The labels attached to any of these diseases should facilitate accurate communication. In view of the heterogeneous nature of childhood arthritis, consideration should be given to using a broad umbrella term such as juvenile or childhood arthritis only for communicating with the lay public. Medical nomenclature should be formulated to reflect accurately homogeneous subgroups of arthritis, and should not artificially proscribe a relationship between paediatric and adult disease.

  8. Arthritis in Children

    Science.gov (United States)

    ... Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial ... Content Article Body Arthritis is an inflammation of the joints that produces swelling, redness, heat, and pain. Although it is typically thought of as a ...

  9. Arthritis and IBD

    Science.gov (United States)

    ... pain and stiffness in the lower spine and sacroiliac joints (at the bottom of the back). Interestingly, and ... addition to causing arthritis of the spine and sacroiliac joints, ankylosing spondylitis can cause inflammation of the eyes, ...

  10. Oral and nasal administration of chicken type Ⅱ collagen suppresses adjuvant arthritis in rats with intestinal lesions induced by meloxicam

    Institute of Scientific and Technical Information of China (English)

    Yong-Qiu Zheng; Wei Wei; Yu-Xian Shen; Min Dai; Li-Hua Liu

    2004-01-01

    AIM: To investigate the curative effects of oral and nasal administration of chicken type Ⅱ collagen (CⅡ) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions.METHODS: AA model in Sprague-Dawley (SD) rats with or without intestinal lesions induced by meloxicam was established and those rats were divided randomly into six groups which included AA model, AA model+meloxicam,AA model+oral CⅡ, AA model+nasal CⅡ, AA model+meloxicam+oral CⅡ and AA model+meloxicam+nasal CⅡ (n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund's adjuvant (CFA), and then treated with chicken CⅡ intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT)method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis.RESULTS: Intragastrical administration of meloxicam (1.5 mg/kg) induced multiple intestinal lesions in AA rats.There was a significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01) and AA model group (P<0.01) compared with normal group. DAO activities of intestinal homogenates in AA+meloxicam group were significantly less than those in AA rats (P<0.01). There was a significant increase of intestinal MPO activities in AA+meloxicam group compared with normal control (P<0.01). Oral or nasal administration of CⅡ (20 μg/kg)could suppress the secondary hind paw swelling(P<0.05for oral CⅡ; P<0.01 for nasal CⅡ), synoviocyte proliferation (P<0.01) and histopathological degradation in AA rats, but they had no significant effects on DAO and MPO changes.However, oral administration of CⅡ (20 μg/kg) showed the limited efficacy on arthritis

  11. Understanding Rheumatoid Arthritis (RA): Research

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Research Past Issues / Summer 2014 Table of ... project plan to address relevant challenges for rheumatoid arthritis. Read Part 1 on Lupus in MedlinePlus magazine, ...

  12. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... any advice you receive from your rheumatologist. Click A Link Below To Play Rheumatoid Arthritis: Symptoms and ... About Victoria Ruffing, RN Ms. Ruffing has been a member of the Arthritis Center since 2000, currently ...

  13. Handout on Health: Rheumatoid Arthritis

    Science.gov (United States)

    ... that are prone to fracture). Like many other rheumatic diseases, rheumatoid arthritis is an autoimmune disease ( auto means self), so ... arthritis than men. The disease may improve during pregnancy and flare after pregnancy. Breastfeeding may also aggravate ...

  14. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis Vital Education Initiative Rheumatology Conference Rheumatology Rounds Case Rounds Radiology Rounds Pathophysiology of the Rheumatic Diseases Our Research Patient-Centered Outcomes Research Research Studies The Camille Julia Morgan Arthritis Research and Education ...

  15. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Ruffing has been a member of the Arthritis Center since 2000, currently serving as the Nurse Manager. She is a critical ... Management for Rheumatoid Arthritis Patients Rehabilitation of Older ...

  16. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Adult Rheumatologist Drug Information for Patients Arthritis Drug Information Sheets Benefits and Risks of Opioids in Arthritis Management How to Give a Subcutaneous Injection Connect With ...

  17. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Spondylitis News Osteoarthritis News Gout News Osteoporosis News Lupus News Fibromyalgia News Patient Corner Arthritis Drug Information ... Connect With Us Johns Hopkins Rheumatology Arthritis Center Lupus Center Lyme Disease Clinical Research Center Myositis Center ...

  18. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Spondylitis News Osteoarthritis News Gout News Osteoporosis News Lupus News Fibromyalgia News Patient Corner Arthritis Drug Information ... Connect With Us Johns Hopkins Rheumatology Arthritis Center Lupus Center Lyme Disease Clinical Research Center Myositis Center ...

  19. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... are available, what is happening in the immune system and what other conditions are associated with RA. ... Rheumatoid Arthritis: Additional Conditions Rheumatoid Arthritis: The Immune System Don’t have SilverLight? Get it here. A ...

  20. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis 101 2010 E.S.C.A.P.E. Study Patient Update Transitioning the JRA Patient to an Adult Rheumatologist Drug Information for Patients Arthritis Drug Information Sheets Benefits and Risks of Opioids in Arthritis Management How ...

  1. Th17 cytokines and arthritis

    NARCIS (Netherlands)

    E.W. Lubberts (Erik)

    2010-01-01

    textabstractTh17 cells are implicated in human autoimmune diseases, such as rheumatoid arthritis (RA), although it has not been established whether this persistent destructive arthritis is driven by Th1 and/or Th17 cells. Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis as has b

  2. [Juvenile idiopathic arthritis].

    Science.gov (United States)

    Herlin, Troels

    2002-08-19

    The new classification of juvenile idiopathic arthritis (JIA) is described in this review. Clinical characteristics divide JIA in to subtypes: systemic, oligoarticular (persistent and extended type), RF-positive and--negative polyarticular, enthesitis-related arthritis and psoriatic arthritis. In addition to the clinical characteristics, genetic and biochemical differences suggest that JIA could be regarded as a general term covering various diseases. Complications described are uveitis, temporomandibular joint affection and growth disturbances. The therapeutic strategy should be planned individually according to age, subtype and disease activity and carried out as teamwork with several specialties. Drugs showing significant effectiveness in controlled studies are primarily methotrexate and sulphasalazine. An immunomodulating agent, etanercept, a soluble TNF alpha-receptor fusion protein, has shown a promising effect in severe polyarticular JIA refractory to methotrexate treatment.

  3. Dermatoglyphics in rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Ravindranath R

    2003-10-01

    Full Text Available Patients with rheumatoid arthritis have been referred to Division of Human Genetics for counselling. Qualitative dermatoglyphics comprising of finger print pattern, interdigital pattern, hypothenar pattern and palmar crease were studied on 26 female and 11 male rheumatoid arthritis patients. Comparison between patient male and control male; and patient female and control female has been done. ′Chi′ square test was performed. In male patients, with hands together, arches were increased, loops/ whorls were decreased. Partial Simian crease was significantly increased. In the right hand, patterns were increased in the 3rd interdigital area. On the other hand, in female patients there was a significant increase in whorls and decrease in loops on the first finger on both the hands, increase in arches on the 3rd finger; both arches and whorls on the 4th finger of left hand. Present study has emphasized that dermatoglyphics could be applied as a diagnostic tool to patients with rheumatoid arthritis.

  4. [Arthritis and clinical history].

    Science.gov (United States)

    Silva, Lígia; Sampaio, Luzia; Pinto, José; Ventura, Francisco S

    2011-01-01

    In front of a patient with arthritis, clinical good-sense tells that the most probable diagnosis are the most prevalent ones. Nevertheless, we have to exclude a multiplicity of other aetiologies, less frequent, but with highest implications in the therapeutic conduct. Infections by Brucella and by Borrelia are rare causes of chronic arthritis, yet are diagnosis to consider, even when the clinical manifestations aren't the most typical, as there still exist endemic areas in Portugal. Here we report two clinical cases about patients with arthritis for more than one year, subject to ineffective exams ant treatments. Only the clinical history could put on evidence clinical-epidemiological data, suggestive of Brucellosis and Lyme Disease, namely the professional contact with infected animals, and the history of probable erythema migrans, that pointed toward the correct diagnosis. So, with directed therapeutic, there was complete resolution of the inflammatory symptoms.

  5. Targeting non-canonical nuclear factor-κB signalling attenuates neovascularization in a novel 3D model of rheumatoid arthritis synovial angiogenesis.

    Science.gov (United States)

    Maracle, Chrissta X; Kucharzewska, Paulina; Helder, Boy; van der Horst, Corine; Correa de Sampaio, Pedro; Noort, Ae-Ri; van Zoest, Katinka; Griffioen, Arjan W; Olsson, Henric; Tas, Sander W

    2017-02-01

    Angiogenesis is crucial in RA disease progression. Lymphotoxin β receptor (LTβR)-induced activation of the non-canonical nuclear factor-κB (NF-κB) pathway via NF-κB-inducing kinase (NIK) has been implicated in this process. Consequently, inhibition of this pathway may hold therapeutic potential in RA. We describe a novel three-dimensional (3D) model of synovial angiogenesis incorporating endothelial cells (ECs), RA fibroblast-like synoviocytes (RAFLSs) and RA synovial fluid (RASF) to further investigate the contributions of NF-κB in this process. Spheroids consisting of RAFLSs and ECs were stimulated with RASF, the LTβR ligands LTβ and LIGHT, or growth factor bFGF and VEGF, followed by quantification of EC sprouting using confocal microscopy and digital image analysis. Next, the effects of anginex, NIK-targeting siRNA (siNIK), LTβR-Ig fusion protein (baminercept) and a novel pharmacological NIK inhibitor were investigated. RASF significantly promoted sprout formation, which was blocked by the established angiogenesis inhibitor anginex (P factors (P model of synovial angiogenesis incorporating RAFLSs, ECs and RASF that mimics the in vivo situation. Using this system, we demonstrate that non-canonical NF-κB signalling promotes neovascularization and show that this model is useful for dissecting relative contributions of signalling pathways in specific cell types to angiogenic responses and for testing pharmacological inhibitors of angiogenesis. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Neonatal Candida arthritis

    Directory of Open Access Journals (Sweden)

    Saurabh Sharma

    2014-01-01

    Full Text Available Fungal arthritis is an uncommon yet serious disorder in the newborn. Delay in diagnosis and management can lead to significant morbidity. We report our experience with management of two such cases. Two preterm neonates with multifocal arthritis caused by Candida were studied. Diagnosis was made by clinical examination, laboratory investigations, radiological investigations and culture. Both were treated by aspiration, arthrotomy and antifungal therapy. One patient recovered fully from the infection while the other had growth disturbances resulting in limb length inequality at recent followup. Prompt and expeditious evacuation of pus from joints and antifungal therapy is imperative for treatment. Associated osteomyelitis leads to further difficulty in treatment.

  7. Psoriatic Arthritis Registries.

    Science.gov (United States)

    Sarzi-Puttini, Piercarlo; Varisco, Valentina; Ditto, Maria Chiara; Benucci, Maurizio; Atzeni, Fabiola

    2015-11-01

    The introduction of new biological drugs for the treatment of rheumatoid arthritis and spondyloarthritis has led to the creation of a number of registries in Europe and the United States. Most of them are sponsored by national rheumatology societies, and provide information that is useful in clinical practice concerning the clinical characteristics, efficacy, and safety of all licensed biological drugs. Their findings also help to improve our understanding of the quality of life and working ability of patients receiving biological drugs, and suggest methods for allocating resources. However, there are only a few registries for psoriatic arthritis, and efforts should be made to increase their number to obtain further reliable and useful data.

  8. Vasculitis and inflammatory arthritis.

    Science.gov (United States)

    Watts, Richard A; Scott, David G I

    2016-10-01

    Vasculitis has been described in most types of inflammatory arthritis. The best described and most widely recognised form is rheumatoid vasculitis. The incidence of systemic rheumatoid vasculitis has declined significantly following the general early use of methotrexate in the 1990s, and it is now a rare form of vasculitis. Treatment of rheumatoid vasculitis is conventionally with glucocorticoids and cyclophosphamide, but there is an increasing role for rituximab similar to that in other types of vasculitis. Despite these developments the mortality of rheumatoid vasculitis remains high. Vasculitis in other types of inflammatory arthritis is less well described and the treatment remains empirical. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Arthritis Pain Reliever

    Centers for Disease Control (CDC) Podcasts

    2011-12-27

    Learn more about the benefits of physical activity and the types and amounts of exercise helpful for people with arthritis.  Created: 12/27/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 12/27/2011.

  10. Monitoring rheumatoid arthritis

    NARCIS (Netherlands)

    Gvozdenovic, Emilia

    2016-01-01

    In this thesis we focussed on so-called ‘treat to target’ therapy in rheumatoid arthritis (RA). Treat to target relies on repetitive measurements of disease activity using a composite score that incorporates signs of disease activity such as laboratory results, findings of physical joint assessments

  11. Juvenile arthritis and uveitis.

    Science.gov (United States)

    Kanski, J J

    1990-01-01

    The association between juvenile arthritis and uveitis is reviewed. Some children with the HLA-B27 related spondyloarthropathies develop anterior uveitis. About 20% of patients with juvenile rheumatoid arthritis (JRA) who are negative for IgM rheumatoid factor develop a frequently bilateral, nongranulomatous chronic anterior uveitis. Risk factors for uveitis in JRA patients are: female gender, pauciarticular onset of arthritis, presence of circulating antinuclear antibodies, and the antigens HLA-DW5 and HLA-DPw2. Uveitis is rare after seven years or more have elapsed from the onset of arthritis. The visual prognosis in patients with uveitis is good in 25% and fair in 50%. The remaining 25% develop visual impairment from complicated cataract and/or secondary inflammatory glaucoma. The potential benefit of cytotoxic agents in the treatment of intractable uveitis is outweighed by the risk of serious side effects. The management of secondary inflammatory glaucoma is unsatisfactory, but the results of treatment of complicated cataracts by lensectomy-vitrectomy are good.

  12. Neonatal septic arthritis.

    Science.gov (United States)

    Halder, D; Seng, Q B; Malik, A S; Choo, K E

    1996-09-01

    Neonatal septic arthritis has always been considered as separate from its counterpart in older children. The condition is uncommon but serious. Affected neonates usually survive, but with permanent skeletal deformities. Ten cases of neonatal septic arthritis were diagnosed between January 1989 and December 1993 in the neonatal intensive care units of two referral hospitals in the state of Kelantan, Malaysia. All except one neonate was born prematurely. The mean age of presentation was 15.6 days. Joint swelling (10/10), increased warmth (7/10) and erythema of the overlying skin (7/10) were the common presenting signs. Vague constitutional symptoms preceded the definitive signs of septic arthritis in all cases. The total white cell counts were raised with shift to the left. The knee (60%) was not commonly affected, followed by the hip (13%) and ankle (13%). Three neonates had multiple joint involvement. Coexistence of arthritis with osteomyelitis was observed in seven neonates. The commonest organism isolated was methicillin resistant Staphylococcus aureus (9/10). Needle aspiration was performed in nine neonates and one had incision with drainage. Follow up data was available for five neonates and two of these had skeletal morbidity. Early diagnosis by frequent examination of the joints, prompt treatment and control of nosocomial infection are important for management.

  13. IMAGING OF PSORIATIC ARTHRITIS

    Directory of Open Access Journals (Sweden)

    S. D'Angelo

    2011-09-01

    Full Text Available Imaging of psoriatic arthritis (PsA is important for two reasons: the differential diagnosis from other arthritides and the assessment of structural damage that can be inhibited by the new drugs such as the anti-TNFα agents. Plain film radiographic findings of peripheral arthritis have been important in elaborating the concept of PsA as a separate disease entity. Characteristic aspects of psoriatic peripheral arthritis help the differentiation from rheumatoid arthritis. High-resolution ultrasonography (US, US combined with power Doppler (PDUS and magnetic resonance imaging (MRI can be used to image joint synovitis of PsA. Radiologic features of spondylitis associated with psoriasis are similar to spondylitis associated with reactive arthritis and differ from those of primary ankylosing spondylitis (AS and the spondylitis associated with inflammatory bowel disease. MRI is very sensitive for the early diagnosis of sacroiliitis. There have been no MRI studies on the spine of patients with PsA. In primary AS bone oedema in the vertebral bodies is an indicator of active disease and can ameliorate during anti-TNFα therapy. Historically, plain film radiography have played a pivotal role in defining enthesitis lesions of SpA. However, entheseal bone changes appear late. US and MRI have proved to be a highly sensitive and non invasive tools. Recent US and MRI studies on both finger and toe dactylitis have established that dactylitis is due to flexor tenosynovitis and marked adjacent soft tissue swelling with a variable degree of small joint synovitis. There is no evidence of enthesitis of the insertion of the flexor digitorum tendons and of the attachment of the caspsule of the digit joints. Key words: Enthesitis, dactylitis, spondyloarthritis, ultrasound, magnetic resonance, imaging

  14. Anti-inflammatory effects of sphingosine kinase modulation in inflammatory arthritis.

    Science.gov (United States)

    Lai, Wen-Qi; Irwan, Anastasia Windy; Goh, Hong Heng; Howe, Hwee Siew; Yu, David T; Valle-Oñate, Rafael; McInnes, Iain B; Melendez, Alirio J; Leung, Bernard P

    2008-12-01

    Sphingosine kinase (SphK) is a key enzyme in the sphingolipid metabolic pathway responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P). SphK/S1P play a critical role in angiogenesis, inflammation, and various pathologic conditions. Recently, S1P(1) receptor was found to be expressed in rheumatoid arthritis (RA) synovium, and S1P signaling via S1P(1) enhances synoviocyte proliferation, COX-2 expression, and prostaglandin E(2) production. Here, we examined the role of SphK/S1P in RA using a potent SphK inhibitor, N,N-dimethylsphingosine (DMS), and a molecular approach against one of its isoenzymes, SphK1. We observed that levels of S1P in the synovial fluid of RA patients were significantly higher than those of osteoarthritis patients. Additionally, DMS significantly reduced the levels of TNF-alpha, IL-6, IL-1beta, MCP-1, and MMP-9 in cell-contact assays using both Jurkat-U937 cells and RA PBMCs. In a murine collagen-induced arthritis model, i.p. administration of DMS significantly inhibited disease severity and reduced articular inflammation and joint destruction. Treatment of DMS also down-regulated serum levels IL-6, TNF-alpha, IFN-gamma, S1P, and IgG1 and IgG2a anti-collagen Ab. Furthermore, DMS-treated mice also displayed suppressed proinflammatory cytokine production in response to type II collagen in vitro. Moreover, similar reduction in incidence and disease activity was observed in mice treated with SphK1 knock-down via small interfering RNA approach. Together, these results demonstrate SphK modulation may provide a novel approach in treating chronic autoimmune conditions such as RA by inhibiting the release of pro-inflammatory cytokines.

  15. Genetics Home Reference: juvenile idiopathic arthritis

    Science.gov (United States)

    ... Home Health Conditions juvenile idiopathic arthritis juvenile idiopathic arthritis Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Juvenile idiopathic arthritis refers to a group of conditions involving joint ...

  16. Rheumatoid Arthritis: Can It Affect the Eyes?

    Science.gov (United States)

    ... arthritis: Can it affect the eyes? Can rheumatoid arthritis affect the eyes? Answers from April Chang-Miller, M.D. Rheumatoid arthritis is a chronic inflammatory disease that primarily affects ...

  17. Rheumatoid Arthritis and Complementary Health Approaches

    Science.gov (United States)

    ... T U V W X Y Z Rheumatoid Arthritis: In Depth Share: On This Page Key Points ... help ensure coordinated and safe care. About Rheumatoid Arthritis Rheumatoid arthritis is an inflammatory autoimmune disease—a ...

  18. Accommodation and Compliance Series: Employees with Arthritis

    Science.gov (United States)

    ... Resources Home | Accommodation and Compliance Series: Employees with Arthritis By Beth Loy, Ph.D. Preface Introduction Information ... SOAR) at http://AskJAN.org/soar . Information about Arthritis How prevalent is arthritis? An estimated 50 million ...

  19. Rheumatoid Arthritis: Can It Affect the Lungs?

    Science.gov (United States)

    ... arthritis: Can it affect the lungs? Can rheumatoid arthritis affect your lungs? Answers from April Chang-Miller, M.D. Although rheumatoid arthritis primarily affects joints, it sometimes causes lung disease ...

  20. Clinical management of septic arthritis.

    Science.gov (United States)

    Sharff, Katie A; Richards, Eric P; Townes, John M

    2013-06-01

    Septic arthritis is a rheumatologic emergency as joint destruction occurs rapidly and can lead to significant morbidity and mortality. Accurate diagnosis can be particularly challenging in patients with underlying inflammatory joint disease. This review outlines the risk factors for septic arthritis and summarizes the causative bacterial organisms. We highlight advances in antibiotic management with a focus on new drugs for methicillin-resistant Staphylococcus aureus (MRSA) and discuss the use of adjunctive therapies for treatment of septic arthritis in adults.

  1. [Sport and rheumatoid arthritis].

    Science.gov (United States)

    Proschek, D; Rehart, S

    2014-06-01

    Sport is becoming increasingly more important in our society. Due to the changing age spectrum with a greater number of elderly and substantially more active people, an increasing number of people with underlying orthopedic diseases are becoming interested in participating in sport. This article deals with the possibilities and effects of sporting activities for people with rheumatoid arthritis within the framework of a conservative therapy. A literature search was carried out using medical search engines, in particular PubMed, and also via the recommendations of specialist societies and patient help groups. The quality of life of patients with rheumatoid arthritis consists of physical, mental and social components. Sport as a means of rehabilitation influences all of these components. Sport should be comprehended as a form of therapy and be adapted to the needs of the individual patient. The willingness to actively participate in sport should always be highly rated and encouraged. Sport is therefore an important pillar of therapy in a conservative total concept. The main aspects of sport therapeutic activities are functional, pedagogical and experience-oriented aspects. The clinical symptoms, extent of damage and physical impairment must, however, be evaluated and taken into consideration for the therapeutic concept. The amount of data on the complex topic of sport and rheumatoid arthritis is low and is mainly dealt with as retrospective reviews. A prospective randomized study basis is lacking. The aim must therefore be to confirm the currently available recommendations for various types of sport in controlled studies.

  2. Imaging of Posttraumatic Arthritis, Avascular Necrosis, Septic Arthritis, Complex Regional Pain Syndrome, and Cancer Mimicking Arthritis.

    Science.gov (United States)

    Rupasov, Andrey; Cain, Usa; Montoya, Simone; Blickman, Johan G

    2017-09-01

    This article focuses on the imaging of 5 discrete entities with a common end result of disability: posttraumatic arthritis, a common form of secondary osteoarthritis that results from a prior insult to the joint; avascular necrosis, a disease of impaired osseous blood flow, leading to cellular death and subsequent osseous collapse; septic arthritis, an infectious process leading to destructive changes within the joint; complex regional pain syndrome, a chronic limb-confined painful condition arising after injury; and cases of cancer mimicking arthritis, in which the initial findings seem to represent arthritis, despite a more insidious cause. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Septic arthritis in adult horses.

    Science.gov (United States)

    Carstanjen, B; Boehart, S; Cislakova, M

    2010-01-01

    Septic arthritis in horses is a serious disease which can become life-threatening. In case the infection can be eliminated before irreversible joint damage occurs, complete recovery is possible. This article gives an overview of the literature concerning etiology, diagnosis and strategies of therapy in cases of septic arthritis in adult horses, with special reference to novel options of treatment.

  4. Mouse Models of Rheumatoid Arthritis.

    Science.gov (United States)

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.

  5. Occupational therapy for rheumatoid arthritis.

    NARCIS (Netherlands)

    Steultjens, E.M.J.; Dekker, J.; Bouter, L.M.; Schaardenburg, D.J. van; Kuyk, M.A.H. van; Ende, C.H.M. van den

    2004-01-01

    Background: For persons with rheumatoid arthritis (RA) the physical, personal, familial, social and vocational consequences are extensive. Occupational therapy (OT), with the aim to facilitate task performance and to decrease the consequences of rheumatoid arthritis for daily life activities, is con

  6. Kartagener syndrome and rheumatoid arthritis.

    Science.gov (United States)

    Rébora, Martin Esteban; Cuneo, Julia Ana; Marcos, Josefina; Marcos, Juan Carlos

    2006-02-01

    We report the case of a 38-year-old female patient, affected with Kartagener syndrome (primary ciliary dyskinesia), who developed seropositive and erosive rheumatoid arthritis. According to our review, there are only 6 cases reported so far with this association without a definite etiopathogenic linkage recognized in common. Chronic infections resulting from the ciliary dysfunction might be a trigger for rheumatoid arthritis.

  7. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Sheets Benefits and Risks of Opioids in Arthritis Management How to Give a Subcutaneous Injection Connect With Us Johns Hopkins Rheumatology Arthritis Center Lupus Center Lyme Disease Clinical Research Center Myositis Center Scleroderma Center Sjogren’s Syndrome Center ...

  8. Psoriatic arthritis as a mountain

    Directory of Open Access Journals (Sweden)

    J.M. Berthelot

    2011-09-01

    Full Text Available There is no doubt that inflammatory arthritis/enthesitis and psoriasis coexist more frequently than would be expected by chance: for instance, in a study of 1285 patients with psoriasis seen in an hospital, 483 (38% were suffering from arthritis/ enthesitis, including 40 patients classified as Rheumatoid Arthritis (RA (3%, 177 (14% as undifferentiated arthritis (UA, and 266 (21% as Psoriatic Arthritis (PsA (1. Although lower percentages have been noticed in the general population with psoriasis (6% of PsA in an extensive study of 1844 patients with psoriasis (2, they were superior to 5% (i.e. at least 5 times greater than the figures found for patients without psoriasis (3-7.

  9. Combination therapy for pain management in inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis)

    NARCIS (Netherlands)

    S. Ramiro; H. Radner; D. van der Heijde; A. van Tubergen; R. Buchbinder; D. Aletaha; R.B.M. Landewé

    2011-01-01

    Despite optimal therapy with disease-modifying antirheumatic drugs, many people with inflammatory arthritis (IA) continue to have persistent pain that may require additional therapy. To assess the benefits and safety of combination pain therapy for people with IA (rheumatoid arthritis (RA), ankylosi

  10. 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.

  11. Autoantibodies in inflammatory arthritis.

    Science.gov (United States)

    Conigliaro, P; Chimenti, M S; Triggianese, P; Sunzini, F; Novelli, L; Perricone, C; Perricone, R

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.

  12. 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.

  13. ERK信号转导通路与类风湿关节炎%ERK signaling pathway in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    王建竹; 孔祥英; 林娜

    2011-01-01

    The excessive activation of extracellular signal - regulated kinase( ERK ) signaling pathway, which is a significant feature of rheumatoid arthritic( RA ) arthropathy, plays an important role in the process of synoviocyte dysfunction and destruction of cartilage and bone.Understanding the pathomechanism of ERK signaling in RA provides a new target for developing new drug and therapeutic strategy.This review summarizes the current knowledge of the activation, regulation and function of ERK pathway, and also analyzes the role of this signaling transduction in the destruction of joints and the pathogenesis of RA.%@@ 丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)信号转导通路是细胞外信号引起细胞核内反应的重要通路,而细胞外信号调节激酶(extracellular signal-regulated kinase, ERK)通路是MAPKs家族中的重要成员,其异常活化与类风湿关节炎(rheumatoid arthritis,RA)关节破坏的病理过程密切相关.

  14. Proinflammatory Role of Vascular Endothelial Growth Factor in the Pathogenesis of Rheumatoid Arthritis: Prospects for Therapeutic Intervention

    Directory of Open Access Journals (Sweden)

    Seung-Ah Yoo

    2008-01-01

    Full Text Available Recent experimental and clinical studies have placed new emphasis on the role of angiogenesis in chronic inflammatory disease. Vascular endothelial growth factor (VEGF and its receptors are the best characterized system in the regulation of rheumatoid arthritis (RA by angiogenesis. Furthermore, in addition to its angiogenic role, VEGF can act as a direct proinflammatory mediator during the pathogenesis of RA, and protect rheumatoid synoviocytes from apoptosis, which contributes to synovial hyperplasia. Therefore, the developments of synovial inflammation, hyperplasia, and angiogenesis in the joints of RA patients seem to be regulated by a common cue, namely, VEGF. Agents that target VEGF, such as anti-VEGF antibody and aptamer, have yielded promising clinical data in patients with cancer or macular degeneration, and in RA patients, pharmacologic modulations targeting VEGF or its receptor may offer new therapeutic approaches. In this review, the authors integrate current knowledge of VEGF signaling and information on VEGF antagonists gleaned experimentally and place emphasis on the use of synthetic anti-VEGF hexapeptide to prevent VEGF interacting with its receptor.

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

    Science.gov (United States)

    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.

  16. APLAR rheumatoid arthritis treatment recommendations.

    Science.gov (United States)

    Lau, Chak Sing; Chia, Faith; Harrison, Andrew; Hsieh, Tsu-Yi; Jain, Rahul; Jung, Seung Min; Kishimoto, Mitsumasa; Kumar, Ashok; Leong, Khai Pang; Li, Zhanguo; Lichauco, Juan Javier; Louthrenoo, Worawit; Luo, Shue-Fen; Nash, Peter; Ng, Chin Teck; Park, Sung-Hwan; Suryana, Bagus Putu Putra; Suwannalai, Parawee; Wijaya, Linda Kurniaty; Yamamoto, Kazuhiko; Yang, Yue; Yeap, Swan Sim

    2015-09-01

    Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue. The AGREE II instrument and the ADAPTE Collaboration framework were applied to systematically identify, appraise, synthesize, and adapt international rheumatoid arthritis guidelines for use in the Asia-Pacific region. Forty rheumatoid arthritis treatment recommendations, based on evidence and expert opinion, were drafted and are presented in this report. The Asia Pacific of Associations for Rheumatology rheumatoid arthritis treatment recommendations are intended to serve as a reference for best practice management of rheumatoid arthritis in Asia-Pacific, focusing on local issues to ensure the delivery of basic care for these patients, and to improve their outcomes. In addition, the document will serve as a reference for national rheumatology associations in Asia-Pacific for developing guidelines in their respective countries. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  17. JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    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.

  18. Pain and microcrystalline arthritis

    Directory of Open Access Journals (Sweden)

    R. Ramonda

    2014-06-01

    Full Text Available Microcrystals are responsible for some of the most common and complex arthropathies which are often accompanied by intense, severe pain and inflammatory reactions. The main pathogens are crystals of monosodium urate (MSU, responsible for the gout, calcium pyrophosphate (CPP, which deposits also in various clinical forms of arthopathies, and basic calcium phosphate associated with osteoarthritis. In this context, the microcrystal arthritis is characterized by multiple, acute attacks followed by chronic pain, disability, impaired quality of life, and increased mortality. Given their chronic nature, they represent an ever more urgent public health problem. MSU and CPP crystals are also able to activate nociceptors. The pain in mycrocrystalline arthritis (MCA is an expression of the inflammatory process. In the course of these diseases there is an abundant release of inflammatory molecules, including prostaglandins 2 and kinins. Interleukin-1 represents the most important cytokine released during the crystal-induced inflammatory process. Therefore, clinically, pain is the most important component of MCA, which lead to functional impairment and disability in a large proportion of the population. It is fundamental to diagnose these diseases as early as possible, and to this aim, to identify appropriate and specific targets for a timely therapeutic intervention.

  19. Radiological aspects of rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Schacherl, M.

    1985-09-23

    An introductory summary of the imaging-diagnosis will be given. The necessity of acquiring a catalogue of application to particular imaging methods is emphasized. Discussion of step by step diagnosis regarding rheumatologic questions is given on example of the hand. Technically insufficient radiographs and bad habits during diagnostic analysis are pointed out. Radiologic problems in differentiating arthritis/osteoarthrosis will be mentioned. The discussion of these points is followed by outlining the radiology of rheumatoid arthritis and the complexity of this disease. Introduction of a new stage classification. Finally twelve basic radiologic types of rheumatoid arthritis will be presented.

  20. Promising Results for Drug to Fight Arthritis Linked to Psoriasis

    Science.gov (United States)

    ... Results for Drug to Fight Arthritis Linked to Psoriasis Psoriatic arthritis causes painful joint swelling, but new ... of a form of arthritis often linked to psoriasis. According to Stanford University researchers, psoriatic arthritis is ...

  1. Dermatitis herpetiformis and rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Singal Archana

    2002-01-01

    Full Text Available A 35- year-old deaf and dumb woman with clinical and histopothological diagnosis of dermatitis herpetiforrnis (DH is reported for its rare association with rheumatoid arthritis (PA.

  2. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... a Question Physician Corner Rheumatology Conference Rheumatology Rounds Case Rounds Radiology Rounds Pathophysiology of the Rheumatic Diseases Our Research Patient-Centered Outcomes Research Research Studies The Camille Julia Morgan Arthritis Research and Education ...

  3. Genetics Home Reference: rheumatoid arthritis

    Science.gov (United States)

    ... D; Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate; Wellcome Trust Case Control Consortium, Concannon P, Onengut-Gumuscu S, Rich SS, Deloukas P, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Ärlsetig L, Martin J, ...

  4. Therapy strategies in psoriatic arthritis.

    Science.gov (United States)

    Coates, Laura C

    2015-01-01

    Psoriatic arthritis (PsA) is a heterogeneous condition with a myriad of different clinical presentations. It commonly affects the skin and musculoskeletal system causing psoriasis, peripheral arthritis, axial arthritis, enthesitis and dactylitis. Many patients also have related conditions, such as those within the metabolic syndrome and associated spondyloarthritis (SpA) conditions including inflammatory bowel disease and uveitis. Any therapeutic strategy must be tailored to the individual patient, taking into account her/his complete clinical presentation and comorbidities. New treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) provide evidence based recommendations on effective therapies for the management of each different manifestation of PsA, and how treatment may be affected by comorbidities (1). However, the limited evidence comparing different treatment strategies in PsA is recognised as a limitation in these recommendations and further information is detailed below.

  5. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Expert Ask a Question Physician Corner RAVE: The Rheumatoid Arthritis Vital Education Initiative Rheumatology Conference Rheumatology Rounds Case Rounds Radiology Rounds Pathophysiology of the Rheumatic Diseases Our Research Patient-Centered ...

  6. Fetal Programming in Rheumatoid Arthritis

    NARCIS (Netherlands)

    F.D.O. de Steenwinkel (Florentien)

    2013-01-01

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

  7. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... any advice you receive from your rheumatologist. Click A Link Below To Play Rheumatoid Arthritis: Symptoms and ... System Don’t have SilverLight? Get it here. A Small Favor More than 15 years ago the ...

  8. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... it here. A Small Favor More than 15 years ago the Arthritis Center launched this website with ... valuable information to over 1 million visitors each year. Contribute Today More Ways to Give Updated: July ...

  9. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Sheets Benefits and Risks of Opioids in Arthritis Management How to Give a Subcutaneous Injection ... website is intended for educational purposes only. Physicians and other health care professionals are encouraged to consult other sources ...

  10. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Studies The Camille Julia Morgan Arthritis Research and Education Fund About Us Appointment Information Contact Us Our ... the mission to bring current and accurate disease education to health care professionals and patients alike. Content ...

  11. Uveitis in juvenile chronic arthritis.

    Science.gov (United States)

    Kanski, J J

    1990-01-01

    About 20% of patients with juvenile chronic arthritis develop uveitis which is frequently bilateral. Risk factors for uveitis are: female gender, pauciarticular onset of arthritis, presence of circulating antinuclear antibodies, and the antigens HLA-DW5 and HLA-DPw2. The visual prognosis in patients with uveitis is good in 25% and fair in 50%. The remaining 25% develop cataract and/or glaucoma. The management of glaucoma is unsatisfactory, but the results of cataract surgery by lensectomy are good.

  12. Arthritis in America PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2017-03-07

    This 60 second public service announcement is based on the March 2017 CDC Vital Signs report. Many adults in the United States have arthritis. Learn how to reduce the pain of arthritis, as well as manage the condition.  Created: 3/7/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 3/7/2017.

  13. Fatigue in Rheumatoid Arthritis.

    Science.gov (United States)

    Katz, Patricia

    2017-05-01

    The purpose of this study was to review the current information on fatigue in rheumatoid arthritis (RA). Severe fatigue is common among individuals with RA and has a significant impact on quality of life (QOL). RA-related factors (e.g., inflammation, pain) are associated with greater fatigue, but other factors, such as obesity, physical inactivity, sleep disturbance, and depression, explain the majority of variation in fatigue. Medications targeting RA have little effect on fatigue. Instead, the most effective interventions seem to address non-RA-specific factors such as physical inactivity or use cognitive behavioral approaches. No recommendations have been made for tools to measure fatigue in RA, leading to potential difficulty comparing studies. Although fatigue has great impact on patients' QOL, effective interventions that are feasible for broad dissemination remain elusive. Additional multi-faceted research is needed to identify modifiable sources of fatigue. Such research would be enhanced by harmonization of fatigue measurement across studies.

  14. Smoking and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Kathleen Chang

    2014-12-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs, there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper.

  15. Artritis Temprana Early Arthritis

    Directory of Open Access Journals (Sweden)

    2011-02-01

    Full Text Available Hasta la década de los años ochenta se consideraba a la artritis reumatoide (AR como una enfermedad poco frecuente, de gravedad leve a moderada, que tenía una evolución lentamente, progresiva hacia el daño articular y la incapacidad. El aborde terapéutico convencional hasta ese momento, era el tratamiento clásico de la pirámide.Until the early the eighties was considered rheumatoid arthritis to (RA as a rare disease of mild to moderate severity, which had a slowly evolution towards joint damage and disability. The conventional therapeutic option until then, was the classic treatment of the pyramid.

  16. Physiotherapy in rheumatoid arthritis.

    Science.gov (United States)

    Kavuncu, Vural; Evcik, Deniz

    2004-05-17

    Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented.

  17. Juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Krupa H Bhatt

    2014-01-01

    Full Text Available Juvenile Idiopathic Arthritis (JIA is the most chronic musculoskeletal disease of pediatric population. The chronic course of disease has a great impact on oral health. Temporomandibular joint is involved in JIA causing limited mouth opening with progressive open bite, retrognathia, microgenia and bird like appearance. Joints of upper and lower extremities are also involved. Effect on upper limb function leads to difficulty with fine motor movements required for brushing and flossing. This increases incidence of caries and periodontal disease in children. The cause of JIA is still poorly understood and none of the available drugs for JIA can cure the disease. However, prognosis has improved as a result of progress in disease classification and management. The dental practitioner should be familiar with the symptoms and oral manifestations of JIA to help manage as multidisciplinary management is essential.

  18. Biologic therapy of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Damjanov Nemanja

    2009-01-01

    Full Text Available Rheumatoid arthritis (RA and juvenile idiopathic/rheumatoid arthritis (JIA are chronic, inflammatory, systemic, auto-immune diseases characterized by chronic arthritis leading to progressive joint erosions. The individual functional and social impact of rheumatoid arthritis is of great importance. Disability and joint damage occur rapidly and early in the course of the disease. The remarkably improved outcomes have been achieved initiating biologic therapy with close monitoring of disease progression. Biologic agents are drugs, usually proteins, which can influence chronic immune dysregulation resulting in chronic arthritis. According to the mechanism of action these drugs include: 1 anti-TNF drugs (etanercept, infiximab, adalimumab; 2 IL-1 blocking drugs (anakinra; 3 IL-6 blocking drugs (tocilizumab; 4 agents blocking selective co-stimulation modulation (abatacept; 5 CD 20 blocking drugs (rituximab. Biologics targeting TNF-alpha with methotrexate have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. The new concept of rheumatoid arthritis treatment defines early diagnosis, early aggressive therapy with optimal doses of disease modifying antirheumatic drugs (DMARDs and, if no improvement has been achieved during six months, early introduction of biologic drugs. The three-year experience of biologic therapy in Serbia has shown a positive effect on disease outcome.

  19. Fish Eaters Report Less Rheumatoid Arthritis Pain

    Science.gov (United States)

    ... fullstory_166848.html Fish Eaters Report Less Rheumatoid Arthritis Pain Study suggests most fish may play role ... reduce the pain and swelling associated with rheumatoid arthritis, a new study says. Prior studies have shown ...

  20. Understanding Rheumatoid Arthritis (RA): Treatment and Causes

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  1. Having Rheumatoid Arthritis May Increase Heart Risk

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_162038.html Having Rheumatoid Arthritis May Increase Heart Risk Treating inflammation linked to ... TUESDAY, Nov. 15, 2016 (HealthDay News) -- People with rheumatoid arthritis may have an increased risk for a heart ...

  2. Celecoxib for rheumatoid arthritis.

    Science.gov (United States)

    Fidahic, Mahir; Jelicic Kadic, Antonia; Radic, Mislav; Puljak, Livia

    2017-06-09

    Rheumatoid arthritis is a systemic auto-immune disorder that causes widespread and persistent inflammation of the synovial lining of joints and tendon sheaths. Presently, there is no cure for rheumatoid arthritis and treatment focuses on managing symptoms such as pain, stiffness and mobility, with the aim of achieving stable remission and improving mobility. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID) used for treatment of people with rheumatoid arthritis. To assess the benefits and harms of celecoxib in people with rheumatoid arthritis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials registers (ClinicalTrials.gov and the World Health Organization trials portal) to May 18, 2017. We also searched the reference and citation lists of included studies. We included prospective randomized controlled trials (RCTs) that compared oral celecoxib (200 mg and 400 mg daily) versus no intervention, placebo or a traditional NSAID (tNSAID) in people with confirmed rheumatoid arthritis, of any age and either sex. We excluded studies with fewer than 50 participants in each arm or had durations of fewer than four weeks treatment. We used standard methodological procedures expected by The Cochrane Collaboration. We included eight RCTs with durations of 4 to 24 weeks, published between 1998 and 2014 that involved a total of 3988 adults (mean age = 54 years), most of whom were women (73%). Participants had rheumatoid arthritis for an average of 9.2 years. All studies were assessed at high or unclear risk of bias in at least one domain. Overall, evidence was assessed as moderate-to-low quality. Five studies were funded by pharmaceutical companies. Celecoxib versus placeboWe included two studies (N = 873) in which participants received 200 mg daily or 400 mg daily or placebo. Participants who received celecoxib showed significant clinical improvement compared with those receiving placebo (15% absolute

  3. 9 CFR 311.7 - Arthritis.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Arthritis. 311.7 Section 311.7 Animals... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.7 Arthritis. (a) Carcasses affected with arthritis which is localized and not associated with systemic change may be passed for human...

  4. Rheumatoid Arthritis: "You Are Not Alone."

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Rheumatoid Arthritis: "You Are Not Alone." Past Issues / Summer 2014 ... Contents Members of the America 2 Anywhere 4 Arthritis (A2A4A) running group after finishing a marathon. Through ...

  5. Differential Diagnosis of Polyarticular Arthritis.

    Science.gov (United States)

    Pujalte, George G A; Albano-Aluquin, Sheila A

    2015-07-01

    Polyarticular arthritis is commonly encountered in clinical settings and has multiple etiologies. The first step is to distinguish between true articular pain and nonarticular or periarticular conditions by recognizing clinical patterns through the history and physical examination. Once pain within a joint or joints is confirmed, the next step is to classify the pain as noninflammatory or inflammatory in origin. Noninflammatory arthritis, which is mostly related to osteoarthritis, has a variable onset and severity and does not have inflammatory features, such as warm or swollen joints. Osteoarthritis usually presents with less than one hour of morning stiffness and pain that is aggravated by activity and improves with rest. A review of systems is usually negative for rashes, oral ulcers, or other internal organ involvement. In contrast, inflammatory arthritis generally causes warm, swollen joints; prolonged morning stiffness; and positive findings on a review of systems. Once inflammatory arthritis is suspected, possible diagnoses are sorted by the pattern of joint involvement, which includes number and type of joints involved, symmetry, and onset. The suspicion for inflammatory arthritis should be confirmed by the appropriate serologic/tissue and/or imaging studies in the clinical setting or in consultation with a subspecialist.

  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. Pregnancy and rheumatoid arthritis.

    Science.gov (United States)

    Ince-Askan, Hilal; Dolhain, Radboud J E M

    2015-01-01

    Fertility is impaired in female patients with rheumatoid arthritis (RA), which is related to disease activity and the use of certain medication. During pregnancy, disease activity usually improves, but less than previously thought. Especially in women with high disease activity, the pregnancy outcome is also impaired. All of this underscores the importance of strict control of disease activity in RA patients who wish to conceive. Management of RA disease activity during pregnancy might be a challenge as the treatment options are limited. Evidence is accumulating that tumor necrosis factor (TNF) blockers can be safely used during pregnancy, particularly during the first trimester and the beginning of the second trimester. Far less is known about the problems faced by male RA patients who wish to conceive, in terms of not only fertility and pregnancy outcome but also the safety of medication. In this paper, the fertility issues in patients with RA, the pregnancy-associated improvement of RA, the pregnancy outcomes, including the long-term effects on the offspring, and treatment options, including those during lactation and for male patients wishing to conceive, will be reviewed.

  8. RHEUMATOID ARTHRITIS AND PREGNANCY

    Directory of Open Access Journals (Sweden)

    N. M. Kosheleva

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA generally starts at the age when many women have already become mothers; however, it may occur in childhood or adolescence. Furthermore, there has been recently a women’s tendency to plan pregnacy for a more mature age, which necessitates a discussion about gestation in this disease. Investigation of mechanisms pregnancy can influence the development of RA both in the gestation and long-term periods is of important theoretical and practical value. The results of these investigations may be used to develop new treatments for RA and management tactics for patients during pregnancy and lactation. The  aper gives the data available in the literature on fertility in RA, impact of pregnancy on its activity and that of RA on the course and outcomes of gestation, as well as current ideas on lactation and use of oral contraceptives in RA. Particular attention is given to drug therapy in pregnant and breastfeeding women with RA: groups of anti-rheumatic drugs are considered in detail in relation to the safety of or a potential risk from their use. A therapeutic algorithm and recommendations for pregnancy planning and a follow-up of patients with RA during gestation are proposed.

  9. Pregnancy and rheumatoid arthritis.

    Science.gov (United States)

    Tandon, Vishal R; Sharma, Sudhaa; Mahajan, Annil; Khajuria, Vijay; Kumar, Ajay

    2006-08-01

    Pregnancy in most cases, is associated with remission of rheumatoid arthritis (RA), but a quarter of patients continue to have active disease or even worsening of the disease and most patients who improve, relapse in the postpartum period. The pathophysiology of this improvement in disease activity during pregnancy remains unknown, but hormonal, cell-mediated immunological and humoral immunological changes during pregnancy, have been proposed responsible for this. Most of the pregnant women with RA have an uneventful course, with no significant complications. In general, no significant increase in maternal or fetal morbidity seems to be attributable to RA. Patients with RA do not have decreased fertility. A majority of patients with RA may go in remission and anti-rheumatic treatment may not be required as soon as women become pregnant. But other patients who continue with the disease activity require treatment. The preferred disease-modifying agents during pregnancy are sulfasalazine and hydroxychloroquine. Azathioprine and cyclosporine can be used if the benefits outweigh the risks. Paracetamol and low dose prednisone are preferred and considered safe, both for mother and fetus. Methotrexate and lefunomide are contraindicated and must be prophylactically withdrawn before a planned pregnancy. Biologics generally should be stopped when pregnancy is discovered. An overall rational approach is highly warranted to treat RA during pregnancy.

  10. [Pathophysiology of rheumatoid arthritis].

    Science.gov (United States)

    Lequerré, Thierry; Richez, Christophe

    2012-10-01

    These last years were especially marked by the best understanding of the physiopathological mechanisms at the onset of rheumatoid arthritis (RA) and in the processes of joint inflammation and joint destruction. RA is more and more considered as a syndrome with at least two clinical entities with different phenotype and profiles: seronegative RA and seropositive RA. In RA with ACPA, it is the process of immunization, that is the immunological reaction against citrullinated peptides, that leads to the disease. The peptide citrullination is directly favored by environmental factors such as tobacco, infection to Porphyromonas gingivalis and alcohol. The immunization supposes a genetic predisposition including approximately 22 genetic factors including the molecules of the major histocompatibility complex (MHC) and PTPN22. Finally, joint damage result at the same time from an excess of destruction (RANK/RANKL, TNFalpha) and from a defect of bone reparation by the way Wnt/Frizzled. It is thanks to the best understanding of RA physiopathology that leads to development of targeted treatments and specially processing for this disease.

  11. Prostaglandins and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Fattahi

    2012-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic, autoimmune, and complex inflammatory disease leading to bone and cartilage destruction, whose cause remains obscure. Accumulation of genetic susceptibility, environmental factors, and dysregulated immune responses are necessary for mounting this self-reacting disease. Inflamed joints are infiltrated by a heterogeneous population of cellular and soluble mediators of the immune system, such as T cells, B cells, macrophages, cytokines, and prostaglandins (PGs. Prostaglandins are lipid inflammatory mediators derived from the arachidonic acid by multienzymatic reactions. They both sustain homeostatic mechanisms and mediate pathogenic processes, including the inflammatory reaction. They play both beneficial and harmful roles during inflammation, according to their site of action and the etiology of the inflammatory response. With respect to the role of PGs in inflammation, they can be effective mediators in the pathophysiology of RA. Thus the use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in RA. In this paper, we try to elucidate the role of PGs in the immunopathology of RA.

  12. 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.

  13. Overview of the radiology of juvenile idiopathic arthritis (JIA)

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, P.A.; Job-Deslandre, C.H.; Lalande, G.; Adamsbaum, C

    2000-02-01

    Plain films remain the basic tool for diagnosis and follow-up evaluation of juvenile idiopathic arthritis (JIA). In this paper, we review the new classification of JIA: systemic arthritis, oligoarthritis (persistent), oligoarthritis (extended), polyarticular arthritis (rheumatoid factor negative), polyarticular arthritis (rheumatoid factor positive), enthesitis related arthritis, psoriatic arthritis and unclassified arthritis. We will also review regional abnormalities of three stages: an early stage, an intermediate stage, a late stage, as well as the differential diagnosis.

  14. BIOBEHAVIORAL THERAPY OF RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    N. A. Shabanova

    2013-01-01

    Full Text Available The relevance of the study is connected with need to expand the arsenal of treatment methods patients with rheumatoid arthritis. The study examined the efficacy of biobehavioral therapy in a comprehensive program of treatment patients with rheumatoid arthritis (medical therapy in combination with biobehavioral therapy. It has been shown when compared with the control group (isolated drug therapy maintaining  clinical  response  in  short-term  follow-up  study  in  the  intervention  group.  Statistically    significant relationship the volitional control of the alpha rhythm of EEG (increased power of the alpha rhythm with a reduction in pain intensity in the in neurofeedback program and positive dynamics of the main characteristics of the alpha rhythm have been drmonstrated. Inclusion in the treatment program of arthritis biobehavioral approach has reduced the dose of pain medication, so reducing aggression of pharmacotherapy.

  15. Identifying flares in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H

    2016-01-01

    Set. METHODS: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares...... to flare, with escalation planned in 61%. CONCLUSIONS: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with...

  16. Dietetic recommendations in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    María Rosa Alhambra-Expósito

    2013-12-01

    Full Text Available Rheumatoid arthritis (RA is a chronic autoimmune disease that has a significant effect on patients’ physical, emotional, and social functioning. For decades, patients have used different diets to try to improve the symptoms of RA. The possible benefits of dietary therapy for rheumatoid arthritis are reviewed in this article. Nutritional objectives for RA, are to halt the loss of bone mass, promote healing of bone fractures and improving bone-associated inflammatory disorders and joints. In general, diets low in saturated fat, rich in polyunsaturated fats: omega 3 and omega 6, rich in complex carbohydrates and fiber are recommended.

  17. Cutaneous manifestations of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Bhanu Prakash

    2015-02-01

    Full Text Available Rheumatoid arthritis (RA is a multisystem autoimmune disease, affecting the joints predominantly, and extra-articular sites like skin, lungs, heart etc. The American College of Rheumatology (ACR in collaboration with the European League Against Rheumatism (EULAR in 2010, revised the 1987 ACR classification criteria for RA. The criteria covered four areas (joint involvement, serodiagnosis, acute phase reactants, duration of arthritis and established a point value on a scale of 0 to 10. Patients with a value of 6 or higher are classified as having RA.

  18. Rituximab for Rheumatoid Arthritis.

    Science.gov (United States)

    Cohen, Marc D; Keystone, Edward

    2015-12-01

    Rituximab is a chimeric monoclonal antibody directed at the CD20 molecule on the surfaces of some but not all B cells. It depletes almost all peripheral B cells, but other niches of B cells are variably depleted, including synovium. Its mechanism of action in rheumatoid arthritis (RA) is only partially understood. Rituximab was efficacious in clinical trials of patients with RA, including those who are methotrexate naïve, those with an incomplete response to methotrexate, and those with an incomplete response to tumor necrosis factor inhibitors. The need for a concomitant traditional disease-modifying drug, the optimal dose of rituximab, and the optimal interval for retreatment remain somewhat uncertain. Rituximab seems to be most efficacious in seropositive patients and those with an incomplete response to only one tumor necrosis factor inhibitor. Rituximab has a reasonable safety profile, with a small risk of serious infectious events, which is stable over time and repeat courses. Opportunistic infections are rare. Reactivation of hepatitis B remains a concern. The possible association of rituximab and progressive multifocal leukoencephalopathy may still require vigilance. Malignancies and cardiovascular events do not appear to be increased. Infusion reactions are more likely with the initial infusion, and are usually mild. Rituximab may cause hypogammaglobulinemia, but any risk of subsequent risk of increased infectious events is not yet well established. Before initiating rituximab, patient screening for hypersensitivity to murine proteins, infections, congestive heart failure, pregnancy, and hypogammaglobulinemia is imperative. Vaccinations should be administered prior to treatment whenever possible. Rituximab has been a significant addition to the rheumatologists' armamentarium for the treatment of RA.

  19. Rheumatoid arthritis and pigmented villonodular synovitis: comparative analysis of cell polyploidy, cell cycle phases and expression of macrophage and fibroblast markers in proliferating synovial cells.

    Science.gov (United States)

    Berger, I; Weckauf, H; Helmchen, B; Ehemann, V; Penzel, R; Fink, B; Bernd, L; Autschbach, F

    2005-05-01

    Rheumatoid arthritis (RA) and pigmented villonodular synovitis (PVNS) are aggressive diseases with progressive joint destruction. The present study aims to define cell cycle phases, polyploidy and the immunophenotype of proliferating synovial cells in both diseases. Synovial tissues from patients with proliferative-active RA, localized and diffuse PVNS were analysed by DNA flow cytometry, immunohistochemistry and double immunofluorescence with confocal laser scan microscopy. Expression of macrophage markers (CD68/CD163), fibroblast markers (h4Ph/CD55) and Ki67 antigen was examined. Synovial cells positive for either macrophage or fibroblast markers as well as double-labelled cells were found in both RA and PVNS. In RA, CD68/CD163+ synoviocytes were preferentially located in the vicinity of the synovial lining layer, while they were more randomly distributed in PVNS. Of cases with diffuse PVNS, 20% showed an aneuploid cell pattern. All samples of localized PVNS and RA were diploid. Proliferative activity was significantly higher in aneuploid PVNS. In spite of their histologically homogeneous appearance, proliferating synovial cells display a heterogeneous immunophenotype in both RA and PVNS, indicating functional properties of both macrophages and fibroblasts. Aneuploidy seems to be a special feature of diffuse PVNS.

  20. SEPTIC ARTHRITIS OF THE HIP IN ADULTS: A RARE PRESENTATION

    OpenAIRE

    Kuppa; Yerukala; Dema; Sujith; Venkateswar Reddy

    2015-01-01

    Septic Arthritis also known as infectious arthritis, can be bacterial or fungal arthritis. The condition is an inflammation of a joint that is caused by an infection. Typically, Septic Arthritis affects one large joint in the body such as knee or hip. Generally, Septic Arthritis is present with complete absorption of the head of the ...

  1. Vagal influences in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Rasmussen, S E; Pfeiffer-Jensen, M; Drewes, A M

    2017-01-01

    Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease with a prevalence of 0.5-1% in Western populations. Conventionally, it is treated with therapeutic interventions that include corticosteroids, disease-modifying anti-rheumatic drugs, and biological agents. RA exerts...

  2. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J

    2010-01-01

    BACKGROUND: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). OBJECTIVE: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS...

  3. Diagnostic Delay in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Mølbaek, Karen; Hørslev-Petersen, Kim; Primdahl, Jette

    2016-01-01

    BACKGROUND: To prevent joint damage among patients with rheumatoid arthritis (RA), there is a need to minimize delays from the onset of symptoms until the initiation of appropriate therapy. The present study explored the factors that have an impact on the time it takes for Danish patients with RA...

  4. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Breedveld, Ferdinand C; Burmester, Gerd R

    2016-01-01

    BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards...

  5. Glucocorticoid Sensitivity in Rheumatoid Arthritis

    NARCIS (Netherlands)

    R.A.M. Quax

    2013-01-01

    textabstractAccumulating observations of women with rheumatoid arthritis (RA) who ‘spontaneously’ experienced less active disease during pregnancy led to the growing belief by Philip Hench that a hormonal substance had to be involved in the improving clinical conditions of pregnant patients with RA.

  6. Genetics in juvenile idiopathic arthritis

    NARCIS (Netherlands)

    Albers, Heleen Marion

    2015-01-01

    Juvenile idiopathic arthritis (JIA) is a non-common disease in children that can persist into adulthood. JIA is considered to be an auto-immune disease. Genetic factors play a role in the pathogenesis. In a new cohort of JIA patients from North-West European descent genetic candidate gene associatio

  7. Citrullinated Chemokines in Rheumatoid Arthritis

    Science.gov (United States)

    2014-10-01

    Clavel C, Arnaud J, Nogueira L, et al. Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated... Clavel C, Chapuy-Regaud S, Al Badine R, Mechin MC, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are

  8. Abatacept treatment for rheumatoid arthritis

    National Research Council Canada - National Science Library

    Schiff, Michael

    2011-01-01

    ... of aggressive, erosive disease. Here, one such biologic therapy, the T-cell co-stimulation modulator abatacept, is discussed, exploring clinical evidence published to date on its use in patients with very early arthritis/early RA who are MTX...

  9. Glucocorticoids in early rheumatoid arthritis

    NARCIS (Netherlands)

    Everdingen, Amalia A. van

    2002-01-01

    For 50 years, glucocorticoids (GC) are used for symptomatic treatment of rheumatoid arthritis (RA). In the last decade, results from clinical studies of treatment with GC as additional therapy to long-acting antirheumatic drugs in patients with early RA suggested also disease-modifying properties of

  10. COMORBIDITY IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    T. A. Panafidina

    2014-01-01

    Full Text Available The peak onset of rheumatoid arthritis (RA is at 30-55 years of age. At this age, the patients have also other concomi- tant diseases (comorbidities that affect the course and prognosis of RA, the choice of its treatment policy, quality of life of the patients. Objective: to identify the most important and common comorbidities in patients with RA. Subjects and methods. Two hundred patients (median age 55 [46; 61] years were enrolled; there was a preponderance of women (82.5% with median disease duration 5 [1; 10] years, seropositive for IgM rheumatoid factor (83.0% and anti-cyclic citrullinated peptide antibodies (81.6% with moderate and high disease activity (median DAS28 value 3.9 [3.1; 4.9]. Varying degrees of destructive changes in hand and foot joints were radiologically detected in 71.2% of the patients; 64.5% of the patients had Functional Class II. Methotrexate was given to 69.5% of the patients; therapy with biological agents was used in 21.0% of the cases. 15.5% of the patients did not receive DMARD or biologics. 43.0% of the patients with RA received glucocorticoids. Results. Comorbidities were present in 72.0% of the patients with RA. The most common diseases were hypertension (60.0%, dyslipidemia (45.0%, fractures at various sites (29.5%, and coronary heart disease (21.0%. Myocardial infarction and stroke were observed in 1.5 and 1.0% of cases, respectively. There was diabetes mellitus (DM in 7.5% of the cases and osteoporosis in 15.5% of the patients. 81.7% of the patients with RA and hypertension and 80.0% of those with RA and DM received antihypertensive and sugar-lowering therapy, respectively. At the same time the RA patients with dyslipidemia and osteoporosis received specific drugs far less frequently (30.0 and 29.0%, respectively. Conclusion. Comorbidities are frequently encountered in RA. By taking into account the fact that cardiovascular dis- eases are a main cause of death in RA; it is necessary to adequately and timely

  11. Anti-proliferative effects of Salacia reticulata leaves hot-water extract on interleukin-1β-activated cells derived from the synovium of rheumatoid arthritis model mice

    Directory of Open Access Journals (Sweden)

    Sekiguchi Yuusuke

    2012-04-01

    Full Text Available Abstract Background Salacia reticulata (SR is a plant native to Sri Lanka. In ayurvedic medicine, SR bark preparations, taken orally, are considered effective in the treatment of rheumatism and diabetes. We investigated the ability of SR leaves (SRL to inhibit in vitro the interleukin-1β (IL-1β-activated proliferation of synoviocyte-like cells derived from rheumatoid arthritis model mice. Findings Inflammatory synovial tissues were harvested from type II collagen antibody-induced arthritic mice. From these tissues, a synoviocyte-like cell line was established and named MTS-C H7. To determine whether SRL can suppress cell proliferation and gene expression in MTS-C H7 cells, fractionation of the SRL hot-water extract was performed by high-performance liquid chromatography (HPLC, liquid-liquid extraction, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE, and protease digestion. The 50% inhibitory concentration of the SRL hot-water extract against MTS-C H7 cells proliferation was ~850 μg/mL. Treatment with a low dose (25 μg dry matter per millilitre of the extract inhibited IL-1β-induced cell proliferation and suppressed the expression of the matrix metalloproteinase (MMP genes in MTS-C H7 cells. Various polyphenolic fractions obtained from HPLC and the fractions from liquid-liquid extraction did not affect cell proliferation. Only the residual water sample from liquid-liquid extraction significantly affected cell proliferation and the expression of MMP genes. The results of SDS-PAGE and protease digestion experiment showed that low molecular weight proteins present in SRL inhibited the IL-1β-activated cell proliferation. Conclusions We surmised that the residual water fraction of the SRL extract was involved in the inhibition of IL-1β-activated cell proliferation and regulation of mRNA expression in MTS-C H7 cells. In addition, we believe that the active ingredients in the extract are low molecular weight proteins.

  12. 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.

  13. Polyarticular septic arthritis in an immunocompetent patient.

    Science.gov (United States)

    Clements, J; Dinneen, A; Heilpern, G

    2013-03-01

    Septic arthritis is an uncommon condition with an incidence of 2-3/100,000. It is clinically notable, however, as it is a rapidly destructive joint disease with significant associated morbidity and mortality. Polyarticular septic arthritis has an estimated incidence of 15% of all cases of infectious arthritis. We report a case of polyarticular septic arthritis with involvement of bilateral shoulders and wrist to highlight the importance of early diagnosis and treatment as well as the high mortality rates associated with this condition. Bilateral septic shoulder arthritis poses a challenge to treat, and its significance should not be underestimated as even with early surgical intervention and aggressive antibiotic and fluid resuscitation death is a sad but perhaps not uncommon outcome. It is therefore imperative that the diagnosis of polyarticular septic arthritis is kept prominent in the physician's mind when confronted with a patient with symptomatic polyarthralgia.

  14. Improved early identification of arthritis : evaluating the efficacy of Early Arthritis Recognition Clinics

    NARCIS (Netherlands)

    van Nies, Jessica A. B.; Brouwer, Elisabeth; van Gaalen, Floris A.; Allaart, Cornelia F.; Huizinga, Tom W. J.; Posthumus, Marcel D.; van der Helm-van Mil, Annette H. M.

    Objective Only 31% of Dutch rheumatoid arthritis (RA)-patients visit a rheumatologist within 12weeks after symptom onset; this is mainly due to delay at the level of the general practitioner (GP). In order to reduce delay of GPs in identifying early arthritis, we initiated an Early Arthritis

  15. Septic arthritis due to Roseomonas mucosa in a rheumatoid arthritis patient receiving infliximab therapy.

    Science.gov (United States)

    Sipsas, Nikolaos V; Papaparaskevas, Joseph; Stefanou, Ioanna; Kalatzis, Konstantinos; Vlachoyiannopoulos, Panayiotis; Avlamis, Athina

    2006-08-01

    We report a case of septic arthritis due to Roseomonas mucosa in a rheumatoid arthritis patient receiving infliximab therapy. This is the first report of septic arthritis due to R. mucosa, and infliximab therapy might be a predisposing factor because this infection was never reported in the pre-anti-tumor necrosis factor alpha therapy period.

  16. Acromioclavicular septic arthritis and sternoclavicular septic arthritis with contiguous pyomyositis.

    Science.gov (United States)

    Corey, Sally A; Agger, William A; Saterbak, Andrew T

    2015-03-01

    Acromioclavicular (AC) and sternoclavicular (SC) septic arthritis with contiguous pyomyositis are rare, especially in immunocompetent individuals. We report a case of septic AC joint with pyomyositis of the deltoid and supraspinatus muscles and a separate case with septic SC joint with pyomysitis of the sternocleidomastoid muscle. Both patients had similar presentations of infections with Staphylococcus aureus and were successfully treated with surgical incision and drainage followed by prolonged antibiotic therapy.

  17. 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...

  18. Polyarticular septic arthritis following septic circumcision.

    Science.gov (United States)

    Millar, Tim M; McGrath, Patrick; McConnachie, Charles C

    2007-01-01

    Ritual circumcision during an initiation ceremony for young adults is common practice in parts of South Africa. We report on a case of polyarticular septic arthritis in a seventeen-year-old man following septicaemia after circumcision, resulting in severe fixed flexion deformities of both knees. This case illustrates an unusual cause of polyarticular septic arthritis and the treatment difficulties associated with delayed presentation. It is also a reminder of the consequences of untreated acute septic arthritis.

  19. Pathogenesis and Prediction of Future Rheumatoid Arthritis

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-13-1-0408 TITLE: Pathogenesis and Prediction of Future Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Kevin D. Deane, MD/PhD...order to understand two major factors: 1) how biomarker changes in preclinical RA can be used to accurately predict the future development of RA in...will be performed. 15. SUBJECT TERMS Prediction of future rheumatoid arthritis; pathogenesis of rheumatoid arthritis 16. SECURITY CLASSIFICATION OF

  20. Septic arthritis in immunocompetent and immunosuppressed hosts.

    Science.gov (United States)

    Wang, Dingyuan Alvin; Tambyah, Paul Anantharajah

    2015-04-01

    Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases.

  1. Can magnetic resonance imaging differentiate undifferentiated arthritis?

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Duer, Anne; Hørslev-Petersen, K

    2005-01-01

    A high sensitivity for the detection of inflammatory and destructive changes in inflammatory joint diseases makes magnetic resonance imaging potentially useful for assigning specific diagnoses, such as rheumatoid arthritis and psoriatic arthritis in arthritides, that remain undifferentiated after...... conventional clinical, biochemical and radiographic examinations. With recent data as the starting point, the present paper describes the current knowledge on magnetic resonance imaging in the differential diagnosis of undifferentiated arthritis....

  2. 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.

  3. Retinal occlusive vasculer disorder and rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Huseyin Ortak

    2013-03-01

    Full Text Available Rheumatoid arthritis is a systemic inflammatory disease that affected older women with many ocular manifestations. Also, these systemic diseases can cause retinal vein occlusion and arterial occlusion that lead to serious and permanent visual loss. Rheumatoid arthritis's the most common manifestation is that retinal vasculitis and retinal vascular complications are associated with this complication. In this review, retinal vascular occlusive diseases are presented to associated with rheumatoid arthritis in literature. Rheumatoid arthritis and its complications have been outlined and was made to create a new perspective. [J Contemp Med 2013; 3(1.000: 71-73

  4. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  5. Fungal osteomyelitis and septic arthritis.

    Science.gov (United States)

    Bariteau, Jason T; Waryasz, Gregory R; McDonnell, Matthew; Fischer, Staci A; Hayda, Roman A; Born, Christopher T

    2014-06-01

    Management of fungal osteomyelitis and fungal septic arthritis is challenging, especially in the setting of immunodeficiency and conditions that require immunosuppression. Because fungal osteomyelitis and fungal septic arthritis are rare conditions, study of their pathophysiology and treatment has been limited. In the literature, evidence-based treatment is lacking and, historically, outcomes have been poor. The most common offending organisms are Candida and Aspergillus, which are widely distributed in humans and soil. However, some fungal pathogens, such as Histoplasma, Blastomyces, Coccidioides, Cryptococcus, and Sporothrix, have more focal areas of endemicity. Fungal bone and joint infections result from direct inoculation, contiguous infection spread, or hematogenous seeding of organisms. These infections may be difficult to diagnose and eradicate, especially in the setting of total joint arthroplasty. Although there is no clear consensus on treatment, guidelines are available for management of many of these pathogens.

  6. Clinimetric criteria of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Domenico Galasso

    2012-10-01

    Full Text Available Rheumatoid arthritis is a systemic autoimmune disease, mainly poli-artycular, among wide-spread chronic inflammatory diseases, that cause pain, functional limitation, damage and joints deformations, and disability. It is characterized by turns of active inflammation and remission phases. Inflammation degree and persistence are associated to a bad functional prognosis and progressive joint disability. These patients management require a continuous valuation of inflammatory activity index of disease both therapeutic management and to prevent disablement process. We focus on many valuation index of joint disability and functional damage. Very important are both the scales of auto-values concerning the pain and the joint swelling and clinical data get by physician to valuate activity index of disease as defined by DAS28. Significant data come by health-related quality of life, disability and by AIMS2 (Arthritis Impact Measurement Scale.

  7. Nutritional considerations in rheumatoid arthritis.

    Science.gov (United States)

    Touger-Decker, R

    1988-03-01

    Rheumatoid arthritis is a chronic, systemic, inflammatory disorder of unknown etiology. The severity of the disease process adversely affects nutritional status. Articular changes, such as small joint deformities and temporomandibular joint syndrome, alter the ability to self-feed. The inflammatory process may increase metabolic rate. Ingestion, digestion, absorption, and excretion may be compromised by secondary manifestations of the disease. Comprehensive nutrition assessment incorporates evaluation of disease and treatment-specific factors, along with the usual assessment parameters. Abnormal values for certain assessment parameters do not necessarily reflect nutritional status. Treatment methods, including medications, may have an impact on nutritional status, assessment tools, and self-feeding. Nutrition management goals focus on identification and implementation of feeding strategies. Evaluation of the ability to feed oneself includes consideration of functional status, secondary manifestations, and medical treatment. Multiple feeding modalities may be required. Oral supplements, tube feedings, and parenteral nutrition may be employed to meet the nutrition needs of the individual with rheumatoid arthritis.

  8. Emerging immunotherapies for rheumatoid arthritis

    Science.gov (United States)

    Reynolds, Gary; Cooles, Faye AH; Isaacs, John D; Hilkens, Catharien MU

    2014-01-01

    Novel treatments in development for rheumatoid arthritis target 3 broad areas: cytokines, cells, and signaling pathways. Therapies from each domain share common advantages (for example previously demonstrated efficacy, potential long-term immunomodulation, and oral administration respectively) that have stimulated research in each area but also common obstacles to their development. In this review recent progress in each area will be discussed alongside the factors that have impeded their path to clinical use. PMID:24535556

  9. Citrullinated Chemokines in Rheumatoid Arthritis

    Science.gov (United States)

    2016-12-01

    modified forms of these proteins may serve as potential autoantigens in RA. References: 1. Yoshida Y, Korchynskyi O, Tak PP, Isozaki T, Ruth JH, Campbell ...recruiting chemokine. Arthritis Rheumatol. 66:2716-27, 2014. 2. Edhayan G, Ha CM, Isozaki T, Amin MA, Ohara RA, Morgan R, Campbell PL, Haines GK III, Arbab S...of RA. 6. Publications, Abstracts and Presentations Peer-reviewed manuscripts: 1. Yoshida Y, Korchynskyi O, Tak PP, Isozaki T, Ruth JH, Campbell PL

  10. Metabolite Space of Rheumatoid Arthritis

    OpenAIRE

    van Wietmarschen, Herman; van der Greef, Jan

    2012-01-01

    Metabolites play numerous roles in the healthy and diseased body, ranging from regulating physiological processes to providing building blocks for the body. Therefore, understanding the role of metabolites is important in elucidating the etiology and pathology of diseases and finding targets for new treatment options. Rheumatoid arthritis is a complex chronic disease for which new disease management strategies are needed. The aim of this review is to bring together and integrate information a...

  11. Rheumatoid arthritis as psychic problem

    Directory of Open Access Journals (Sweden)

    Jiří Kaas

    2014-12-01

    Full Text Available The article deals with the issue of psychic problems of rheumatoid arthritis patients. Rheumatoid arthritis is a chronic, inflammatory motor system disease with comprehensive impact on the patient's life. The disease is often considered an exclusively physical disease. But such approach is insufficient because the disease is accompanied by motor limitations of different intensities, by pain and by fatigue that cause considerable exhaustion to the patient. The patients often must give up their hobbies and in some cases even their jobs. In most serious cases, even common daily activities including self-servicing actions become an obstacle to the patient. It is therefore logical that the psyche of a patient with such disease is considerably strained. One of the partial goals of the study consisted in mapping the subjectively perceived quality of life of rheumatoid arthritis patients in facet 8, "negative feelings", and in ascertaining whether there is statistically significant relation to facets 1, "pain and discomfort", and 2, "energy and fatigue". Another goal consisted in comparing the subjectively perceived quality of life between men and women with rheumatoid arthritis, as well as between population of rheumatoid arthritis patients and control healthy population. The study was implemented within the research project of the Grant Agency of the University of South Bohemia in České Budějovice number 120/2012/S, "Reflection of quality of life in nursing", under use of two standardized questionnaires, WHOQOL-100 and HAQ. This article presents exclusively the data acquired based on the WHOQOL-100 questionnaire. The research set consisted of patients suffering from rheumatoid arthritis from all over the Czech Republic. The size of the set was determined by a statistician at 200 individuals suffering from the disease, in a ratio of 150 women and 50 men. The selection set was derived from the basic set of rheumatoid arthritis patients and can

  12. Rheumatoid arthritis as psychic problem

    Directory of Open Access Journals (Sweden)

    Jiří Kaas

    2014-01-01

    Full Text Available The article deals with the issue of psychic problems of rheumatoid arthritis patients. Rheumatoid arthritis is a chronic, inflammatory motor system disease with comprehensive impact on the patient's life. The disease is often considered an exclusively physical disease. But such approach is insufficient because the disease is accompanied by motor limitations of different intensities, by pain and by fatigue that cause considerable exhaustion to the patient. The patients often must give up their hobbies and in some cases even their jobs. In most serious cases, even common daily activities including self–servicing actions become an obstacle to the patient. It is therefore logical that the psyche of a patient with such disease is considerably strained. One of the partial goals of the study consisted in mapping the subjectively perceived quality of life of rheumatoid arthritis patients in facet 8, "negative feelings", and in ascertaining whether there is statistically significant relation to facets 1, "pain and discomfort", and 2, "energy and fatigue". Another goal consisted in comparing the subjectively perceived quality of life between men and women with rheumatoid arthritis, as well as between population of rheumatoid arthritis patients and control healthy population. The study was implemented within the research project of the Grant Agency of the University of South Bohemia in České Budějovice number 120/2012/S, „Reflection of quality of life in nursing", under use of two standardized questionnaires, WHOQOL–100 and HAQ. This article presents exclusively the data acquired based on the WHOQOL–100 questionnaire. The research set consisted of patients suffering from rheumatoid arthritis from all over the Czech Republic. The size of the set was determined by a statistician at 200 individuals suffering from the disease, in a ratio of 150 women and 50 men. The selection set was derived from the basic set of rheumatoid arthritis patients and

  13. Atherosclerosis in Juvenile Idiopathic Arthritis

    Directory of Open Access Journals (Sweden)

    Ewa Jednacz

    2012-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process occur in the adult population, however atherosclerotic process begins in childhood. The classic risk factors for atherosclerosis include obesity, dyslipidaemia, age, gender or family history. In recent years, attention has been drawn to the similarity between atherosclerotic inflammatory processes and inflammatory changes in the course of systemic connective tissue disease, in particular systemic lupus etythematosus (SLE or rheumatoid arthritis (RA. There is also observed the similarity of the pathogenetic background of development of atherosclerosis and juvenile idiopathic arthritis (JIA. Elevated levels of pro-inflammatory cytokines are observed in the course of juvenile idiopathic arthritis. Also homocysteine concentrations, which may play a significant role in the development of atherosclerotic lesions, are observed higher in patients with JIA. Some studies revealed higher carotid intima-media thickness (IMT index values in children with JIA. In view of the fact that atherosclerotic process begins as early as in childhood, the introduction of appropriate preventive measures in children is a matter of utmost importance.

  14. Parvovirus infection in early arthritis.

    Science.gov (United States)

    Mauermann, Maria; Hochauf-Stange, Kristina; Kleymann, Alexander; Conrad, Karsten; Aringer, Martin

    2016-01-01

    To analyse the subgroup of early arthritis patients with new onset parvovirus infections for details that may help narrow the population tested. From their routine patient charts, patient histories and clinical and serological data were obtained for all 130 patients of the Rheumatology division with parvovirus serology performed. 11 patients had acute parvovirus infections, defined by specific IgM antibodies. 95 patients had a previous infection, 16 were never infected, together forming the n=111 control group, and 8 patients had to be excluded. Most patients with acute parvovirus infection had an acute onset, highly symmetrical polyarthritis of small joints, which was preceded by prodromal symptoms. Positive ANA were frequently found, whereas C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were only mildly elevated. No frank synovitis was found longer than two weeks after disease onset. Most patients were free of symptoms within three months, and no patient in the parvovirus group developed rheumatoid arthritis or a connective tissue disease. Parvovirus serology may be helpful in patients with acute polyarthritis of very recent onset, and if they give a history of prodromal symptoms, in particular. In most instances, parvovirus arthritis is an acute disease, which is rapidly self-limiting.

  15. Report - Recurrent hip arthritis diagnosed as juvenile idiopathic arthritis: A case report.

    Science.gov (United States)

    Chang, Tung-Ming; Yang, Kuender D; Yong, Su-Boon

    2016-05-01

    Juvenile idiopathic arthritis is the most common rheumatic disease in childhood. It is a chronic inflammatory disease associated with arthritis of unknown etiology that begins before the age of 16 and persists for longer than 6 weeks. In this report, the case of a child who suffered recurrent alternative hip arthritis with bilateral hip arthritis is examined, in which he was finally diagnosed as suffering from Juvenile idiopathic arthritis. A 14-year-old boy of Taiwanese origin presented with a normal birth and developmental history. At the age of 10, right-side hip joint pain was experienced, which later migrated to the left side. On further inspection, synovium hypertrophy, cartilage erosion and hip turbid fluid accumulation were found and aseptic arthritis was presumed to be the primary cause. However, after re-examining both his clinical history and presentation, Juvenile idiopathic arthritis was the final diagnosis. Any child presenting with repeat joint swelling are at risk of Juvenile idiopathic arthritis. This is still to be the case if symptoms recede or heal and no initial diagnosis is made. Therefore, a better understanding of the risk of recurrent arthritis is needed. It cannot be emphasized strongly enough that Juvenile idiopathic arthritis should be suspected at all times when a child suffers from recurrent aseptic arthritis of the hip joint.

  16. 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.

  17. Socioeconomic status and risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Klarlund, Mette

    2006-01-01

    To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association.......To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association....

  18. Patient education for adults with rheumatoid arthritis

    NARCIS (Netherlands)

    Riemsma, R.P.; Kirwan, J.R.; Taal, E.; Rasker, H.J.J.

    2009-01-01

    Patient education shows short-term benefits for adults with rheumatoid arthritis. The purpose was to examine the effectiveness of patient education interventions on health status (pain, functional disability, psychological well-being and disease activity) in patients with rheumatoid arthritis (RA).

  19. Autoimmune correlation of rheumatoid arthritis and periodontitis

    OpenAIRE

    Lalitha Tanjore Arunachalam

    2014-01-01

    Rheumatoid arthritis and periodontitis, both, chronic inflammatory diseases share certain common diagnostic, pathological, immunogenetic and therapeutic features. A recently discovered enzymatic mimicry between human and bacterial species is novel and it opens up a new terrain for therapeutic blockade in the management of rheumatoid arthritis.

  20. Treatment of early rheumatoid and undifferentiated arthritis

    NARCIS (Netherlands)

    Heimans, Lotte

    2014-01-01

    This thesis focuses on different aspects of treatment of patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA), based on the results of three intervention studies; the IMPROVED-study, the BeSt study and the PROMPT study. This thesis discusses the results of different treatment

  1. Arthritis and X-linked agammaglobulinemia.

    Science.gov (United States)

    Machado, Pedro; Santos, Alexandra; Faria, Emília; Silva, Jorge; Malcata, Armando; Chieira, Celso

    2008-01-01

    Primary immunodeficiencies are defined as genetically determined functional and/or quantitative abnormalities in one or more of the components of the immune system. Immunodeficiency and arthritis can be related, although the mechanisms are not always clear. Different causes for immunodeficiency can secondarily be found in patients with arthritis; on the other hand, arthritis can be a manifestation of primary immunodeficiency. Arthritis occurs chiefly in humoral primary immunodeficiencies, namely in X-linked agammaglobulinemia and common variable immunodeficiency, and may be one of the warning signs for primary immunodeficiency. We report a case of arthritis as the presenting feature of X-linked agammaglobulinemia. In X-linked agammaglobulinemia, arthritis may be a consequence of infection, most notably by Mycoplasma, or of immune dysfunction itself. In children, and occasionally in young adults, a combination of arthritis and hypogammaglobulinemia should suggest primary immunodeficiency, although other causes of hypogammaglobulinemia must be excluded. Physicians evaluating patients with arthritis should be aware of this fact so that an early diagnosis can be pursued as it is of extreme importance in the optimal management and prognosis of these patients.

  2. Osteoarthritis and rheumatoid arthritis of the carpus

    NARCIS (Netherlands)

    Raven, E.E.J.

    2017-01-01

    Arthritis can be idiopathic or caused by inflammatory disease (for instance rheumatoid arthritis), posttraumatic, congenital, or as a resultant of avascular necrosis of one of the carpal bones. The common factor in all these causes is that the normal biomechanics are disturbed, either by disturbance

  3. Treatment of early rheumatoid and undifferentiated arthritis

    NARCIS (Netherlands)

    Heimans, Lotte

    2014-01-01

    This thesis focuses on different aspects of treatment of patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA), based on the results of three intervention studies; the IMPROVED-study, the BeSt study and the PROMPT study. This thesis discusses the results of different treatment

  4. Symptomatic manubriosternal joint involvement in rheumatoid arthritis.

    OpenAIRE

    1989-01-01

    The manubriosternal joint is commonly involved in rheumatoid arthritis but rarely gives rise to symptoms. A patient is reported with seropositive, erosive rheumatoid arthritis, who developed symptoms resembling pleuritic pain, arising from synovitis of the manubriosternal joint. Treatment with intra-articular steroid injection resolved these symptoms rapidly.

  5. Symptomatic manubriosternal joint involvement in rheumatoid arthritis.

    Science.gov (United States)

    Doube, A; Clarke, A K

    1989-06-01

    The manubriosternal joint is commonly involved in rheumatoid arthritis but rarely gives rise to symptoms. A patient is reported with seropositive, erosive rheumatoid arthritis, who developed symptoms resembling pleuritic pain, arising from synovitis of the manubriosternal joint. Treatment with intra-articular steroid injection resolved these symptoms rapidly.

  6. Biomarkers for rheumatoid and psoriatic arthritis.

    Science.gov (United States)

    Verheul, M K; Fearon, U; Trouw, L A; Veale, D J

    2015-11-01

    Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy.

  7. 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.

  8. Photoacoustic tomography to identify inflammatory arthritis

    Science.gov (United States)

    Rajian, Justin Rajesh; Girish, Gandikota; Wang, Xueding

    2012-09-01

    Identifying neovascularity (angiogenesis) as an early feature of inflammatory arthritis can help in early accurate diagnosis and treatment monitoring of this disease. Photoacoustic tomography (PAT) is a hybrid imaging modality which relies on intrinsic differences in the optical absorption among the tissues being imaged. Since blood has highly absorbing chromophores including both oxygenated and deoxygenated hemoglobin, PAT holds potential in identifying early angiogenesis associated with inflammatory joint diseases. PAT is used to identify changes in the development of inflammatory arthritis in a rat model. Imaging at two different wavelengths, 1064 nm and 532 nm, on rats revealed that there is a significant signal enhancement in the ankle joints of the arthritis affected rats when compared to the normal control group. Histology images obtained from both the normal and the arthritis affected rats correlated well with the PAT findings. Results support the fact that the emerging PAT could become a new tool for clinical management of inflammatory arthritis.

  9. Brucellar sternoclavicular arthritis, the forgotten complication.

    Science.gov (United States)

    Mousa, A M; Muhtaseb, S A; Al-Mudallal, D S; Marafie, A A; Habib, F M

    1988-06-01

    Of 511 cases of brucellosis studied between December 1983 and February 1986, four (0.8%) had sternoclavicular (STCL) arthritis. Two were male and two female, and only one was younger than 50 years old. All four cases had significantly high specific IgG antibody titres (1 of 1280), measured by the indirect immunofluorescent (IIF) test, and two had Brucella melitensis isolated from their blood. In two cases, STCL arthritis was the presenting problem, and it was associated in one with ankle arthritis, hepatitis, renal impairment, orogenital ulcers and a haematological picture of myelodysplasia; in the other it was a relapsing STCL arthritis. In the remaining two cases, STCL arthritis was part of an extensive osteoarticular disease, which was associated in one with cachexia, liver cirrhosis, heart failure and prostatitis with urine retention, and in the other with severe thrombocytopenia. Excellent results were obtained from six to eight weeks' therapy with streptomycin, rifampicin and cotrimoxazole or tetracycline.

  10. Current concepts in the treatment of gouty arthritis.

    Science.gov (United States)

    Fang, Zhen-hua; Waizy, Hazibullah

    2013-02-01

    Gouty arthritis is an extremely painful condition that causes functional impairment. Gouty arthritis has become increasingly complex because of multiple comorbidities, iatrogenic factors and hyperuricemia that is refractory to treatment. In this review, we present a general overview of gouty arthritis including its pathophysiology, clinical presentations, diagnosis, predisposing factors and prophylactic therapy for preventing gouty arthritis flares.

  11. Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis.

    LENUS (Irish Health Repository)

    Aherne, Carol M

    2009-10-01

    Expression of the orphan nuclear receptor NR4A2 is controlled by pro-inflammatory mediators, suggesting that NR4A2 may contribute to pathological processes in the inflammatory lesion. This study identifies the chemoattractant protein, interleukin 8 (IL-8\\/CXCL8), as a molecular target of NR4A2 in human inflammatory arthritis and examines the mechanism through which NR4A2 modulates IL-8 expression. In TNF-alpha-activated human synoviocyte cells, enhanced expression of IL-8 mRNA and protein correspond to temporal changes in NR4A2 transcription and nuclear distribution. Ectopic expression of NR4A2 leads to robust changes in endogenous IL-8 mRNA levels and co-treatment with TNF-alpha results in significant (p<0.001) secretion of IL-8 protein. Transcriptional effects of NR4A2 on the human IL-8 promoter are enhanced in the presence of TNF-alpha, suggesting molecular crosstalk between TNF-alpha signalling and NR4A2. A dominant negative IkappaB kinase antagonizes the combined effects of NR4A2 and TNF-alpha on IL-8 promoter activity. Co-expression of NR4A2 and the p65 subunit of NF-kappaB enhances IL-8 transcription and functional studies indicate that transactivation occurs independently of NR4A2 binding to DNA or heterodimerization with additional nuclear receptors. The IL-8 minimal promoter region is sufficient to support NR4A2 and NF-kappaB\\/p65 co-operative activity and NR4A2 can interact with NF-kappaB\\/p65 on a 39bp sequence within this region. In patients treated with methotrexate for active inflammatory arthritis, a reduction in NR4A2 synovial tissue levels correlate significantly (n=10, r=0.73, p=0.002) with changes in IL-8 expression. Collectively, these data delineate an important role for NR4A2 in modulating IL-8 expression and reveal novel transcriptional responses to TNF-alpha in human inflammatory joint disease.

  12. 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.

  13. Cardiovascular involvement in psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    V. De Gennaro Colonna

    2011-11-01

    Full Text Available Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2-3% of the Caucasian population. A considerable proportion of these patients develop a form of inflammatory arthritis known as psoriatic arthritis (PsA, although the prevalence of this has not been well defined. Patients with PsA have a higher mortality rate than the general population and the risk of mortality is related to disease severity at the time of presentation. Endothelial dysfunction and early atherosclerosis have been found in patients with PsA without any cardiovascular disease (CVD risk factors, and experts believe that CVD is one of the leading causes of death, as it is in patients with rheumatoid arthritis (RA. Various disease-related mechanisms may be involved in the development of premature vascular damage in both cases, including an increased synthesis of proinflammatory mediators (such as cytokines, chemokines and adhesion molecules, autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress, abnormal vascular repair, and iatrogenic factors. In a recent study of 22 patients with PsA without any signs of CVD, we found that the plasma concentration of asymmetric dimethylarginine (ADMA levels were significantly high and coronary flow reserve (CFR was significantly reduced. Moreover, there was a significant correlation between CFR and plasma ADMA levels in the PsA group. The significant correlation between the reduced CRF and increased ADMA levels suggests that, like patients with early RA, PsA patients suffer from endothelial dysfunction and impaired coronary microcirculation. Active PsA is a risk factor for CVD, and so PsA patients should be screened for subclinical forms of the disease and its risk factors, and an early treatment approach should be adopted.

  14. IL-6 amplifies TLR mediated cytokine and chemokine production: implications for the pathogenesis of rheumatic inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Ivan Caiello

    Full Text Available The role of Interleukin(IL-6 in the pathogenesis of joint and systemic inflammation in rheumatoid arthritis (RA and systemic juvenile idiopathic arthritis (s-JIA has been clearly demonstrated. However, the mechanisms by which IL-6 contributes to the pathogenesis are not completely understood. This study investigates whether IL-6 affects, alone or upon toll like receptor (TLR ligand stimulation, the production of inflammatory cytokines and chemokines in human peripheral blood mononuclear cells (PBMCs, synovial fluid mononuclear cells from JIA patients (SFMCs and fibroblast-like synoviocytes from rheumatoid arthritis patients (RA synoviocytes and signalling pathways involved. PBMCs were pre-treated with IL-6 and soluble IL-6 Receptor (sIL-6R. SFMCs and RA synoviocytes were pre-treated with IL-6/sIL-6R or sIL-6R, alone or in combination with Tocilizumab (TCZ. Cells were stimulated with LPS, S100A8-9, poly(I-C, CpG, Pam2CSK4, MDP, IL-1β. Treatment of PBMCs with IL-6 induced production of TNF-α, CXCL8, and CCL2, but not IL-1β. Addition of IL-6 to the same cells after stimulation with poly(I-C, CpG, Pam2CSK4, and MDP induced a significant increase in IL-1β and CXCL8, but not TNF-α production compared with TLR ligands alone. This enhanced production of IL-1β and CXCL8 paralleled increased p65 NF-κB activation. In contrast, addition of IL-6 to PBMCs stimulated with LPS or S100A8-9 (TLR-4 ligands led to reduction of IL-1β, TNF-α and CXCL8 with reduced p65 NF-κB activation. IL-6/IL-1β co-stimulation increased CXCL8, CCL2 and IL-6 production. Addition of IL-6 to SFMCs stimulated with LPS or S100A8 increased CXCL8, CCL2 and IL-1β production. Treatment of RA synoviocytes with sIL-6R increased IL-6, CXCL8 and CCL2 production, with increased STAT3 and p65 NF-κB phosphorylation. Our results suggest that IL-6 amplifies TLR-induced inflammatory response. This effect may be relevant in the presence of high IL-6 and sIL-6R levels, such as in arthritic

  15. 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

  16. Psoriatic arthritis: genetics and pathogenesis

    Directory of Open Access Journals (Sweden)

    A. Mathieu

    2012-06-01

    Full Text Available Psoriatic arthritis is a complex disease affecting primarily peripheral and axial joints and entheses together with the skin. The pathogenesis is characterized by a genetic background and by inflammatory mechanisms which may be triggered by environmental factors. Several susceptibility genes have been investigated; they include HLA genes, genes within the HLA region and genes outside the HLA region. T cells, including the recently described subset Th17, are thought to play an important role in the acute and chronic phases of the disease. Some of these findings allowed novel therapeutic interventions or opened new promising approaches in treatment. The most relevant data of the literature are summarized and discussed.

  17. Glucocorticoids in juvenile idiopathic arthritis.

    Science.gov (United States)

    Malattia, Clara; Martini, Alberto

    2014-05-01

    Although the use of corticosteroids in juvenile idiopathic arthritis (JIA) is now much more limited owing to the availability of methotrexate and biological agents, there are clinical scenarios where it is still indicated. For example, corticosteroids may be indicated for intraarticular injections to prevent joint deformities, as a "bridge" drug to relieve symptoms in polyarticular disease while waiting for methotrexate and biologics to exert their full therapeutic effects, and in the treatment of chronic iridocyclitis, macrophage activation syndrome, and systemic JIA, although the advent of interleukin (IL)-1 and IL-6 blockers has greatly reduced the latter indication.

  18. Imaging of juvenile idiopathic arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Karl [Birmingham Children' s Hospital, Radiology Department, Birmingham (United Kingdom)

    2006-08-15

    Over the past decade there have been considerable changes in the classification and imaging of juvenile idiopathic arthritis (JIA). Radiology now has a considerable role in the management of JIA, the differential diagnosis, monitoring disease progression and detecting complications. The different imaging modalities available, their role and limitations are discussed in this article and the various disease features that the radiologist should be aware of are described. An approach to the imaging of the child with joint disease and in the monitoring of disease complications are also discussed. (orig.)

  19. SEPTIC ARTHRITIS OF THE HIP IN ADULTS: A RARE PRESENTATION

    Directory of Open Access Journals (Sweden)

    Kuppa

    2015-01-01

    Full Text Available Septic Arthritis also known as infectious arthritis, can be bacterial or fungal arthritis. The condition is an inflammation of a joint that is caused by an infection. Typically, Septic Arthritis affects one large joint in the body such as knee or hip. Generally, Septic Arthritis is present with complete absorption of the head of the Femur in infants. A case was encountered in which the complete absorption of the femoral head was seen in adults also

  20. [Relationship between periodontal disease and rheumatoid arthritis].

    Science.gov (United States)

    Zhang, Dai-zun; Zhong, De-yu; Deng, Jing; Wang, Ji-bo

    2005-12-01

    To study a population of rheumatoid arthritis patients and determine the extent of periodontal disease in these patients, in order to investigate the relationship between periodontal disease and rheumatoid arthritis. The experimental group was composed of 70 patients with rheumatoid arthritis and the control group consisted of 70 age- and gender-matched individuals without rheumatoid arthritis. The relationship between periodontal status in rheumatoid arthritis and control groups as well as the relationship between periodontal status and rheumatological findings in patients were analyzed. The percentage of periodontal disease was statistically significant between experimental and control group (P 0.05). There were more number of periodontal disease index 5 or 6 in experimental group than in control group ( P Rheumatoid arthritis patients with moderate to severe bone loss had deeper degree of morning stiffness, erythrocyte sedimentation rate levels and serum C-reactive protein levels than patients with no or mild bone loss. Individuals with rheumatoid arthritis are more likely to experience periodontal disease compares to healthy subjects. They are also very likely to suffer from moderate to severe periodontitis.

  1. Indirect costs of rheumatoid arthritis.

    Science.gov (United States)

    Raciborski, Filip; Kłak, Anna; Kwiatkowska, Brygida

    2015-01-01

    It is estimated that in Poland about 400,000 persons in general suffer from inflammatory joint diseases, including rheumatoid arthritis (RA). Epidemiological surveys documenting the frequency and disturbance of musculoskeletal disorders in the Polish population are few in number. Most of the estimations are based on epidemiological data from other countries (prevalence of 0.5-1%). According to the data of the National Health Fund in Poland 135,000-157,000 persons in total are treated because of rheumatoid arthritis per year [ICD10 (International Statistical Classification of Diseases and Related Health Problems): M05, M06]. In the case of this group of diseases indirect costs significantly outweigh the direct costs. Indirect costs increase together with activity level of the disease. The cost analysis of productivity loss of RA patients indicates that sickness absenteeism and informal care are the most burdensome. At the national level it amounts in total from 1.2 billion to 2.8 billion PLN per year, depending on the method of analysis. These costs could be significantly reduced through early diagnosis and introduction of effective treatment.

  2. Complementary medicine in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    F. Atzeni

    2011-09-01

    Full Text Available Use of complementary and alternative medicine (CAM for chronic conditions has increased in recent years. CAM is immensely popular for musculoskeletal conditions and patients suffering from rheumatoid arthritis (RA frequently try CAM. This review summarises the trial data for or against CAM as a symptomatic treatment for rheumatoid arthritis. Collectively the evidence demonstrates that some CAM modalities show significant promise, e.g. acupuncture, diets, herbal medicine, homoeopathy, massage, supplements. However, for the great majority of these therapies no evidencebased (clinical randomized trials results are available. CAM is usually used in addition to, and not as a substitute for conventional therapies. The motivation of patients to try CAM is complex; the willingness to take control of their healthcare, the desire to try everything available, the mass-media pressure and the erroneous notion that CAM is without risks. In fact, none of these treatments is totally devoid of risks. While the use of complementary and alternative modalities for the treatment of RA continues to increase, rigorous clinical trials examining their efficacy are needed before definitive recommendations regarding the application of these modalities can be made.

  3. 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.

  4. 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.

  5. Chronic Lyme disease arthritis: review of the literature and report of a case of wrist arthritis.

    Science.gov (United States)

    Scerpella, T A; Engber, W D

    1992-05-01

    A case of Lyme arthritis with advanced degenerative changes localized to the midcarpal joint was treated with a limited wrist arthrodesis with relief of pain and improved function. Chronic Lyme arthritis occurs as the third stage of Lyme disease. Serologic testing and a history of a characteristic rash may be helpful in the diagnosis. Radiographic and histopathologic findings are nonspecific, with both degenerative and inflammatory characteristics. Intravenous antibiotics provide an effective treatment of chronic Lyme arthritis.

  6. Chronic joint symptoms and prior arthritis diagnosis in community surveys: implications for arthritis prevalence estimates.

    OpenAIRE

    Feinglass, Joe; Nelson, Cynthia; Lawther, Timothy; Chang, Rowland W.

    2003-01-01

    OBJECTIVES: Alternative definitions of arthritis in community surveys provide very different estimates of arthritis prevalence among older Americans. This telephone interview study examines prevalence estimates based on the current Behavioral Risk Factor Surveillance System (BRFSS) arthritis case definition. METHODS: Interviews were conducted with 851 Chicago residents age 45 and older. Logistic regression was used to compare the age and sex controlled prevalence of poor health, restricted ac...

  7. Coexistence of Sarcoidosis and Gouty Arthritis.

    Science.gov (United States)

    Semiz, Hüseyin; Kobak, Senol

    2017-08-21

    Sarcoidosis is an inflammatory disease with unknown cause characterized by non-caseating granuloma formations. It may present with bilateral hilar lymphadenopathy, skin lesions, the involvement of eye and symptoms on the locomotor system. Gouty arthritis is an autoinflammatory disease characterized by hyperuricemia, recurrent arthritis attacks and the deposition of monosodium urate crystals in the joints and the surrounding tissues. We reported the coexistence of sarcoidosis and gouty arthritis in this paper. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  8. My Treatment Approach to Rheumatoid Arthritis

    Science.gov (United States)

    Davis, John M.; Matteson, Eric L.

    2012-01-01

    The past decade has brought important advances in the understanding of rheumatoid arthritis and its management and treatment. New classification criteria for rheumatoid arthritis, better definitions of treatment outcome and remission, and the introduction of biologic response-modifying drugs designed to inhibit the inflammatory process have greatly altered the approach to managing this disease. More aggressive management of rheumatoid arthritis early after diagnosis and throughout the course of the disease has resulted in improvement in patient functioning and quality of life, reduction in comorbid conditions, and enhanced survival. PMID:22766086

  9. Schizophrenia, rheumatoid arthritis and trytophan metabolism.

    Science.gov (United States)

    Taylor, W M

    1978-06-01

    Rheumatoid arthritis and schizophrenia have been described in early surveys as mutually exclusive disorders. Such claims are seen as especially interesting in view of: (1) indications that both illnesses often follow prodromes of severe psychological stress, (2) theories regarding hypermethylation of indoleamines producing endogenous psychotogens in schizophrenia, and (3) studies of rheumatoid arthritis reporting excessive binding of L-tryptophan to plasma protein, abnormalities of urinary tryptophan metabolites, decreased serotonin binding capacity of thrombocytes, and decreased MAO activity in joint fluid. Further comparative studies of tryptophan metabolism in schizophrenia and rheumatoid arthritis might enhance knowledge of pathogenesis in either or both diseases.

  10. Fungal arthritis of the wrist caused by Candida parapsilosis during infliximab therapy for rheumatoid arthritis.

    Science.gov (United States)

    Miyamoto, Hideaki; Miura, Toshiki; Morita, Euan; Morizaki, Yutaka; Uehara, Kosuke; Ohe, Takashi; Tanaka, Sakae

    2012-11-01

    A 60-year-old woman with rheumatoid arthritis, who had been treated with infliximab, presented with uncontrollable wrist arthritis. Fungal arthritis caused by Candida parapsilosis was confirmed by examining her aspirated joint fluid. Her infliximab therapy was interrupted, and antifungal therapy with fluconazole was started. After the fungal infection had been ameliorated, surgical debridement and arthrodesis of the wrist joint were conducted, and her symptoms completely resolved. Although fungal arthritis is rare, it should be considered as a differential diagnosis of exacerbated monoarthritis in patients treated with biological agents.

  11. 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.

  12. Rapidly progressing polyarticular septic arthritis in a patient with rheumatoid arthritis.

    Science.gov (United States)

    Dhaliwal, Sandeep; LeBel, Marie-Eve

    2012-07-01

    Septic arthritis is an orthopedic emergency that can lead to significant morbidity and mortality. Polyarticular involvement is a relatively rare phenomenon occurring primarily in high-risk patients. In this article, we report the rare case of a patient with rheumatoid arthritis presenting with an acute episode of septic arthritis involving most of the joints of the body. Surprisingly, his bilateral total hip arthroplasties were completely unaffected. Unusual polyarticular presentations of septic arthritis, though rare, must still be considered within the differential diagnosis by all healthcare providers when treating certain high-risk groups.

  13. 78 FR 36305 - Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Science.gov (United States)

    2013-06-17

    ... AFFAIRS Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune... Arthritis (including inflammatory, autoimmune, crystalline and infectious arthritis) and Dysbaric... inflammatory, autoimmune, crystalline and infectious arthritis) and Dysbaric Osteonecrosis Disability...

  14. 78 FR 65450 - Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Science.gov (United States)

    2013-10-31

    ... AFFAIRS Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune... (including inflammatory, autoimmune, crystalline and infectious arthritis) and Dysbaric Osteonecrosis...-Degenerative Arthritis (including inflammatory, autoimmune, crystalline and infectious arthritis) and...

  15. Vital Signs: Prevalence of Doctor-Diagnosed Arthritis and Arthritis-Attributable Activity Limitation - United States, 2013-2015.

    Science.gov (United States)

    Barbour, Kamil E; Helmick, Charles G; Boring, Michael; Brady, Teresa J

    2017-03-10

    In the United States, doctor-diagnosed arthritis is a common and disabling chronic condition. Arthritis can lead to severe joint pain and poor physical function, and it can negatively affect quality of life. CDC analyzed 2013-2015 data from the National Health Interview Survey, an annual, nationally representative, in-person interview survey of the health status and behaviors of the noninstitutionalized civilian U.S. adult population, to update previous prevalence estimates of arthritis and arthritis-attributable activity limitations. On average, during 2013-2015, 54.4 million (22.7%) adults had doctor-diagnosed arthritis, and 23.7 million (43.5% of those with arthritis) had arthritis-attributable activity limitations (an age-adjusted increase of approximately 20% in the proportion of adults with arthritis reporting activity limitations since 2002 [p-trend arthritis were 49.3%, 47.1%, and 30.6%, respectively; the prevalences of arthritis-attributable activity limitations among adults with these conditions and arthritis were 54.5% (heart disease), 54.0% (diabetes), and 49.0% (obesity). The prevalence of arthritis is high, particularly among adults with comorbid conditions, such as heart disease, diabetes, and obesity. Furthermore, the prevalence of arthritis-attributable activity limitations is high and increasing over time. Approximately half of adults with arthritis and heart disease, arthritis and diabetes, or arthritis and obesity are limited by their arthritis. Greater use of evidence-based physical activity and self-management education interventions can reduce pain and improve function and quality of life for adults with arthritis and also for adults with other chronic conditions who might be limited by their arthritis.

  16. Dietary interventions for rheumatoid arthritis.

    Science.gov (United States)

    Hagen, Kåre Birger; Byfuglien, Marte Gjeitung; Falzon, Louise; Olsen, Sissel Urke; Smedslund, Geir

    2009-01-21

    The question of what potential benefits and harms are associated with certain dietary regimes used in rheumatoid arthritis is an important one for many patients and health care providers. To assess the effectiveness and safety of dietary interventions in the treatment of rheumatoid arthritis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library, issue 1 2008), MEDLINE, EMBASE, AMED, CINAHL and reference lists of relevant articles (up to January 2008), and contacted authors of included articles. Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) where the effectiveness of dietary manipulation was evaluated. Dietary supplement studies (including fish oil supplements) were not included. Two authors independently selected trials for inclusion, assessed the internal validity of included trials and extracted data. Investigators were contacted to obtain missing information. Fourteen RCTs and one CCT, with a total of 837 patients, were included. Due to heterogeneity of interventions and outcomes, baseline imbalance and inadequate data reporting, no overall effects were calculated. A single trial with a moderate risk of bias found that fasting, followed by 13 months on a vegetarian diet, may reduce pain (mean difference (MD) on a 0 to 10 scale -1.89, 95% confidence interval (CI) -3.62 to -0.16), but not physical function or morning stiffness immediately after intervention. Another single trial with a moderate risk of bias found that a 12-week Cretan Mediterranean diet may reduce pain (MD on a 0 to 100 scale -14.00, 95% CI -23.6 to -4.37), but not physical function or morning stiffness immediately after intervention. Two trials compared a 4-week elemental diet with an ordinary diet and reported no significant differences in pain, function or stiffness. Due to inadequate data reporting, the effects of vegan and elimination diets are uncertain. When comparing any dietary manipulation with an ordinary diet we found

  17. Management of melioidosis osteomyelitis and septic arthritis.

    Science.gov (United States)

    Shetty, R P; Mathew, M; Smith, J; Morse, L P; Mehta, J A; Currie, B J

    2015-02-01

    Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis. We undertook a retrospective review of 50 patients with these conditions in an attempt to determine the effect of location of the disease, type of surgical intervention and duration of antibiotic treatment on outcome, particularly complications and relapse. We found that there was a 27.5% risk of osteomyelitis of the adjacent bone in patients with septic arthritis in the lower limb. Patients with septic arthritis and osteomyelitis of an adjacent bone were in hospital significantly longer (p = 0.001), needed more operations (p = 0.031) and had a significantly higher rate of complications and re-presentation (p = 0.048). More than half the patients (61%), most particularly those with multifocal bone and joint involvement, and those with septic arthritis and osteomyelitis of an adjacent bone who were treated operatively, needed more visits to theatre.

  18. Marine oil supplements for arthritis pain

    DEFF Research Database (Denmark)

    Senftleber, Ninna K.; Nielsen, Sabrina M.; Andersen, Jens Rikardt;

    2017-01-01

    Arthritis patients often take fish oil supplements to alleviate symptoms, but limited evidence exists regarding their efficacy. The objective was to evaluate whether marine oil supplements reduce pain and/or improve other clinical outcomes in patients with arthritis. Six databases were searched...... systematically (24 February 2015). We included randomized trials of oral supplements of all marine oils compared with a control in arthritis patients. The internal validity was assessed using the Cochrane Risk of Bias tool and heterogeneity was explored using restricted maximum of likelihood (REML)-based meta...... interval, CI, -0.42 to -0.07; heterogeneity, I2 = 63%. A significant effect was found in patients with rheumatoid arthritis (22 trials; -0.21; 95% CI, -0.42 to -0.004) and other or mixed diagnoses (3 trials; -0.63; 95% CI, -1.20 to -0.06), but not in osteoarthritis patients (5 trials; -0.17; 95% CI, -0...

  19. Role of Gut Microbiota in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Yuichi Maeda

    2017-06-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune disease, caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota, which is thought to be an environmental agent affecting the development of RA. Here we review the evidence from animal and human studies that supports the role of the gut microbiota in RA. We and others have demonstrated that the abundance of Prevotella copri is increased in some early RA. We have also used gnotobiotic experiments to show that dysbiosis in RA patients contributed to the development of Th17 cell-dependent arthritis in intestinal microbiota-humanized SKG mice. On the other hand, Prevotella histicola from human gut microbiota suppressed the development of arthritis. In summary, Prevotella species are involved in the pathogenesis of arthritis.

  20. Juvenile idiopathic arthritis and the temporomandibular joint ...

    African Journals Online (AJOL)

    ... resonance imaging findings of temporomandibular joint inflammation among juvenile ... The mean total MRI score was significantly higher in patients with active ... Clinical signs of TMJ arthritis can be used as filter for MRI examination TMJ is ...

  1. Marine oil supplements for arthritis pain

    DEFF Research Database (Denmark)

    Senftleber, Ninna K.; Nielsen, Sabrina M.; Andersen, Jens Rikardt

    2017-01-01

    Arthritis patients often take fish oil supplements to alleviate symptoms, but limited evidence exists regarding their efficacy. The objective was to evaluate whether marine oil supplements reduce pain and/or improve other clinical outcomes in patients with arthritis. Six databases were searched...... systematically (24 February 2015). We included randomized trials of oral supplements of all marine oils compared with a control in arthritis patients. The internal validity was assessed using the Cochrane Risk of Bias tool and heterogeneity was explored using restricted maximum of likelihood (REML)-based meta...... interval, CI, -0.42 to -0.07; heterogeneity, I2 = 63%. A significant effect was found in patients with rheumatoid arthritis (22 trials; -0.21; 95% CI, -0.42 to -0.004) and other or mixed diagnoses (3 trials; -0.63; 95% CI, -1.20 to -0.06), but not in osteoarthritis patients (5 trials; -0.17; 95% CI, -0...

  2. Arthritis Genetics Analysis Aids Drug Discovery

    Science.gov (United States)

    ... Matters NIH Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team ... may play a role in triggering the disease. Genetic factors are also thought to play a role. ...

  3. Total shoulder replacement in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Sneppen, O; Fruensgaard, S; Johannsen, Hans Viggo

    1996-01-01

    A prospective study of 62 Neer mark II total shoulder arthroplasties performed during the period from 1981 to 1990 on 51 patients with rheumatoid arthritis was undertaken to evaluate factors associated with component loosening and proximal humeral migration. Thirty-two (51%) showed proximal migra...... is recommended. Hemiarthroplasty with a cemented humeral prosthesis may be a better treatment in the end stage of rheumatoid arthritis of the shoulder.......A prospective study of 62 Neer mark II total shoulder arthroplasties performed during the period from 1981 to 1990 on 51 patients with rheumatoid arthritis was undertaken to evaluate factors associated with component loosening and proximal humeral migration. Thirty-two (51%) showed proximal......, range of movement, abduction force, or function. The risk of clinical asymptomatic loosening is a relatively late complication that is eventually followed by pronounced bone destruction related to the loose component. Long-term radiographic control of total shoulders with rheumatoid arthritis...

  4. immunological arthritis Prevalence of biochemical and abnormalities ...

    African Journals Online (AJOL)

    1991-02-02

    Feb 2, 1991 ... immunological abnormalities noted were a positive rheumatoid factor (78,9%), positive ... Rheumatoid arthritis (RA) is a systemic disease characterised by the occurrence of articular and ..... treatment. Br Med] 1982; 285: ...

  5. Juvenile idiopathic arthritis and the temporomandibular joint

    African Journals Online (AJOL)

    Yasser Mohammed

    2012-02-01

    Feb 1, 2012 ... a Radiology, Ain Shams University hospitals, Faculty of Medicine, Ain Shams University, Cairo, .... pacemakers, metal implants or dental braces were excluded .... Patients with JIA are at high risk of developing arthritis of the.

  6. SIGNIFICANCE OF PERIPHERAL ARTHRITIS IN ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    Sh. F. Erdes

    2014-01-01

    Full Text Available Objective: to elucidate the role of peripheral arthritis in ankylosing spondylitis (AS and its impact on therapy choice in daily practice of rheumatologists. Subjects and methods. The investigation enrolled 330 consecutive patients with AS referred to rheumatologists during 4 months in 24 cities and towns of the Russian Federation. A specially designed clinical schedule was filled out for all the patients. Results. Peripheral arthritis was present in 47% of patients, including in 17 and 46% who had upper and lower limb joint involvement, respectively. Patients with peripheral arthritis had higher ESR, BASDAI and ASDAS-ESR levels. They were also found to have more marked functional disorders than the patients with its isolated axial variant. The clinical signs of hip joint involvement were detected in 56% of the patients and they were bilateral in 43%. In the rheumatologists' opinion, 24 (8% needed total hip joint replacement. Conclusion. Peripheral arthritis aggravates AS.

  7. Tips and tricks to recognize microcrystalline arthritis

    National Research Council Canada - National Science Library

    Filippucci, Emilio; Di Geso, Luca; Grassi, Walter

    2012-01-01

    .... The knowledge of some tips and tricks in the identification of these findings can play a key role in exploiting the relevant potential of US in microcrystalline arthritis, avoiding errors and misinterpretations...

  8. Rheumatoid Arthritis and Periodontal Disease. An Update

    National Research Council Canada - National Science Library

    Venkataraman, Archana; Almas, Khalid

    2015-01-01

    ...: 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...

  9. Innovative medicines for treatment of psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Levitan A.l.

    2015-09-01

    Full Text Available The problem of effective treatment of psoriatic arthritis has not been solved yet. The search for new therapeutic options is very active in many directions. At the stage of clinical trials are drugs that block interleukin-17-a (secukinumab, ixekizumab, brodalumab, drugs that suppress interleukin-12 and interleukin-23 (ustekinumab. To modern means to ensure psoriatic arthritis include drugs that are inhibitors of small molecules orkinase pathways (apremilast, tofacitinib.

  10. Tips and tricks to recognize microcrystalline arthritis.

    Science.gov (United States)

    Filippucci, Emilio; Di Geso, Luca; Grassi, Walter

    2012-12-01

    US plays a useful role in diagnosing and monitoring therapy in microcrystalline arthritis, as it may detect both monosodium urate and calcium pyrophosphate crystal aggregates. The knowledge of some tips and tricks in the identification of these findings can play a key role in exploiting the relevant potential of US in microcrystalline arthritis, avoiding errors and misinterpretations. This review provides an in-depth description of simple technical and methodological issues to guide the rheumatologist in daily clinical practice.

  11. Pathogenesis and Prediction of Future Rheumatoid Arthritis

    Science.gov (United States)

    2014-10-01

    AWARD NUMBER: W81XWH-13-1-0408 TITLE: Pathogenesis and Prediction of Future Rheumatoid Arthritis...5a. CONTRACT NUMBER Pathogenesis and Prediction of Future Rheumatoid Arthritis 5b. GRANT NUMBER W81XWH-13-1-0408 5c... pathogenesis of RA that can ultimately be targeted to prevent RA. This project has proposed to use a unique set of serum samples and clinical data

  12. 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.

  13. ▼ Apremilast for psoriasis and psoriatic arthritis.

    Science.gov (United States)

    2015-09-01

    ▼ Apremilast (Otezla - Celgene Europe Ltd.) is a novel orally administered immunomodulatory medicine licensed for the treatment of plaque psoriasis and psoriatic arthritis. The company suggests that it has demonstrated proven and durable efficacy in both conditions and has a favourable safety profile with no requirement for drug-specific pre-screening or ongoing laboratory monitoring. Here we review the evidence on the safety and efficacy of apremilast in the management of psoriasis and psoriatic arthritis.

  14. [Septic arthritis of thoracic facet joint].

    Science.gov (United States)

    Ben Abdelghani, K; Gérard-Dran, D; Combe, B

    2009-08-01

    Septic arthritis of the facet joint is a rare condition. We report a case of septic arthritis of both a thoracic facet joint and a wrist. Clinical manifestations were consistent with a spondylodiscitis. Magnetic resonance imaging of the spine demonstrated infection of facet joints of T1 and T2. A surgical biopsy of the wrist isolated a type B streptococcus. The same organism was found in urine culture. The patient had an uneventful recovery on antibiotics.

  15. Juvenile idiopathic arthritis: how can the radiologist help the clinician?

    Energy Technology Data Exchange (ETDEWEB)

    Azouz, E.M. [Children' s Hospital of Eastern Ontario, Radiology Department, Ottawa, ON (Canada)

    2008-06-15

    The classification of the International League of Associations for Rheumatology (ILAR) is based on clinical criteria and includes: 1. Systemic arthritis 2. Oligoarthritis 3. Polyarthritis, rheumatoid factor positive 4. Polyarthritis, rheumatoid factor negative 5. Enthesitis-related arthritis 6. Psoriatic arthritis 7. Undifferentiated arthritis. Systematic arthritis is different from the other arthritides. It is associated with fever, rash, hepatosplenomegaly and lymphadenopathy. The arthritis is polyarticular and symmetrical. The enlarged liver, spleen and lymph nodes may be detected and followed clinically and, more accurately, with the help of cross-sectional imaging modality such as US or MRI. CT should be avoided in children because of the ionizing radiation. (orig.)

  16. [Effect of periodontal treatment on rheumatoid arthritis and vice versa].

    Science.gov (United States)

    de Smit, M J; Brouwer, E; Westra, J; Nesse, W; Vissink, A; van Winkelhoff, A J

    2012-04-01

    The pathogenesis of periodontitis and of rheumatoid arthritis show remarkable similarities. There is a distinct degree of co-existence between the 2 diseases. The prevalence of periodontitis is more pronounced in rheumatoid arthritis patients and the prevalence of rheumatoid arthritis is more pronounced in periodontitis patients. At present, a positive influence of periodontal treatment on the rheumatoid arthritis disease activity or of rheumatoid arthritis drug treatment on periodontitis is not sufficiently supported by clinical research. Periodontitis may play a role in unsatisfactory therapy response in some rheumatoid arthritis patients.

  17. [Team management of rheumatoid arthritis].

    Science.gov (United States)

    Le Loët, X; Vittecoq, O

    2001-12-01

    The main objectives of team management of rheumatoid arthritis are to stop structural damage of joints and to reduce functional, psychological, socioprofessional and economic consequences. Team management requires the collaboration, around the patient, of a rheumatologist, a nurse, a psychologist, a physiotherapist, an occupational therapist, an orthopaedic surgeon at the same time, in the same place. More and more patients wish to manage their disease by themselves. Team care should not be proposed to every patient; it must be reserved to patients whose condition required such an approach because of the severity of the disease, comorbidity, psychological or socioprofessionnal difficulties. Team management should be personalized. Utility of team management is now accepted; out-patient administration is as effective as in-patient one. A good educational program is very important. However, search is still needed to define optimal modalities of team management and tools to measure the efficiency of this approach.

  18. Rheumatoid arthritis affecting temporomandibular joint.

    Science.gov (United States)

    Sodhi, Amandeep; Naik, Shobha; Pai, Anuradha; Anuradha, Ardra

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory disorder that is characterized by joint inflammation, erosive properties and symmetric multiple joint involvement. Temporomandibular joint (TMJ) is very rare to be affected in the early phase of the disease, thus posing diagnostic challenges for the dentist. Conventional radiographs fail to show the early lesions due to its limitations. More recently cone-beam computed tomography (CBCT) has been found to diagnose the early degenerative changes of TMJ and hence aid in the diagnosis of the lesions more accurately. Our case highlights the involvement of TMJ in RA and the role of advanced imaging (CBCT) in diagnosing the bony changes in the early phase of the disease.

  19. Collagen Biomarkers for Arthritis Applications

    Directory of Open Access Journals (Sweden)

    James D. Birmingham

    2006-01-01

    Full Text Available The most common form of chronic arthritis is osteoarthritis (OA with prevalence as high as 80% after age 75 (Arden and Nevitt, 2006. The incidence of OA is expected to increase as the population ages, increasing the socioeconomic burden of OA. Despite the signifi cant burden of this disease, no drug has been identifi ed that can effectively modify disease progression (Moskowitz and Hooper, 2005; Abadie et al. 2004. However, slowing disease progress and improvement in quality of life may be achieved by behavioral modifi cations, such as weight loss and exercise. Many patients with early OA will progress to disability and joint replacement. Physical examination and radiographic studies are relatively poor means for detecting disease early or predicting progression. Therefore, identifi cation of factors to facilitate early OA diagnosis and prognosis is a major focus of current OA research (Lohmander and Felson, 2004; Lohmander, 2004; Garnero and Delmas, 2003.

  20. Rheumatoid arthritis affecting temporomandibular joint

    Directory of Open Access Journals (Sweden)

    Amandeep Sodhi

    2015-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic, systemic, autoimmune inflammatory disorder that is characterized by joint inflammation, erosive properties and symmetric multiple joint involvement. Temporomandibular joint (TMJ is very rare to be affected in the early phase of the disease, thus posing diagnostic challenges for the dentist. Conventional radiographs fail to show the early lesions due to its limitations. More recently cone-beam computed tomography (CBCT has been found to diagnose the early degenerative changes of TMJ and hence aid in the diagnosis of the lesions more accurately. Our case highlights the involvement of TMJ in RA and the role of advanced imaging (CBCT in diagnosing the bony changes in the early phase of the disease.

  1. Treatment of acute septic arthritis.

    Science.gov (United States)

    Pääkkönen, Markus; Peltola, Heikki

    2013-06-01

    Acute septic arthritis is a rare, but potentially devastating disease. The treatment is initiated intravenously, but can be safely switched to oral after 2-4 days providing large doses of a well-absorbing antibiotic and, for time-dependent antibiotics, 4 times-a-day administration are used. Empiric treatment should always cover Staphylococcus aureus and common respiratory pathogens, whereas Kingella kingae and Salmonella are important only regionally. Studies conducted by our group have shown that a total course of 10 days may suffice for previously healthy children in a Western setting. Treatment of neonates, patients with immunodeficiency or cases caused by methicillin-resistant S. aureus, may deserve a different approach.

  2. [Pulmonary manifestations in rheumatoid arthritis].

    Science.gov (United States)

    Morawska, Justyna; Domysławska, Izabela; Bagrowska, Magdalena; Sierakowski, Stanislaw

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destructive cartilages, bones and other structures formed joints. RA belongs to connective tissue diseases represented by systemic nature, internal illness, extra-articular features and rapidly progress of atherosceirosis. The extra-articular complications cause the reduction of patient longevity. The frequency of symptoms in patient with RA and respiratory disorders occur in 10-20% of cases. Pulmonary complications are the second most common cause of premature of patient deaths. Respiratory disorders associated with RA are devided into 3 groups: infection, lung disease caused by drugs and pulmonary manifestation connected by RA. These last affect interstitial tissue, bronchioli, pulmonary vessels, pleura, also are presented by pulmonary rheumatoid nodules and pulmonary hypertension.

  3. Nail abnormalities in rheumatoid arthritis.

    Science.gov (United States)

    Michel, C; Cribier, B; Sibilia, J; Kuntz, J L; Grosshans, E

    1997-12-01

    Many nail abnormalities have traditionally been described in association with rheumatoid arthritis (RA), but their specificity has never been assessed in a controlled study. Our purpose was to evaluate the frequency and the specificity of nail changes associated with RA in a case-controlled study including 50 patients suffering from RA and 50 controls. For each patient, a general skin examination was performed and the 20 nails were examined. The nail features were noted and classified. A chi 2 test or a Fisher test was used to compare the two groups. The only nail abnormalities significantly associated with RA were longitudinal ridging on nine or 10 finger nails (29 patients in the RA group vs. three in the controls, chi 2: P nail (24 patients vs. 10, chi 2: P nail changes were noticed but were not frequent enough to be significant. The presence of longitudinal ridging on the finger nails was significantly associated with RA.

  4. [New therapies for rheumatoid arthritis].

    Science.gov (United States)

    Salgado, Eva; Maneiro, José Ramón

    2014-11-18

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage and bone. Advances in the knowledge of disease pathogenesis allowed the identification of novel therapeutic targets such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6 or the system JAK/STAT phosphorylation. At present there are 5 TNF antagonists approved for RA. Tocilizumab blocks the pathway of IL-6 and is the only biological with proven efficacy in monotherapy. Rituximab modulates B cell response in RA. Abatacept provided new data on T cell involvement in the pathogenesis of RA. Tofacitinib is the first kinase inhibitor approved for this disease. Biologic drugs have proven efficacy, almost always in combination with methotrexate, and even halt radiographic progression. Monitoring infection is the main precaution in handling these patients. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  5. [Physiotherapy for juvenile idiopathic arthritis].

    Science.gov (United States)

    Spamer, M; Georgi, M; Häfner, R; Händel, H; König, M; Haas, J-P

    2012-07-01

    Control of disease activity and recovery of function are major issues in the treatment of children and adolescents suffering from juvenile idiopathic arthritis (JIA). Functional therapies including physiotherapy are important components in the multidisciplinary teamwork and each phase of the disease requires different strategies. While in the active phase of the disease pain alleviation is the main focus, the inactive phase requires strategies for improving motility and function. During remission the aim is to regain general fitness by sports activities. These phase adapted strategies must be individually designed and usually require a combination of different measures including physiotherapy, occupational therapy, massage as well as other physical procedures and sport therapy. There are only few controlled studies investigating the effectiveness of physical therapies in JIA and many strategies are derived from long-standing experience. New results from physiology and sport sciences have contributed to the development in recent years. This report summarizes the basics and main strategies of physical therapy in JIA.

  6. Burden of childhood-onset arthritis

    Directory of Open Access Journals (Sweden)

    Hassett Afton L

    2010-07-01

    Full Text Available Abstract Juvenile arthritis comprises a variety of chronic inflammatory diseases causing erosive arthritis in children, often progressing to disability. These children experience functional impairment due to joint and back pain, heel pain, swelling of joints and morning stiffness, contractures, pain, and anterior uveitis leading to blindness. As children who have juvenile arthritis reach adulthood, they face possible continuing disease activity, medication-associated morbidity, and life-long disability and risk for emotional and social dysfunction. In this article we will review the burden of juvenile arthritis for the patient and society and focus on the following areas: patient disability; visual outcome; other medical complications; physical activity; impact on HRQOL; emotional impact; pain and coping; ambulatory visits, hospitalizations and mortality; economic impact; burden on caregivers; transition issues; educational occupational outcomes, and sexuality. The extent of impact on the various aspects of the patients', families' and society's functioning is clear from the existing literature. Juvenile arthritis imposes a significant burden on different spheres of the patients', caregivers' and family's life. In addition, it imposes a societal burden of significant health care costs and utilization. Juvenile arthritis affects health-related quality of life, physical function and visual outcome of children and impacts functioning in school and home. Effective, well-designed and appropriately tailored interventions are required to improve transitioning to adult care, encourage future vocation/occupation, enhance school function and minimize burden on costs.

  7. Childhood Arthritis: Rate of Different Types

    Directory of Open Access Journals (Sweden)

    Karambin Mohammad Mehdi

    2009-04-01

    Full Text Available To determine the rate of different types of arthritis in children. We prepared a retrospective descriptive study and included the whole 100 cases of arthritis referred to 17-Shahrivar Hospital, Rasht, Guilan during a 3 years period. Using their medical files, data including age, sex, season of admission, history of trauma, signs and symptoms, lab findings and duration of hospitalization were collected. SPSS 13.0 (statistical software applied for statistical analysis. The most common age of involvement ranged 6-9 years. Septic arthritis, brucellosis, and rheumatoid fever were the most frequent causes of arthritis in our study. Fever and restricted range of motion had the highest rate among different signs and symptoms. Lab data demonstrated leukocytosis, positive CRP, and increased ESR among 74, 79.5, and 73 percent of our patients, respectively. According to the high prevalence of septic arthritis and the arthritis due to brucellosis and rheumatoid fever, it seems that mentioned diseases are still major problems in the issue of hygiene management.

  8. Arthritis

    Science.gov (United States)

    ... vegetables, which contain important vitamins and minerals, especially vitamin E. Eat foods rich in omega-3 fatty acids, such as cold water fish (salmon, mackerel, and herring), flaxseed, rapeseed (canola) oil, soybeans, ...

  9. Why golimumab in the treatment of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis?

    Directory of Open Access Journals (Sweden)

    M. Rossini

    2015-03-01

    Full Text Available Golimumab is an anti-TNF monoclonal antibody administred subcutaneously once a month and produced with an innovative technology that minimizes immunogenicity. This paper reviews and updates the main studies on the efficacy, safety and pharmacoeconomic aspects of treatment with golimumab of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis.

  10. Bilateral Cricoarytenoid Arthritis: A Cause of Recurrent Upper Airway Obstruction in Rheumatoid Arthritis

    OpenAIRE

    Pradhan, Pradeep; Bhardwaj, Abhishek; Venkatachalam, VP

    2016-01-01

    We report a case of bilateral cricoarytenoid joint arthritis with history of rheumatoid arthritis, presented with stridor to the outpatient department. Endolaryngoscopy revealed adducted vocal cords and a nodule over left arytenoid which later confirmed to be rheumatoid nodule on histopathologic examination. Initially, although patient responded well to medical treatment, recurrence was noticed after 6 months follow-up.

  11. 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.

  12. Isolated Arthritis of the Temporomandibular Joint as the Initial Manifestation of Juvenile Idiopathic Arthritis

    DEFF Research Database (Denmark)

    Hügle, Boris; Spiegel, Lynn; Hotte, Julia

    2017-01-01

    . Demographic and clinical data were analyzed using descriptive statistics. RESULTS: Fifty-five patients were identified (65% bilateral presentation). Six patients developed arthritis in other joints (median time 6 mos); 4 patients developed uveitis, all prior to arthritis. At last followup, 9% were still...

  13. Psoriatic arthritis mutilans (PAM) in the Nordic countries

    DEFF Research Database (Denmark)

    Gudbjornsson, B; Ejstrup, L; Gran, J T

    2013-01-01

    To determine the prevalence and clinical characteristics of psoriatic arthritis mutilans (PAM) in the Nordic countries.......To determine the prevalence and clinical characteristics of psoriatic arthritis mutilans (PAM) in the Nordic countries....

  14. Temporomandibular disorders in patients with rheumatoid arthritis: A ...

    African Journals Online (AJOL)

    2015-06-05

    Jun 5, 2015 ... depression (DEP) and nonspecific physical symptoms. (NPS).[3,15] ..... temporomandibular joint: prevalence, systemic therapy. Oral Maxillofac ... rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. A clinical.

  15. Elevated rheumatoid factor and long term risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Schnohr, Peter;

    2012-01-01

    To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.......To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis....

  16. Risk of atrial fibrillation and stroke in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Lindhardsen, Jesper; Ahlehoff, Ole; Gislason, Gunnar Hilmar;

    2012-01-01

    To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke.......To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke....

  17. Certain Jobs Linked to Raised Risk of Rheumatoid Arthritis

    Science.gov (United States)

    ... Certain Jobs Linked to Raised Risk of Rheumatoid Arthritis Risk was doubled among men who did electrical ... 2017 THURSDAY, Aug. 10, 2017 (HealthDay News) -- Rheumatoid arthritis, a painful disease in which a person's immune ...

  18. Degenerative Changes in the Spine: Is This Arthritis?

    Science.gov (United States)

    ... in my spine. Does this mean I have arthritis? Answers from April Chang-Miller, M.D. Yes. ... spine. Osteoarthritis is the most common form of arthritis. Doctors may also refer to it as degenerative ...

  19. What Are Osteoporosis and Arthritis and How Are They Different?

    Science.gov (United States)

    ... Home Osteoporosis Osteoporosis and Other Conditions What Are Osteoporosis and Arthritis and How Are They Different? Fast ... and Arthritis Cope? What About Pain? What Is Osteoporosis? Osteoporosis is a disease that makes bones weak ...

  20. Moraxella infectious arthritis: first report in an adult.

    OpenAIRE

    Rosenbaum, J; Lieberman, D. H.; Katz, W A

    1980-01-01

    The first occurrence of septic arthritis due to moraxella in an adult is reported. The clinical presentation mimicked disseminated gonococcaemia with associated gonococcal arthritis except for an atypical rash. Diagnosis was made by culture.

  1. Could a Germ Link Gum Disease, Rheumatoid Arthritis?

    Science.gov (United States)

    ... 162571.html Could a Germ Link Gum Disease, Rheumatoid Arthritis? Study may offer new insight into the cause ... the long-noticed connection between gum disease and rheumatoid arthritis, a new study suggests. The discovery might also ...

  2. Rheumatoid Arthritis Pain: Tips for Protecting Your Joints

    Science.gov (United States)

    Rheumatoid arthritis pain: Tips for protecting your joints Use these joint protection techniques to help you stay in control of your rheumatoid arthritis pain. By Mayo Clinic Staff Joint protection is ...

  3. Septic arthritis in the central part of Denmark

    DEFF Research Database (Denmark)

    Asmussen Andreasen, Rikke; Andersen, Nanna Skaarup; Just, Søren Andreas;

    Septic arthritis in the central part of Denmark, Annals of the Rheumatic Diseases, volume 73, supplement 2, p. 287......Septic arthritis in the central part of Denmark, Annals of the Rheumatic Diseases, volume 73, supplement 2, p. 287...

  4. Obesity May Make Rheumatoid Arthritis Tough to Spot, Track

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_164558.html Obesity May Make Rheumatoid Arthritis Tough to Spot, Track ... monitor rheumatoid arthritis may be thrown off by obesity in women, a new study suggests. "Physicians might ...

  5. Osteoporosis and Arthritis: Two Common but Different Conditions

    Science.gov (United States)

    ... your browser. Home Osteoporosis Osteoporosis and Other Conditions Osteoporosis and Arthritis: Two Common but Different Conditions Publication ... between these conditions. Osteoporosis Arthritis For Your Information Osteoporosis Osteoporosis is a condition in which the bones ...

  6. Inter- relationship between rheumatoid arthritis and periodontitis.

    Science.gov (United States)

    Rajkarnikar, J; Thomas, B S; Rao, S K

    2013-01-01

    Periodontal medicine defines a rapidly emerging branch of Periodontology focusing on establishing a strong relationship between periodontal health and systemic health. It is speculated that the major common dysregulation which links Periodontitis with Rheumatoid arthritis (RA) is being played by the mediators of immune inflammatory response. To determine whether there is any relationship between periodontal disease and Rheumatoid arthritis. A total of 100 patients were included for the present study which was divided into two groups: one group (cases) included 50 patients attending the Department of Orthopedics, Kasturba Medical College, Manipal who were diagnosed of Rheumatoid arthritis. Another subject population included 50 patients as controls attending the Department of Oral Medicine, Manipal College of Dental Sciences, Manipal with age and gender matched with those of rheumatoid arthritis group. Specific measures for periodontitis included plaque index, gingival index, number of missing teeth, and radiographic alveolar bone loss scores. Measures of rheumatoid arthritis included health assessment questionaires, levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Various periodontal parameters were compared between the cases and controls. The average alveolar bone loss was statistically more severe in Rheumatoid arthritis (RA) group than in the controls although there were similar plaque index in both the groups. The gingival index was statistically higher in the RA group. The Erythrocyte Sedimentation Rate (ESR) and C- Reactive Protein (CRP) levels of RA patients were also significantly associated with the severity of periodontal disease. There was a significant association between Rheumatoid arthritis and Periodontitis which may be due to a common underlying deregulation of the inflammatory response in these individuals.

  7. JUVENILE CHRONIC ARTHRITIS WITH EYE LESION

    Directory of Open Access Journals (Sweden)

    S O Salugina

    2002-01-01

    Full Text Available A bstract. Objective, to describe a series of pts with JRA/JCA and uveitis. Material and methods. The study included 81 pts with JRA and uveitis. There were 68 girls-84%, 13 boys-16%. We studied the clinical manifestations, the antinuclear antibodies (ANA using HEP-2 cells for the 33 pts with uveitis and 46 pts without uveitis, HLA status was determined for 36 pts. Results. 85,2% of the children had arthritis before uveitis. The mean age at onset of arthritis was 3,5 year (range: 1-10 yrs, the mean age at onset of uveitis was 6 year (range: 2-15 yrs. The mean interval between the onset of arthritis and uveitis was 3,02 years (range: 3,5 yrs before arthritis onset to 12,5 yrs after. In 68,1% pts the diagnosis of uveitis was made within 5 yrs after onset of arthritis. 93% of pts had mono-oligoarticular onset, but 50% had poliarticular course. 23,5% of pts had functional disability 3-4 classes. Ocular complications were developed in 53.1%: cataracts-38,3%, band keratopathy-11,1%, glaucoma-2,5%. 93,9% of 33 studied children with arthritis and uveitis were ANA positive, 9,1% were RF positive. 18,1 % had HLA-DR8 (p<0,001, 83,3% - HLA-A2 (p<0,00l, HLA-B27 - 30,6 % (p<0,00l. Conclusion. Clinical and laboratory data of our pts suggest that: lthe combination of arthritis and uveitis would be named JCA with uveitis; 2 according our opinion JCA with uveitis is separate nosological form among the juvenile arthritides.

  8. Pseudoseptic pseudogout in progressive pseudorheumatoid arthritis of childhood.

    OpenAIRE

    Bradley, J D

    1987-01-01

    Progressive pseudorheumatoid arthritis of childhood is an uncommon arthropathy of unknown aetiology, which is related to spondyloepiphyseal dysplasia tarda. Previous reports have noted the absence of joint inflammation in this disease. An adult is described here with this arthropathy, who developed episodic acute inflammatory arthritis that mimicked septic arthritis, but proved to be pseudogout. The relation between pseudogout and progressive pseudorheumatoid arthritis of childhood is discussed.

  9. Laboratory findings in psoriatic arthritis.

    Science.gov (United States)

    Punzi, L; Podswiadek, M; Oliviero, F; Lonigro, A; Modesti, V; Ramonda, R; Todesco, S

    2007-01-01

    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 (anti-TNF-alpha agents and the demonstration of their efficacy in the management of many clinical disease expressions including peripheral arthropathy, axial involvement, enthesopathy and skin manifestations, have stimulated

  10. Juvenile rheumatoid arthritis: therapeutic perspectives.

    Science.gov (United States)

    Chikanza, Ian C

    2002-01-01

    Juvenile rheumatoid arthritis (JRA) is the most common childhood chronic systemic autoimmune inflammatory disease. The therapeutic approach to JRA has, to date, been casual and based on extensions of clinical experiences gained in the management of adult rheumatoid arthritis (RA). The physiology of inflammation has been systemically studied and this has led to the identification of specific therapeutic targets and the development of novel approaches to the management of JRA. The classical treatments of the disease such as methotrexate, sodium aurothiomalate and sulfasalazine, are not always effective in controlling RA and JRA. This has necessitated the development of novel agents for treating RA, most of which are biological in nature and are targeted at specific sites of the inflammatory cascades. These biological therapeutic strategies in RA have proved successful and are being applied in the management of JRA. These developments have been facilitated by the advances in molecular biology which have heralded the advent of biodrugs (recombinant proteins) and gene therapy, in which specific genes can be introduced locally to enhance in vivo gene expression or suppress gene(s) of interest with a view to down-regulating inflammation. Some of these biodrugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), monoclonal antibodies (infliximab, adalimumab), TNF soluble receptor constructs (etanercept) and interleukin-1 receptor antagonist (IL-1Ra) have been tested and shown to be effective in RA. Etanercept has now been licensed for JRA. Clinical trials of infliximab in JRA are planned. Studies show that the clinical effects are transient, necessitating repeated treatments and the risk of vaccination effects. Anti-inflammatory cytokines such as IL-4, IL-10, transforming growth factor-beta and interferon-beta (IFN-beta) are undergoing clinical trials. Many of these agents have to be administered parenterally and production costs are very high; thus, there is a need

  11. Cytokine profiles in peripheral blood and whole blood cell cultures associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis

    DEFF Research Database (Denmark)

    Poulsen, Anne Havemose; Sørensen, Lars Korsbaek; Stoltze, Kaj

    2005-01-01

    Cytokines play a key role in the pathogenesis of inflammatory diseases. An obvious question is whether patients with aggressive periodontitis, juvenile idiopathic arthritis, or rheumatoid arthritis share blood cytokine profiles distinguishing them from individuals free of disease....

  12. Cytokine profiles in peripheral blood and whole blood cell cultures associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis

    DEFF Research Database (Denmark)

    Poulsen, Anne Havemose; Sørensen, Lars Korsbaek; Stoltze, Kaj

    2005-01-01

    Cytokines play a key role in the pathogenesis of inflammatory diseases. An obvious question is whether patients with aggressive periodontitis, juvenile idiopathic arthritis, or rheumatoid arthritis share blood cytokine profiles distinguishing them from individuals free of disease....

  13. 78 FR 32403 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-05-30

    ... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice and... meeting. Agenda: On July 22, 2013, the committee will discuss the Assessment of SpondyloArthritis...

  14. 77 FR 14529 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-03-12

    ... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice and... moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease...

  15. 38 CFR 4.58 - Arthritis due to strain.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Arthritis due to strain... FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.58 Arthritis due to strain. With service incurred lower extremity amputation or shortening, a disabling arthritis, developing in...

  16. 76 FR 29767 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-05-23

    ... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice and... arthritis attacks. ILARIS has also been shown to extend the time to the next attack and reduce the frequency...

  17. Molecular targets in arthritis and recent trends in nanotherapy.

    Science.gov (United States)

    Roy, Kislay; Kanwar, Rupinder Kaur; Kanwar, Jagat Rakesh

    2015-01-01

    Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

  18. Kingella kingae causing septic arthritis in Felty's syndrome.

    Science.gov (United States)

    Lewis, D A; Settas, L

    1983-08-01

    A case of septic arthritis of the elbow caused by Kingella kingae, a Gram-negative bacillus, is described. The patient had long-standing, severe rheumatoid arthritis and Felty's syndrome. This appears to be the first report from the United Kingdom of Kingella kingae as the aetiological agent of septic arthritis.

  19. Kingella kingae causing septic arthritis in Felty's syndrome.

    OpenAIRE

    Lewis, D A; Settas, L

    1983-01-01

    A case of septic arthritis of the elbow caused by Kingella kingae, a Gram-negative bacillus, is described. The patient had long-standing, severe rheumatoid arthritis and Felty's syndrome. This appears to be the first report from the United Kingdom of Kingella kingae as the aetiological agent of septic arthritis.

  20. Novel treatment strategies in rheumatoid arthritis.

    Science.gov (United States)

    Burmester, Gerd R; Pope, Janet E

    2017-06-10

    New treatment strategies have substantially changed the course of rheumatoid arthritis. Many patients can achieve remission if the disease is recognised early and is treated promptly and continuously; however, some individuals do not respond adequately to treatment. Rapid diagnosis and a treat-to-target approach with tight monitoring and control, can increase the likelihood of remission in patients with rheumatoid arthritis. In this Series paper, we describe new insights into the management of rheumatoid arthritis with targeted therapy approaches using classic and novel medications, and outline the potential effects of precision medicine in this challenging disease. Articles are included that investigate the treat-to-target approach, which includes adding or de-escalating treatment. Rheumatoid arthritis treatment is impeded by delayed diagnosis, problematic access to specialists, and difficulties adhering to treat-to-target principles. Clinical management goals in rheumatoid arthritis include enabling rapid access to optimum diagnosis and care and the well informed use of multiple treatments approved for this disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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.

  2. Cytokines in rheumatoid arthritis and osteoarthrosis

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    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. .

  3. Rheumatoid arthritis of the shoulder

    Energy Technology Data Exchange (ETDEWEB)

    Dijkstra, J.; Dijkstra, P.F.; Klundert, W. v. d.

    1985-02-01

    The course of rheumatoid arthritis in the shoulder is evaluated in 143 patients. In a period of 29 years, 630 X-rays were taken of 286 shoulders. In this series 2 or more X-rays per shoulder were taken of 89 patients (29 male, 60 female). The various changes in the glenohumeral and acromioclavicular joints were described. Gross destruction appears to be rare, compared to the more frequently seen minor cystic changes. The progress of the disease is often slow or halting. One or both of the shoulders in some of the patients (15 male and 29 female) did not have any detectable X-rays changes, although some of them were followed up for more than 20 years. During our follow-up it became apparent that the acromioclavicular and glenohumeral joints do not follow the same course neither in time nor in severity of joint destruction. Therefore, we divided the shoulder joint into the acromioclavicular and glenohumeral joint. One normal stage and 5 stages of pathology are recognised to fit into previously published schemes of the other joints. Stage 5 appears to be a new phenomenon of neojoint formation, under the previous humeral head with the inferior glenoid rim. Joint disease in the acromioclavicular joint could be divided only into 3 stages.

  4. [Personalized Medicine in Rheumatoid Arthritis].

    Science.gov (United States)

    Kumagai, Shunichi

    2015-10-01

    Medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introductions of biologics and methotrexate as an anchor drug have made it possible to not only suppress pain and inflammation (clinical remission), but also to inhibit joint destruction (structural remission), leading to cure of the disease. In order to achieve this target, it is the most important to diagnose RA early and promote disease remission. However, since the condition and pathology are diverse among patients, optimal treatment for each patient is desired (personalized medicine). Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics (genetic polymorphism, etc.), are indispensable for personalized medicine. We have established a predictive model for methotrexate hepatotoxicity, consisting of 13 SNPs with a sensitivity of 100% and specificity of 89%, although the model should be validated with a larger-scale prospective study. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of anti-CCP antibodies (ACPA); thereafter, secondary stimuli of joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. Cure can be achieved through complete remission by early aggressive treatment and returning to the pre-clinical state of RA with environmental improvement.

  5. Rheumatoid arthritis: Disease or syndrome?

    Science.gov (United States)

    Stanich, Jessica A; Carter, John D; Whittum-Hudson, Judith; Hudson, Alan P

    2009-01-01

    Rheumatoid arthritis (RA) has been described in the medical literature for over two hundred years, but its etiology remains unknown. RA displays phenotypic heterogeneity, and it is a relatively prevalent clinical entity: it affects approximately 1% of the population, resulting in enormous pathologic sequelae. Earlier studies targeting the cause(s) of RA suggested potential infectious involvement, whereas more recent reports have focused on a genetic origin of the disease. However, neither infection nor genetics, nor any other single factor is currently accepted as causative of RA. In this article we review studies relating to the etiology of RA, and those of several related matters, and we conclude that the literature indeed does provide insight into the causes underlying the initiation of RA pathogenesis. Briefly, given the remarkable phenotypic variation of RA, especially in its early stages, as well as a number of other characteristics of the condition, we contend that RA is not a discrete clinical entity with a single etiological source. Rather, we argue that it represents a common clinical endpoint for various starting points, each of which is largely guided by as yet poorly understood aspects of the genetic background of the affected individual. Adoption of this alternative view of the origin of RA will have significant consequences for future research and for development of new therapeutic interventions for this burdensome condition.

  6. 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.

  7. PULMONARY INVOLVEMENT IN RHEUMATOID ARTHRITIS

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    D. V. Bestaev

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is an autoimmune disease with erosive and destructive polyarthritis and systemic manifestations. Pulmonary involvement (PI is common in RA. With high-resolution computed tomography, the detection rate of PI in RA is as high as 50%. PI is a direct cause of death in 10–20% of patients with RA. Autoimmune mechanisms play a leading part in the development of PI in RA. Under the hypothesis advanced by M. Selman et al., that impaired alveolocyte regeneration processes after injury rather inflammation underlie the pathogenesis of pulmonary fibrosis. The pathological process is triggered by damaged alveolocytes and characterized by the migration and proliferation of fibroblasts and myofibroblasts, the suppressed apoptosis of the latter, and the enhanced activity of pneumofibrosis-stimulating cytokines. This gives rise to remodeling of the extracellular matrix, including destruction of the basement membrane, angiogenesis, and fibrosis. The paper considers the types of lung injury in RA and main methods for diagnosis and therapy.

  8. Pain syndrome in rheumatoid arthritis

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    Ekaterina Sergeyevna Filatova

    2011-01-01

    Full Text Available Subjects and methods. One hundred and eighty-three patients with valid rheumatoid arthritis (RA were examined to study the specific fea tures of chronic pain syndrome. The DN4 neuropathic pain diagnostic questionnaire was used to divide all the patients into 2 groups: 1 78 patients with the neuropathic component of pain (NCP and 2 105 patients without the latter. Results. A clinical neurological examination could reveal peripheral nervous system lesion in 96% of Group 1 patients and in 4% of Group 2 ones. The patients with NCP were ascertained to be older, they were longer ill with RA, had higher clinical, X-ray stages and functional class, as well as higher pain intensity. However, no differences were found between the two groups in the values of disease activity (DAS 28 and erythrocyte sedimentation rate. There was a high rate (71% of depressive disorders, the prevalence and degree of which in RA patients were determined by the characteristics of disease severity and did not depend on the presence of NCP. Discussion. The performed study demonstrated that, along with an obligate nociceptive mechanism, the patients with RA had neurogenic and psychogenic components of pain in 43 and 71% of cases, respectively. Consequently, chronic pain syndrome in RA is commonly mixed and both the activity of the inflammatory process and the magnitude of neurogenic and psychogenic components should be borne in mind for optimal pain control.

  9. Biologic interventions for fatigue in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Almeida, Celia; Choy, Ernest H S; Hewlett, Sarah

    2016-01-01

    BACKGROUND: Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage. OBJECTIVES......: To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis. SEARCH METHODS: We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials...... and contacted key authors. SELECTION CRITERIA: We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure. DATA COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed methodological...

  10. The association between rheumatoid arthritis and periodontitis.

    Science.gov (United States)

    Leech, Michelle T; Bartold, P M

    2015-04-01

    The relationship between rheumatoid arthritis and poor oral health has been recognised for many decades. The association between periodontal infection and the risk of developing RA has been the subject of epidemiological, clinical and basic science research in recent times. Converging and reproducible evidence now makes a clear case for the role of specific periodontal infective pathogens in initiating, amplifying and perpetuating rheumatoid arthritis. The unique enzymatic properties of the periodontal pathogen Porphyromonas gingivalis and its contribution to the burden of citrullinated peptides is now well established. The impact of localized infection such as periodontitis in shaping specific anti-citrullinated peptide immune responses highlights a key area for treatment, prevention and risk assessment in rheumatoid arthritis.

  11. Anterior uveitis in juvenile rheumatoid arthritis.

    Science.gov (United States)

    Kanski, J J

    1977-10-01

    The ocular and systemic characteristics of 160 patients with anterior uveitis and seronegative juvenile rheumatoid arthritis are reviewed. Chronic uveitis occurred in 131 patients, 76% of whom were girls. Both eyes were involved in 70% of the cases. Band keratopathy occurred in 41% of the eyes, cataract in 42%, and secondary glaucoma in 19%. Only 11 patients had uveitis before the onset of arthritis. Notable correlations included a pauciarticular onset of arthritis in 95% of the patients, and positive tests for antinuclear antibody in 82%. Of 29 patients with acute anterior uveitis, 27 were boys. The inflammation responded well to therapy, and serious complications did not occur. At follow-up 21 patients had typical ankylosing spondylitis, and five had sacroiliitis. The incidence of positive results of tests for HLA-B27 antigen was 94%.

  12. Screening for uveitis in juvenile chronic arthritis.

    Science.gov (United States)

    Kanski, J J

    1989-03-01

    Three hundred and fifteen patients with anterior uveitis associated with juvenile chronic arthritis (JCA) were studied in order to identify the various risk factors for uveitis. Girls were more susceptible to uveitis than boys by a ratio of 3:1. In 94% of cases the uveitis was diagnosed after the development of arthritis. The risk of uveitis was small after seven or more years had elapsed from the onset of arthritis. Patients with pauciarticular onset JCA had the highest risk of uveitis and systemic onset patients the least risk. The presence of circulating antinuclear antibody was also an important marker for an increased risk of uveitis. A regimen for routine screening of patients is suggested.

  13. Gouty arthritis in the human aging process

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    Juliana Secchi Batista

    2012-09-01

    Full Text Available The aging process has gained universal recognition and is occurring at an accelerated pace. Gout is a metabolic disorder in which an overproduction and / or decreased excretion of uric acid, leading to the deposition of crystals of sodium monourato joints and soft tissue. The present study was based on a literature review that aimed to analyze the incidence of gouty arthritis in the human aging process. To this end, we searched for articles indexed journals, books, among others, published in English and Portuguese, using the keywords "Human Aging", "Rheumatic Diseases", "Drop" and "Gouty Arthritis". The data obtained suggest that the prevalence of gout is higher in men, affecting oligo / polyarticular inflammatory symptoms with smaller and often with involvement of small joints of the hands also may be the coexistence of gout with other autoimmune diseases such as ankylosing spondylitis and rheumatoid arthritis, should be performed nutritional treatment and medication.

  14. Imaging reactive oxygen species in arthritis.

    Science.gov (United States)

    Chen, Wei-Tsung; Tung, Ching-Hsuan; Weissleder, Ralph

    2004-07-01

    Reactive oxygen species (ROS) have been shown to play a role in the pathogenesis of arthritides. Luminol was used as the primary reporter of ROS and photons resulting from the chemiluminescence reaction were detected using a super-cooled CCD photon counting system. Luminol was injected intravenously into groups of animals with different models of arthritis. Imaging signal correlated well with the severity of arthritis in focal and pan-arthritis as determined by histological measurement of ROS by formazan. Measurements were highly reproducible, sensitive, and repeatable. In vivo chemiluminescence imaging is expected to become a useful modality to elucidate the role of ROS in the pathogenesis of arthritides and in determining therapeutic efficacy of protective therapies.

  15. Imaging Reactive Oxygen Species in Arthritis

    Directory of Open Access Journals (Sweden)

    Wei-Tsung Chen

    2004-07-01

    Full Text Available Reactive oxygen species (ROS have been shown to play a role in the pathogenesis of arthritides. Luminol was used as the primary reporter of ROS and photons resulting from the chemiluminescence reaction were detected using a super-cooled CCD photon counting system. Luminol was injected intravenously into groups of animals with different models of arthritis. Imaging signal correlated well with the severity of arthritis in focal and pan-arthritis as determined by histological measurement of ROS by formazan. Measurements were highly reproducible, sensitive, and repeatable. In vivo chemiluminescence imaging is expected to become a useful modality to elucidate the role of ROS in the pathogenesis of arthritides and in determining therapeutic efficacy of protective therapies.

  16. Outcome of ankle arthrodesis in posttraumatic arthritis

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    B S Narayana Gowda

    2012-01-01

    Full Text Available Background: Ankle arthrodesis is still a gold standard salvage procedure for the management of ankle arthritis. There are several functional and mechanical benefits of ankle arthrodesis, which make it a viable surgical procedure in the management of ankle arthritis. The functional outcomes following ankle arthrodesis are not very well known. The purpose of this study was to perform a clinical and radiographic evaluation of ankle arthrodesis in posttraumatic arthritis performed using Charnley′s compression device. Materials and Methods: Between January 2006 and December 2009 a functional assessment of 15 patients (10 males and 5 females who had undergone ankle arthrodesis for posttraumatic arthritis and/or avascular necrosis (AVN talus (n=6, malunited bimalleolar fracture (n=4, distal tibial plafond fractures (n=3, medial malleoli nonunion (n=2. All the patients were assessed clinically and radiologically after an average followup of 2 years 8 months (range 1-5.7 years. Results: All patients had sound ankylosis and no complications related to the surgery. Scoring the patients with the American Orthopaedic Foot and Ankle Society (AOFAS Ankle-Hindfoot scale, we found that 11 of the 15 had excellent results, two had good, and two showed fair results. They were all returned to their preinjury activities. Conclusion: We conclude that, the ankle arthrodesis can still be considered as a standard procedure in ankle arthritis. On the basis of these results, patients should be counseled that an ankle fusion will help to relieve pain and to improve overall function. Still, one should keep in mind that it is a salvage procedure that will cause persistent alterations in gait with a potential for deterioration due to the development of subtalar arthritis.

  17. Colchicine-responsive protracted gouty arthritis with systemic inflammatory reactions.

    Science.gov (United States)

    Nonaka, Fumiaki; Migita, Kiyoshi; Haramura, Tomoko; Sumiyoshi, Remi; Kawakami, Atsushi; Eguchi, Katsumi

    2014-05-01

    Acute gouty arthritis is a severe but self-limiting arthritis caused by inflammatory responses to urate crystals. Oral colchicines are effective for initial stages or prophylaxis, but generally, colchicines are ineffective for established gouty arthritis. We describe an unusual case of gouty arthritis with systemic inflammatory reactions, including high fever and polymyalgia. Refractory polyarthritis and high fever were eradicated by colchicine treatment. Genetic analysis revealed a heterozygous mutation in exon 2 of the MEFV gene (E148Q). This case underscores the possibility that MEFV gene mutations may modify the phenotype of gouty arthritis.

  18. CONVENTIONAL THERAPY OF PSORIATIC ARTHRITIS: EVIDENCE-BASED REVIEW

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    E.R. Soriano

    2011-09-01

    Full Text Available Psoriatic arthritis is a heterogeneous condition, the pattern of which is determined by any combination of pathology affecting peripheral joints, the enthesis and the spine. There is a paucity of evidence for most of the conventional agents used to treat psoriatic arthritis, with many of them being used on the basis of experience in rheumatoid arthritis. Herein, we summarise the evidence compiled relating to effectiveness of treatment for various manifestation of PsA. For those patients with progressive forms of arthritis who may benefit from intervention of newer biological therapies, the continued use of conventional therapy needs ever increasing scrutiny. Key words: Psoriatic arthritis, psoriasis, therapy

  19. Adherence to methotrexate in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bliddal, Henning; Eriksen, Stine A; Christensen, Robin

    2015-01-01

    Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis/contact, with ......Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis...

  20. Cardiovascular disease in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Naranjo, Antonio; Sokka, Tuulikki; Descalzo, Miguel

    2008-01-01

    ABSTRACT: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross......-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire...