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Sample records for arthritis synovial fluid

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

    PubMed

    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. PMID:26270538

  2. Juvenile idiopathic arthritis and rheumatoid arthritis: bacterial diversity in temporomandibular joint synovial fluid in comparison with immunological and clinical findings.

    PubMed

    Olsen-Bergem, H; Kristoffersen, A K; Bjørnland, T; Reseland, J E; Aas, J A

    2016-03-01

    Temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) occurs in up to 80% of affected children. The purpose of this study was to investigate the presence of bacterial DNA in synovial fluid, and to compare this with clinical and immunological findings in children with JIA, adults with persistent JIA, and adults with rheumatoid arthritis, in order to detect whether bacteria contribute to inflammation in TMJ arthritis. Synovial fluid and skin swab samples were collected from 30 patients (54 TMJs). Bacterial detection was performed using 16S rRNA pyrosequencing. Bacterial DNA was detected in 31 TMJs (57%) in 19 patients (63%). A positive statistically significant correlation was registered between bacterial DNA detected in TMJ synovial fluid and the following factors: total protein concentration in synovial fluid, interleukin 1β, tumour necrosis factor alpha, adrenocorticotropic hormone, and adiponectin, as well as the duration of the general medical disease. Fourteen different bacterial species were detected in synovial fluid. Bacterial DNA in TMJ synovial fluid without contamination was detected in more than 50% of the patients. Studies are needed to evaluate the consequences of this bacterial DNA in synovial fluid with regard to TMJ arthritis. PMID:26554824

  3. Candida arthritis: cellular immune responses of synovial fluid and peripheral blood lymphocytes to Candida albicans.

    PubMed Central

    Hermann, E; Mayet, W J; Klein, O; Lohse, A W; Trautwein, C; Michiels, I; Poralla, T; Meyer zum Büschenfelde, K H

    1991-01-01

    A case of septic Candida albicans arthritis of the knee in a patient with systemic candidiasis is presented. Systemic and intra-articular cellular immune responses to C albicans and various bacterial antigens were monitored for 15 weeks. It is shown that the candida induced blastogenesis of synovial fluid lymphocytes was much more stimulated than that of peripheral blood lymphocytes, and that the proportion of activated cells expressing HLA class II antigens was markedly increased in the synovial fluid. Strong cellular immune responses to Candida albicans could still be shown many weeks after the synovial fluid aspirates had become sterile. For the first time synovial fluid derived, CD4 positive T lymphocyte clones with specificity for candida antigens were characterised and further propagated in vitro. Images PMID:1720301

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

    SciTech Connect

    Duby, A.D.; Sinclair, A.K.; Osborne-Lawrence, S.L. ); Zeldes, W.; Kan, Li; Fox, D.A. )

    1989-08-01

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

  5. [Diagnosis: synovial fluid analysis].

    PubMed

    Gallo Vallejo, Francisco Javier; Giner Ruiz, Vicente

    2014-01-01

    Synovial fluid analysis in rheumatological diseases allows a more accurate diagnosis in some entities, mainly infectious and microcrystalline arthritis. Examination of synovial fluid in patients with osteoarthritis is useful if a differential diagnosis will be performed with other processes and to distinguish between inflammatory and non-inflammatory forms. Joint aspiration is a diagnostic and sometimes therapeutic procedure that is available to primary care physicians. PMID:24467958

  6. Urokinase, a constitutive component of the inflamed synovial fluid, induces arthritis

    PubMed Central

    Jin, Tao; Tarkowski, Andrej; Carmeliet, Peter; Bokarewa, Maria

    2003-01-01

    Urokinase plasminogen activator (uPA) is an important regulator of fibrinolysis in synovial fluid. An increase of uPA activity and expression of its receptor have been reported in joints of patients with rheumatoid arthritis (RA). The aim of the present study was to assess the arthritogenic capacity of uPA and the mechanisms by which this effect is mediated. uPA was injected into the knee joints of healthy mice, and morphological signs of arthritis were assessed 4 days after the injection. The prerequisite of different leukocyte populations for the development of uPA-triggered arthritis was assessed by selective cell depletion. The inflammatory capacity of uPA was assessed in vitro. Finally, levels of uPA were measured in 67 paired blood and synovial fluid samples from RA patients. The synovial fluid from RA patients displayed higher levels of uPA compared with blood samples. Morphological signs of arthritis were found in 72% of uPA-injected joints compared with in only 18% of joints injected with PBS (P < 0.05). Synovitis was characterised by infiltration of CD4-Mac-1+ mononuclear cells, by the formation of pannus and by occasional cartilage destruction. The absence of monocytes and lymphocytes diminished the frequency of synovitis (P < 0.01), indicating an arthritogenic role of both these leukocyte populations. Synthetic uPA inhibitor downregulated the incidence of uPA-triggered arthritis by 50%. uPA induced arthritis, stimulating the release of proinflammatory cytokines IL-6, IL-1β and tumour necrosis factor alpha. Accumulation of uPA locally in the joint cavity is a typical finding in erosive RA. uPA exerts potent arthritogenic properties and thus may be viewed as one of the essential mediators of joint inflammation. PMID:12716448

  7. Interleukin 35 Synovial Fluid Levels Are Associated with Disease Activity of Rheumatoid Arthritis

    PubMed Central

    Šenolt, Ladislav; Šumová, Barbora; Jandová, Romana; Hulejová, Hana; Mann, Heřman; Pavelka, Karel; Vencovský, Jiří; Filková, Mária

    2015-01-01

    Objectives To study the association of systemic and local interleukin-35 (IL-35) levels in rheumatoid arthritis. Methods 37 patients with treatment naïve early RA, 49 with established RA and 29 control patients with osteoarthritis (OA) were studied. Serum and paired synovial fluid samples were analysed for IL-35. Disease activity of RA patients was assessed according to the 28-Joint Count Disease Activity Score (DAS28). Results The levels of serum IL-35 were significantly higher in patients with treatment naïve early RA compared to those with established disease and control OA subjects. In addition, serum levels of IL-35 significantly decreased 12 weeks after initiation of glucocorticoids and conventional synthetic disease modifying antirheumatic drugs in patients with treatment naïve early RA. Synovial fluid IL-35 levels were significantly higher in RA compared to OA patients, were significantly elevated compared to serum counterparts and correlated with synovial fluid leukocyte count (r=0.412; p<0.01), serum CRP levels (r=0.362; p<0.05) and DAS28 (r=0.430, p<0.01). Conclusion This is the first study showing elevated circulating levels of IL-35 in treatment naïve early RA, its significant decrease after treatment initiation and positive association between increased synovial fluid IL-35 and disease activity in patients with long-lasting RA. PMID:26204444

  8. Concentrations of glycosaminoglycans in synovial fluids and their relation with immunological and inflammatory mediators in rheumatoid arthritis.

    PubMed Central

    Bensouyad, A; Hollander, A P; Dularay, B; Bedwell, A E; Cooper, R A; Hutton, C W; Dieppe, P A; Elson, C J

    1990-01-01

    The dimethylmethylene blue assay showed higher concentrations of glycosaminoglycans in many synovial fluids from patients with rheumatoid arthritis (RA) than in autologous sera or sera or synovial fluids from normal subjects. These results were taken to suggest that the glycosaminoglycans in RA synovial fluid were abnormally raised and derived from cartilage. To discover what stimulated such glycosaminoglycan release in RA joints relations were sought between synovial fluid concentrations of glycosaminoglycans and immunological and inflammatory mediators. It was shown that RA synovial fluid glycosaminoglycan concentrations correlated with synovial fluid C3d concentrations but not with synovial fluid rheumatoid factor concentrations, polymorphonuclear leucocyte numbers, myeloperoxidase concentrations, or the ability of the synovial fluids to release free radicals from normal polymorphonuclear leucocytes. A correlation was found between synovial fluid C3d and interleukin 1 concentrations as judged by both lymphocyte activating factor activity and immunoassay, but no significant correlation was detected between interleukin 1 and glycosaminoglycan concentrations. It is suggested that in the rheumatoid joint locally produced cytokines, in addition to interleukin 1, together stimulate glycosaminoglycan release from cartilage and render it vulnerable to attack by other processes. PMID:2344209

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

    PubMed Central

    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. PMID:26270538

  10. Identification of oral bacterial DNA in synovial fluid of arthritis patients with native and failed prosthetic joints

    PubMed Central

    Témoin, Stéphanie; Chakaki, Alia; Askari, Ali; El-Halaby, Ahmed; Fitzgerald, Steven; Marcus, Randall E.; Han, Yiping W.; Bissada, Nabil F.

    2013-01-01

    Objective We examined the presence of bacterial DNA in synovial fluids of native or aseptically failed prosthetic joints from patients having periodontal disease and arthritis to determine if there is bacterial spread from the oral cavity to the joints. Methods A total of 36 subjects were enrolled in the study. Among these, 11 were diagnosed with rheumatoid arthritis (RA), and 25 with osteoarthritis (OA). Eight patients with OA and are with RA had failed prostheses. Synovial fluid was aspirated from the affected hip or knee joint. Pooled subgingival plaque samples were collected followed by clinical periodontal examination. Bacterial DNA was extracted from the collected synovial fluid and dental plaque samples followed by polymerase chain reactions (PCR) and DNA sequence analysis of the 16S-23S rRNA genes. Results Of the 36 subjects, bacterial DNA was detected in the synovial fluid samples from five patients (13.9%), two with rheumatoid arthritis (one native and one failed prosthetic joints) and three with osteoarthritis (one native and two failed prosthetic joints). Of these five patients, two were diagnosed with periodontitis and had identical bacterial clones (Fusobacterium nucleatum and Serratia proteamaculans, respectively) detected in both the synovial fluid and dental plaque samples. Conclusions The present findings of this bacterial DNA in synovial fluid suggest the possibility of infection translocating from the periodontal tissue to the synovium. We suggest that patients with arthritis or failed prosthetic joints be examined for the presence of periodontal diseases and that be treated accordingly. PMID:22426587

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

    PubMed Central

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

    2016-01-01

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

  12. Synovial fluid analysis

    MedlinePlus

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

  13. The influence of corticosteroids on sequential clinical and synovial fluid parameters in joints with acute infectious arthritis in the horse.

    PubMed

    Tulamo, R M; Bramlage, L R; Gabel, A A

    1989-09-01

    Infectious arthritis was induced experimentally in one tarsocrural joint of six horses by intra-articular injection of 1 ml Staphylococcus aureus-saline suspension with the addition of 200 mg methylprednisolone acetate. The corresponding contralateral joint was injected with 1 ml of saline with the addition of 200 mg methylprednisolone acetate, and served as a control. The purpose of the experiment was to examine the effect of corticosteroids on the acute clinical signs of infectious arthritis, and the associated changes in synovial fluid, to separate the effects of a steroid injection from those of infection alone. This should aid early diagnosis of infection. The progression of the infectious arthritis was assessed over nine days by clinical examination and sequential synovial fluid analysis. The corticosteroids masked the clinical signs in some horses for up to the third day although changes in the synovial fluid were present earlier. Cellular changes preceded biochemical changes initially. Leucocyte counts showed a significant increase in cell numbers after infection was established. Persistent neutrophilia, over 90 per cent, together with a pH under 6.9 were the most consistent findings in the infected synovia. Total protein values were lower in infected joints with, than those without, corticosteroids; although there was a progressive rise in total protein concentration throughout the experiment in both groups. Serum and synovial glucose difference and synovial lactate had very little diagnostic value because significant increases due to the corticosteroids were documented in the control joints. PMID:2776719

  14. Detection of Epstein-Barr virus in synovial fluid of rheumatoid arthritis patients

    PubMed Central

    Mahabadi, Mostafa; Faghihiloo, Ebrahim; Alishiri, Gholam Hossein; Ataee, Mohamad Hossein; Ataee, Ramezan Ali

    2016-01-01

    Introduction Rheumatoid arthritis (RA) is one of the most common chronic inflammatory disorders. Genes and environmental factors contribute to RA. Epstein–Barr Virus (EBV) has been considered as one the RA pathogeneses. The aim of this study was to detect of the EBV genome in patients with RA. Methods In this cross-sectional study, 50 samples of synovial fluid were obtained from patients with RA from 2010–2012. Using a standard of the EBV genome and EBNA-1-specific primers, the method of PCR was set up. Then, all of the samples of synovial fluids separately were subjected to DNA extraction and Polymerase Chain Reaction (PCR) amplification. Data were analyzed using SPSS version 18.0. The statistical analysis was performed by the t-test. Results The demographic and laboratory characteristic assay revealed that the mean age of patients was 49, and the patients were 60% males and 40% females. In addition, in all cases, the mean rheumatoid factor (RF) levels of the patients were below the normal level. The results of this study showed that the PCR was able to detect EBV DNA in > 60% of the cases. Conclusion The results of this study indicated that EBV was frequently detected in the synovial fluid of RA patients. Thus, EBV may be a strong candidate that can act at several levels of the pathophysiology of RA. However, these findings also indicated that EBV may play a role in the pathogenesis of RA. However, the possible relationship between RA and EBV must be determined by further research. PMID:27123228

  15. Elevated soluble CD8 in the synovial fluid from patients with rheumatoid arthritis.

    PubMed

    Carpenter, A B; Eisenbeis, C H; Carrabis, S; Brown, M C; Ip, S H

    1990-01-01

    Suppressor/cytotoxic T cells express the surface marker CD8, which can be measured in a soluble form in culture supernatants of activated human lymphocytes. Using a sandwich immunoassay, we assessed the levels of soluble CD8 (sCD8) in serum from patients with rheumatoid arthritis (RA; n = 82), patients with degenerative joint disease (DJD; n = 40), and healthy controls. There were no differences in serum sCD8 levels among these groups. In contrast, the levels of soluble CD8 in the synovial fluid (SF) from patients with RA (n = 53) were significantly increased compared with the levels in 23 samples from patients with DJD (821 +/- 110 U/ml versus 213 +/- 13 U/ml, p less than 0.001). Synovial fluid sCD8 levels in the RA group were strikingly elevated, to a maximum value of 5,026 U/ml. In the majority of RA SF specimens (39 of 53), the values were significantly higher in the SF than the serum. Although the RA group had higher values of sCD8, such values were not significantly correlated with measured laboratory or clinical parameters. Current clinical and laboratory methods of evaluating patients may not be adequate in dealing with the complexity and heterogeneity of RA. Soluble CD8 values may be useful in further grouping patients with this disease. PMID:2121924

  16. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis

    PubMed Central

    Kotake, Shigeru; Udagawa, Nobuyuki; Takahashi, Naoyuki; Matsuzaki, Kenichiro; Itoh, Kanami; Ishiyama, Shigeru; Saito, Seiji; Inoue, Kazuhiko; Kamatani, Naoyuki; Gillespie, Matthew T.; Martin, T. John; Suda, Tatsuo

    1999-01-01

    IL-17 is a newly discovered T cell–derived cytokine whose role in osteoclast development has not been fully elucidated. Treatment of cocultures of mouse hemopoietic cells and primary osteoblasts with recombinant human IL-17 induced the formation of multinucleated cells, which satisfied major criteria of osteoclasts, including tartrate-resistant acid phosphatase activity, calcitonin receptors, and pit formation on dentine slices. Direct interaction between osteoclast progenitors and osteoblasts was required for IL-17–induced osteoclastogenesis, which was completely inhibited by adding indomethacin or NS398, a selective inhibitor of cyclooxgenase-2 (COX-2). Adding IL-17 increased prostaglandin E2 (PGE2) synthesis in cocultures of bone marrow cells and osteoblasts and in single cultures of osteoblasts, but not in single cultures of bone marrow cells. In addition, IL-17 dose-dependently induced expression of osteoclast differentiation factor (ODF) mRNA in osteoblasts. ODF is a membrane-associated protein that transduces an essential signal(s) to osteoclast progenitors for differentiation into osteoclasts. Osteoclastogenesis inhibitory factor (OCIF), a decoy receptor of ODF, completely inhibited IL-17–induced osteoclast differentiation in the cocultures. Levels of IL-17 in synovial fluids were significantly higher in rheumatoid arthritis (RA) patients than osteoarthritis (OA) patients. Anti–IL-17 antibody significantly inhibited osteoclast formation induced by culture media of RA synovial tissues. These findings suggest that IL-17 first acts on osteoblasts, which stimulates both COX-2–dependent PGE2 synthesis and ODF gene expression, which in turn induce differentiation of osteoclast progenitors into mature osteoclasts, and that IL-17 is a crucial cytokine for osteoclastic bone resorption in RA patients. PMID:10225978

  17. Evidence for locally synthesized and clonally restricted immunoglobulin in the synovial fluid from rheumatoid arthritis patients.

    PubMed

    Carpenter, A B; Huczko, E; Eisenbeis, C H; Kelly, R H

    1990-12-13

    In this study, we examined the immunoglobulin (Ig) present in synovial fluid (SF) from patients with rheumatoid arthritis (RA) to determine if it was locally produced and to assess the presence of clonally restricted (oligoclonal) immunoglobulin. We studied SF/serum pairs from 55 RA patients and 23 patients with degenerative joint disease (DJD). We found increases in total protein, IgG, IgA, and IgM in RA vs DJD SF (P less than 0.01). The immunoglobulin present in RA appeared to be locally produced as evidenced by significant increases (P less than 0.01) in the immunoglobulin indices. Regression analysis among the levels of IgG, IgA, and IgM RF and the Ig indices suggested that only a minority of the locally synthesized Ig present was specific for RF. To provide evidence of clonal restriction, we further analyzed the SF specimens by isoelectric focusing and assessed the presence of oligoclonal bands present only in RA SF. In 7/55 RA specimens (13%) we found unique SF IgG bands. All bands were of similar isoelectric point (pI), being quite cathodic with pI greater than 7.5. Our evidence supports synthesis of Ig within RA synovium, with a minority of patients showing prominent and unique SF Ig bands. This suggests an oligoclonal response in SF of some patients, but polyclonal Ig synthesis in most. PMID:2073742

  18. Soluble interleukin-2 receptor: elevated levels in serum and synovial fluid of patients with rheumatoid arthritis.

    PubMed

    Carpenter, A B; Eisenbeis, C H; Carrabis, S; Brown, M C; Ip, S H

    1990-01-01

    Soluble interleukin-2 receptor (sIL-2R) levels were quantitated in the serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and degenerative joint disease (DJD). A sandwich immunoassay, employing two monoclonal antibodies against distinct epitopes on the IL-2R, was utilized for measurement. We found a striking elevation of sIL-2R in RA SF as compared with DJD SF (RA, 1319 +/- 135; DJD, 416 +/- 59; p less than 0.001). RA serum sIL-2R levels were also significantly elevated over DJD levels. There was no interaction between rheumatoid factor (RF) and sIL-2R. RA patients with elevated sIL-2R levels had significantly longer disease duration, higher c-reactive protein (CRP) levels in serum and SF, and higher RF levels in serum and SF. The groups were similar in regard to other laboratory variables. The presence of elevated levels of sIL-2R in RA serum and SF confirms the presence of a heightened immune reactivity and in vivo activation of lymphocytes in RA. PMID:2313471

  19. Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood.

    PubMed Central

    Combe, B; Pope, R M; Fischbach, M; Darnell, B; Baron, S; Talal, N

    1985-01-01

    Several aspects of interleukin-2 (IL-2) generation and function were studied employing mononuclear cells from synovial fluid (SF), synovial tissue (ST) and peripheral blood (PB) of patients with rheumatoid arthritis (RA). Decreased PHA stimulated IL-2 production by lymphocytes from rheumatoid ST, SF (P less than 0.02), and PB (P less than 0.01) was observed when compared to normal blood and SF of patients with gout. The proliferative response of rheumatoid lymphocyte blasts exposed to exogenous IL-2 was also defective (P less than 0.05-0.001). This defect was greater in SF than in rheumatoid PB (P less than 0.05-0.001). In addition to the proliferative response, the effect of IL-2 on interferon-gamma (IFN-gamma) production was also examined. Rheumatoid lymphocytes from both PB and SF produced less IFN-gamma after overnight treatment with IL-2 than did normal PB lymphocytes. This decreased IFN-gamma induction was discordant with the excellent enhancement by IL-2 of natural killer activity. Removal of adherent cells in synovial fluid did not correct this deficit. Abnormalities in the biology of IL-2 and IFN-gamma suggest that impaired T cell function could contribute to the immunopathogenesis of RA. PMID:3921298

  20. Presence of Cyclophilin A in Synovial Fluids of Patients with Rheumatoid Arthritis

    PubMed Central

    Billich, Andreas; Winkler, Gottfried; Aschauer, Heinrich; Rot, Antal; Peichl, Peter

    1997-01-01

    Cyclophilins have been suggested to act as leukocyte chemotactic factors produced in the course of inflammation. Therefore we looked for the presence of cyclophilins in the synovial fluids (SF) from patients with rheumatoid arthritis (RA). Peptidyl prolyl cis–trans isomerase activity (PPIase) was measured in SF from knee punctures of 26 patients with RA and five patients with knee osteoarthritis (OA). PPIase was detected in SF from RA patients, but not in samples from OA patients. Enzyme activity was sensitive to inhibition by cyclosporin A (IC50 = 28–50 nM). Estimated concentrations of the SF-derived cyclophilin based on the enzyme activity were in the range of 11 to 705 nM. The presence of cyclophilin in the SF showed disease correlation; its concentration correlated with the number of cells in the SF (r   = 0.91, P <0.0001) and with the percentage of neutrophils in the cellular infiltrate and was higher in more acute cases of joint swelling. In immunoblots of partially purified preparations of SF from RA patients, an ∼18-kD protein band reacted with polyclonal antibodies that recognize cyclophilin A and B, but not with antibodies specific for cyclophilin B. Sequencing of this protein revealed identity of the NH2-terminal amino acids with those of human cyclophilin A. The finding is unexpected since cyclophilin B rather than A is generally regarded as the secreted isoform, the presence of cyclophilin A being confined to the cytoplasm. Our data support the hypothesis that cyclophilins may contribute to the pathogenesis of inflammatory diseases, possibly by acting as cytokines. This may offer a possible explanation of the effectiveness of cyclosporin A in RA, in addition to the known immunosuppressive effects of the drug. PMID:9120404

  1. Evidence for enhanced interleukin 2 (IL-2) secretion and IL-2 receptor presentation by synovial fluid lymphocytes in rheumatoid arthritis.

    PubMed Central

    Lemm, G; Warnatz, H

    1986-01-01

    Synovial fluid lymphocytes (SFL) and peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA) and reactive oligoarthritis were investigated for activated T cells (Ia+SIg-), IL-2 receptor bearing cells (Tac+) and IL-2 production in vivo and in vitro. In contrast to negative results with blood, the synovial fluid of the arthritic joints contains considerable amounts of IL-2 activity (median: 11.8 mu/ml), elevated proportions of Ia+SIg- activated T cells (median: 12.5%) and of IL-2 receptor bearing cells (median: 2.5%). In vitro, after stimulation with several Concanavalin A (Con A) doses, SFL develop proportions of IL-2 receptor cells comparable to PBL. Furthermore, they produce higher values of IL-2 activity than comparable PBL cultures. The proportions of Ia+SIg- activated T cells increase only moderately after Con A stimulation compared to in vivo data, indicating different activated T cell subsets in the synovial fluid (Ia+SIg-, Tac+). The findings are discussed as an expression of an acute hyperactivation of lymphocytes in an inflamed joint. PMID:3089651

  2. Synovial fluid analysis by ferrography.

    PubMed

    Evans, C H; Bowen, E R; Bowen, J; Tew, W P; Westcott, V C

    1980-01-01

    Ferrography is a technique for magnetically harvesting and separating metallic particles from aqueous and non-aqueous suspensions. We have adapted this method of analysis to the study of cartilaginous and osseous wear particles, as well as fragments of soft tissue, found in the synovial fluid of human joints. As ferrography employes magnetism to harvest particles and arrange them in an orderly fashion, it is first necessary to impart a positive magnetic susceptibility to the biological materials. The trivalent paramagnetic cation of the rare earth element erbium is used for this purpose. Based on this principle, a method for the ferrographic analysis of synovial fluid has been devised, which is presently being employed in the study of human joint disease. Using this technique, improved diagnosis of arthritis may be possible. In addition, it may lead to a deeper understanding of the aetiology and pathogenesis of degenerative arthritis and other destructive joint diseases. PMID:7419857

  3. Characterization of CD30/CD30L+ Cells in Peripheral Blood and Synovial Fluid of Patients with Rheumatoid Arthritis

    PubMed Central

    Dolcino, Marzia; Tinazzi, Elisa; Rigo, Antonella; Argentino, Giuseppe; Patuzzo, Giuseppe; Beri, Ruggero; Puccetti, Antonio

    2015-01-01

    The CD30/CD30L signalling system has been implicated in the pathogenesis of several autoimmune and inflammatory conditions. In rheumatoid arthritis (RA), soluble CD30 (sCD30) levels reflect the recruitment of CD30+ T cells into the inflamed joints and correlate with a positive response to immunosuppressive therapy. The aim of our report was to clarify the role of CD30/CD30L signalling system in the pathogenesis of RA. Our analysis of the CD30L+ T cell subsets in peripheral blood (PB) and synovial fluid (SF) of RA patients and of the related cytokine profiles suggests the involvement of CD30/CD30L signalling in polarization of T cells towards a Th17 phenotype with proinflammatory features. Moreover, in RA SF nearly 50% of Treg cells express CD30, probably as an attempt to downmodulate the ongoing inflammation. We also show here that the engagement of CD30L on neutrophils stimulated with CD30/Fc chimera may play a crucial role in RA inflammation since activated neutrophils release IL-8, thus potentially amplifying the local inflammatory damage. In conclusion, the results obtained suggest that the complex CD30/CD30L signalling pathway is implicated in the pathogenesis and progression of RA synovitis through a concerted action on several immune effector cells. PMID:26090498

  4. Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid arthritis using LC-MALDI-TOF/TOF.

    PubMed

    Wang, Fei; Chen, Fang-Fang; Gao, Wen-Bo; Wang, Hai-Yong; Zhao, Ning-Wei; Xu, Min; Gao, De-Yu; Yu, Wei; Yan, Xiao-Ling; Zhao, Jian-Ning; Li, Xiao-Jun

    2016-09-01

    The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens. A total of 182 citrullinated peptides and 200 citrullinated sites were identified in RA SFs, while 3 citrullinated peptides and 4 citrullinated sites were identified in OA SFs. The 182 citrullinated peptides from RA SFs and the 3 citrullinated peptides from OA SFs were derived from 83 and 3 autoantigens, respectively. Eighty-three autoantigens except protein-arginine deiminase type-2 (PADI2) and protein-arginine deiminase type-2 (PADI4) were over-citrullinated compared with controls, and the citrullinated sites of PADI2 and PADI4 were different in two groups. Interestingly, citrullinated histone H3.3 (H3F3A) was found in OA controls, but not in RA groups. The differential citrullinated proteins identified in RA SFs suggested potential autoantigens were targeted for ACPAs response and might contribute to the induction and perpetuation of complement activation and joint inflammation in RA. PMID:27060082

  5. Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA)

    PubMed Central

    Ribbens, C; Bonnet, V; Kaiser, M J; Andre, B; Kaye, O; Franchimont, N; De Groote, D; Beguin, Y; Malaise, M G

    2000-01-01

    Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1β, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen’s grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0·05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0·65, P = 0·0001) and sCD25 (r = 0·39, P = 0·0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest. PMID:10759783

  6. Plasma and Synovial Fluid TrxR Levels are Correlated With Disease Risk and Severity in Patients With Rheumatoid Arthritis

    PubMed Central

    Xie, Zhijun; Sun, Jing; Li, Haichang; Shao, Tiejuan; Wang, Dawei; Zheng, Qi; Wen, Chengping

    2016-01-01

    Abstract This study was designed and performed to establish the relationship between plasma and synovial fluid (SF) levels of thioredoxin reductase (TrxR) and disease activity in Chinese patients with rheumatoid arthritis (RA). This study consisted of a total of 224 patients diagnosed with RA, 224 age and sex-matched healthy controls, and 156 patient controls. The disease activity of RA patients was calculated as diseases activity score that include 28-joint counts (DAS 28), which was divided into low-diseases activity (LDA) and high-diseases activity (HDA) groups. Increased plasma TrxR was detected in patients with RA than healthy controls (P < 0.0001). With an area under the curve (AUC) of 0.874, plasma TrxR showed a evidently greater discriminatory ability than C-reactive protein (CRP; AUC, 0.815), antistreptolysin-O (ASO; AUC, 0.631), rheumatoid factor (RF, AUC, 0.793), and erythrocyte sedimentation rate (ESR, AUC, 0.789) in diagnosing RA. RA patients with HDA had significantly elevated TrxR levels in plasma and SF than did those with LDA (P < 0.0001). With an AUC of 0.874, plasma TrxR levels as an indicator for screening of HDA showed a significantly greater discriminatory ability than CRP (AUC, 0.690), ASO (AUC, 0.597), RF (AUC, 0.657), and ESR (AUC, 0.603). Similarly, SF TrxR levels as an indicator for screening of HDA also showed a significantly greater discriminatory ability as compared with above biomarkers. TrxR levels in plasma and SF were positively correlated with the severity of RA. TrxR levels may therefore serve as a new biomarker in addition of the traditional biomarkers for assessing the risk and severity of RA. Further analysis of TrxR release machinery may give us a new understanding of pathogenesis of RA. PMID:26871773

  7. Immunoglobulin G and A Antibody Responses to Bacteroides forsythus and Prevotella intermedia in Sera and Synovial Fluids of Arthritis Patients

    PubMed Central

    Moen, Ketil; Brun, Johan G.; Madland, Tor Magne; Tynning, Turid; Jonsson, Roland

    2003-01-01

    The objective of the present study was to investigate immunoglobulin G (IgG) and IgA antibody immune responses to Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, and Candida albicans in the sera of patients with rheumatoid arthritis (RA), the synovial fluid (SF) of patients with RA (RA-SF samples), and the SF of patients without RA (non-RA-SF samples). An enzyme-linked immunosorbent assay was used to determine IgG and IgA antibody levels in 116 serum samples from patients with RA, 52 RA-SF samples, and 43 non-RA-SF samples; and these were compared with those in SF samples from 9 patients with osteoarthritis (OA-SF samples) and the blood from 100 donors (the control [CTR] group). Higher levels of IgG antibodies against B. forsythus (P < 0.0001) and P. intermedia (P < 0.0001) were found in non-RA-SF samples than in OA-SF samples, and higher levels of IgG antibodies against B. forsythus (P = 0.003) and P. intermedia (P = 0.024) were found in RA-SF samples than in OA-SF samples. Significantly higher levels of IgA antibodies against B. forsythus were demonstrated in both RA-SF and non-RA-SF samples than in OA-SF samples. When corrected for total Ig levels, levels of IgG antibody against B. forsythus were elevated in RA-SF and non-RA-SF samples compared to those in OA-SF samples. Lower levels of Ig antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group for both IgG (P = 0.003) and IgA (P < 0.0001). When corrected for total Ig levels, the levels of IgG and IgA antibodies against B. forsythus were still found to be lower in the sera from patients with RA than in the plasma of the CTR group (P < 0.0001). The levels of antibodies against P. gingivalis and C. albicans in the sera and SF of RA and non-RA patients were comparable to those found in the respective controls. The levels of IgG and IgA antibodies against B. forsythus were elevated in SF from patients with RA and non-RA-SF samples

  8. MHC restriction of synovial fluid lymphocyte responses to the triggering organism in reactive arthritis. Absence of a class I-restricted response.

    PubMed Central

    Hassell, A B; Pilling, D; Reynolds, D; Life, P F; Bacon, P A; Gaston, J S

    1992-01-01

    Synovial fluid mononuclear cells (SFMC) from patients with reactive arthritis (ReA) show marked proliferative responses to preparations of the organism triggering the arthritis. Initial studies with MHC-specific MoAbs have indicated that a significant element of these proliferative responses is mediated by class II MHC-restricted CD4+ T cells. It is imperative to establish the presence or absence of a class I-restricted response, for two reasons. Firstly, the association of ReA with the MHC class I molecule, HLA B27, raises the possibility of there being a B27-restricted response to the triggering organism. Secondly, a number of the organisms associated with ReA are intracellular pathogens, whose antigens might be expected to be presented by class I MHC molecules. In an effort to identify a class I MHC-restricted pathogen-specific response in the SFMC of ReA patients, we have assessed the proliferative responses of SFMC depleted of CD4+ T cells. Responses were grossly diminished by CD4+ T cell depletion. We also investigated Chlamydia-specific cytotoxicity in the SFMC of patients with sexually acquired ReA in a system using productive chlamydial infection to produce both targets and effectors. Significant antigen specific cytotoxicity was not seen. These experiments do not provide evidence to support the existence of pathogen-specific responses by CD8+, class I-restricted synovial fluid T cells in ReA. PMID:1606728

  9. Synergistic Effects of Ethanol and Isopentenyl Pyrophosphate on Expansion of γδ T Cells in Synovial Fluid from Patients with Arthritis

    PubMed Central

    Laurent, Agneta J.; Bindslev, Niels; Johansson, Björn; Berg, Louise

    2014-01-01

    Low to moderate ethanol consumption has been associated with protective effects in autoimmune diseases such as rheumatoid arthritis, RA. An expansion of γδ T cells induced by isopentenyl pyrophosphate, IPP, likewise seems to have a protective role in arthritis. The aim of this project was to test the hypothesis that low doses of ethanol can enhance IPP-induced expansion of synovial fluid γδ T cells from patients with arthritis and may thereby potentially account for the beneficial effects of ethanol on symptoms of the arthritic process. Thus, mononuclear cells from synovial fluid (SF) from 15 patients with arthritis and from peripheral blood (PB) from 15 healthy donors were stimulated with low concentrations of ethanol and IPP for 7 days in vitro. IPP in combination with ethanol 0.015%, 2.5 mM, equivalent to the decrease per hour in blood ethanol concentration due to metabolism, gave a significantly higher fractional expansion of SF γδ T cells compared with IPP alone after 7 days (ratio 10.1+/−4.0, p<0.0008, n = 12) in patients with arthritis. Similar results were obtained for PB γδ T cells from healthy controls (ratio 2.0+/−0.4, p<0.011, n = 15). The augmented expansion of γδ T cells in SF is explained by a higher proliferation (p = 0.0034, n = 11) and an increased survival (p<0.005, n = 11) in SF cultures stimulated with IPP plus ethanol compared to IPP alone. The synergistic effects of IPP and ethanol indicate a possible allosteric effect of ethanol. Similar effects could be seen when stimulating PB with ethanol in presence of risedronate, which has the ability to increase endogenous levels of IPP. We conclude that expansion of γδ T cells by combinatorial drug effects, possibly in fixed-dose combination, FDC, of ethanol in the presence of IPP might give a protective role in diseases such as arthritis. PMID:25090614

  10. Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis (RA) is an inflammatory disease, which results in destruction of the joint. The presence of immune complexes (IC) in serum and synovial fluid of RA patients might contribute to this articular damage through different mechanisms, such as complement activation. Therefore, identification of the antigens from these IC is important to gain more insight into the pathogenesis of RA. Since RA patients have antibodies against citrullinated proteins (ACPA) in their serum and synovial fluid (SF) and since elevated levels of citrullinated proteins are detected in the joints of RA patients, citrullinated antigens are possibly present in IC from RA patients. Methods IC from serum of healthy persons, serum of RA patients and IC from synovial fluid of RA patients and Spondyloarthropathy (SpA) patients were isolated by immunoprecipitation. Identification of the antigens was performed by SDS-PAGE, mass spectrometry and immunodetection. The presence of citrullinated proteins was evaluated by anti-modified citrulline (AMC) staining. Results Circulating IC in the serum of RA patients and healthy controls contain fibrinogenβ and fibronectin, both in a non-citrullinated form. Additionally, in IC isolated from RA SF, fibrinogenγ and vimentin were identified as well. More importantly, vimentin and a minor portion of fibrinogenβ were found to be citrullinated in the isolated complexes. Moreover these citrullinated antigens were only found in ACPA+ patients. No citrullinated antigens were found in IC from SF of SpA patients. Conclusions Citrullinated fibrinogenβ and citrullinated vimentin were found in IC from SF of ACPA+ RA patients, while no citrullinated antigens were found in IC from SF of ACPA- RA patients or SpA patients or in IC from serum of RA patients or healthy volunteers. The identification of citrullinated vimentin as a prominent citrullinated antigen in IC from SF of ACPA+ RA patients strengthens the hypothesis that citrullinated vimentin

  11. Distribution of interleukin-10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation

    PubMed Central

    Scrivo, R; Conigliaro, P; Riccieri, V; Di Franco, M; Alessandri, C; Spadaro, A; Perricone, R; Valesini, G

    2015-01-01

    Evidence exists that interleukin (IL)-10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL-20, IL-24 and IL-19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL-20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL-24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL-19 serum levels were higher in HC and OA compared with PsA and RA patients; IL-19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL-19 serum levels after biological treatment. Therefore, IL-19 seems to be involved mainly in the joint inflammation, whereas IL-20 and IL-24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies. PMID:25178435

  12. HTLV-I associated arthritis: characteristics of an HTLV-I virus infected T cell line from synovial fluid.

    PubMed Central

    Eguchi, K; Nakamura, T; Mine, M; Ida, H; Kawakami, A; Migita, K; Nagasato, K; Kurata, A; Fukuda, T; Nagataki, S

    1992-01-01

    A T cell line from mononuclear cells in the synovial fluid of a patient with polyarthritis was established. The T cell line reacted with serum samples positive for antibodies to human T cell lymphotropic virus type I (HTLV-I) and with monoclonal antibody to HTLV-I p19. In Southern blotting with an env-pX-LTR HTLV-I probe and digestion of T cell line DNA with the restriction enzymes ClaI, DraI, and PstI generated fragments that were identical to those found in two HTLV-I infected T cell lines established from adult T cell leukaemia or HTLV-I associated myelopathy. The T cell line expressed CD2, CD3, CD4, CD45RA, CD29, HLA-DR, CD25, and CD26 antigens, but not CD8 and CD20 antigens. Large amounts of interleukin 6, interferon gamma, and tumour necrosis factor alpha were secreted in the culture supernatants of this cell line. This line helped immunoglobulin production by B cells, but not K562, Raji, and synovial cell lysis. Images PMID:1616338

  13. Inhibition of myeloperoxidase by synovial fluid and serum.

    PubMed Central

    Dularay, B; Yea, C M; Elson, C J

    1991-01-01

    An inhibitor of myeloperoxidase has been identified in the synovial fluids and sera from patients with rheumatoid arthritis and sera from normal subjects. Initially, these fluids were found to inhibit stimulus induced degranulation of polymorphonuclear leucocytes independently of the stimulating agent. Subsequently, the fluids were shown to inhibit the released enzyme rather than the degranulation response of polymorphonuclear leucocytes. Both rheumatoid and normal serum samples contained high concentrations of the inhibitor but the concentrations were lower in rheumatoid synovial fluids. The inhibitory activity seemed to be specific for peroxidase as the fluids did not inhibit beta-glucuronidase activity. A protein of relative molecular mass (Mr) 150 kd was purified from synovial fluid by affinity chromatography on myeloperoxidase-Sepharose. It is concluded that serum and synovial fluid contain a novel myeloperoxidase inhibitor, which acts by binding to myeloperoxidase and thereby prevents myeloperoxidase releasing oxidative products in serum. Images PMID:1647755

  14. Cytolytic activity in T cell clones derived from human synovial rheumatoid membrane: inhibition by synovial fluid.

    PubMed Central

    Miltenburg, A M; Van Laar, J M; De Kuiper, P; Daha, M R; Breedveld, F C

    1990-01-01

    A panel of T cell clones was derived from the synovial membrane of a patient with rheumatoid arthritis (RA). We investigated whether T cell clones with cytolytic properties were present and whether T cell cytotoxicity was influenced by the presence of synovial fluid. These issues were studied using anti-CD3 and lectin-induced cytotoxicity assays. The majority of the T cell clones derived from the synovial membrane showed cytotoxic properties although non-cytotoxic clones were also found. Three clones (N11, N6 and N15) showed strong cytotoxicity (more than 40% lysis at an effector-to-target cell ratio of 10:1) whereas three clones (N16, N4 and N14) were non-cytotoxic (less than 20% lysis at an effector-to-target cell ratio of 10:1). The induction of cytotoxicity in the anti-CD3-driven system was shown to be dependent on the dose of anti-CD3 present. When synovial fluid was added to these assays a strong inhibition of cytotoxicity was found. This inhibition of cytotoxicity was found with synovial fluid samples of RA patients, as well as with non-RA synovial fluids. Both anti-CD3 and lectin-dependent cytotoxicity assays were strongly inhibited. In conclusion, T cell clones with cytotoxic activity can be isolated from rheumatoid synovial membrane. In the presence of synovial fluid these cytotoxic cells are inhibited to exert their cytotoxic function. PMID:2148285

  15. Synovial fluid analysis

    MedlinePlus

    ... and looks for crystals (in the case of gout) or bacteria Measures glucose, proteins, uric acid, and ... Bleeding in the joint after a joint injury Gout and other types of arthritis Infection in a ...

  16. Molecular heterogeneity of the SHAP-hyaluronan complex. Isolation and characterization of the complex in synovial fluid from patients with rheumatoid arthritis.

    PubMed

    Yingsung, Wannarat; Zhuo, Lisheng; Morgelin, Matthias; Yoneda, Masahiko; Kida, Daihei; Watanabe, Hideto; Ishiguro, Naoki; Iwata, Hisashi; Kimata, Koji

    2003-08-29

    We previously found that a covalent complex of SHAPs (serum-derived hyaluronan-associated proteins), the heavy chains of inter-alpha-trypsin inhibitor family molecules, with hyaluronan (HA) is accumulated in synovial fluid of patients with rheumatoid arthritis, and the complex is circulated in patient plasma at high concentrations. How the SHAP-HA complex participates in this disease is unknown. To address this question, it is essential to clarify the structural features of this macromolecule. The SHAP-HA complex purified from synovial fluid of the patients by three sequential CsCl isopycnic centrifugations was heterogeneous in density, and the fractions with different densities had distinct SHAP-to-HA ratios. Agarose gel electrophoresis and column chromatography revealed that there was no apparent difference in the size distribution of HA to which SHAPs were bound between the fractions with different densities. The SHAP-HA complex in the higher density fraction had fewer SHAP molecules per HA chain. Therefore, the difference between the fractions with different densities was due to a heterogeneous population of the SHAP-HA complex, namely the different number of SHAP molecules bound to an HA chain. Based on the SHAP and HA contents of the purified preparations, we estimated that an HA chain with a molecular weight of 2 x 106 has as many as five covalently bound SHAPs, which could give a proteinaceous multivalency to HA. Furthermore, we also found that the SHAP-HA complex tends to form aggregates, judging from the migration and elution profiles in agarose gel electrophoresis and gel filtration, respectively. The multivalent feature of the SHAP-HA complex was also confirmed by the negative staining electron micrographic images of the purified fractions. Taken together, those structural characteristics may underlie the aggregate-forming and extracellular matrix-stabilizing ability of the SHAP-HA complex. PMID:12799384

  17. Assay of Blood and Synovial Fluid of Patients With Rheumatoid Arthritis for Staphylococcus aureus Enterotoxin D: Absence of Bacteria But Presence of Its Toxin

    PubMed Central

    Ataee, Ramezan Ali; Kashefi, Reyhane; Alishiri, Gholam Hossein; Esmaieli, Davoud

    2015-01-01

    Background: Rheumatoid arthritis (RA) is the most common chronic inflammatory disease. The staphylococcal superantigens are considered as the causative agent of RA disease. Objectives: This study aimed to assess the presence of staphylococcal enterotoxin D in synovial fluid and blood of patients with RA. Patients and Methods: A total of 120 blood and SF samples of patients with RA were studied. Bacterial culture, primer pairs design, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) methods have been used to assess of the staphylococcal enterotoxin D. The data were analyzed through descriptive statistics. Results: During this study and after sequential subcultures, only 5 bacterial strains were isolated. The results of PCR showed the presence of staphylococcal enterotoxin D gene in almost 50% of SF and also in 48.4% of blood samples of patients with RA. Similarly, the ELISA method detected staphylococcal enterotoxin D in 36.16% of SF and in 33.33% of blood of patients with RA. Conclusions: The result of this study showed that a high percentage of patients with RA have shown staphylococcal enterotoxin D (superantigen D) or entD gene in SF and in blood. However, the origin of this superantigen was not clarified and no Staphylococcus aureus enterotoxin D producer was isolated. This finding indicates other role of this superantigen besides its intoxication. Therefore, staphylococcal enterotoxin D as a biomarker may provide a good model for the diagnosis and treatment of patients with RA. PMID:26870313

  18. ICPMS analysis of proteins separated by Native-PAGE: Evaluation of metaloprotein profiles in human synovial fluid with acute and chronic arthritis.

    PubMed

    Moyano, Mario F; Mariño-Repizo, Leonardo; Tamashiro, Héctor; Villegas, Liliana; Acosta, Mariano; Gil, Raúl A

    2016-07-01

    The role of trace elements bound to proteins in the etiology and pathogenesis of rheumatoid arthritis (RA) remains unclear. In this sense, the identification and detection of metalloproteins has a strong and growing interest. Metalloprotein studies are currently carried out by polyacrylamide gel electrophoresis (PAGE) associated to inductively coupled plasma mass spectrometry (ICPMS), and despite that complete information can be obtained for metals such as Fe, Cu and Zn, difficulties due to poor sensitivity for other trace elements such as Sn, As, etc, are currently faced. In the present work, a simple and fast method for the determination of trace metals bound to synovial fluid (SF) proteins was optimized. Proteins from SF (long and short-term RA) were separated in ten fractions by native PAGE, then dissolved in nitric acid and peroxide hydrogen, and analyzed by ICPMS. Fifteen metals were determined in each separated protein fraction (band). Adequate calibration of proteins molecular weight allowed stablishing which protein type were bound to different metals. PMID:27259351

  19. Expression and functional role of 1F7 (CD26) antigen on peripheral blood and synovial fluid T cells in rheumatoid arthritis patients.

    PubMed

    Muscat, C; Bertotto, A; Agea, E; Bistoni, O; Ercolani, R; Tognellini, R; Spinozzi, F; Cesarotti, M; Gerli, R

    1994-11-01

    The expression and the functional role of the CD26 (1F7) T cell surface molecule, an ectoenzyme which seems to represent a functional collagen receptor of T lymphocytes and to have a role in T cell activation, were analysed in both peripheral blood (PB) and synovial fluid (SF) T cell samples from patients with active and inactive rheumatoid arthritis (RA). Although patients with active disease displayed higher percentages of PB CD26+ CD4+ T cells than inactive RA and control subjects, CD26 antigen expression on RA SF T lymphocytes was low. The anti-1F7 binding to the T cell surface, that led to CD26 antigen modulation and enhancement of both IL-2 synthesis by, and 3H-TdR incorporation of, anti-CD3- or anti-CD2-triggered PB T cells in RA and control subjects, was unable to affect significantly both expression and functional activity of RA SF T lymphocytes. Since the 1F7 antigen spontaneously reappeared on the surface of unstimulated SF T cells after 2-5 days of culturing, the low 1F7 antigen expression of anti-1F7 in the SF T cell compartment may be the result of in vivo molecule modulation exerted by the natural ligand in the joint, with important implications for T cell activation and lymphokine synthesis. PMID:7955530

  20. Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts

    PubMed Central

    Müller-Ladner, Ulf; Ospelt, Caroline; Gay, Steffen; Distler, Oliver; Pap, Thomas

    2007-01-01

    For some time synovial fibroblasts have been regarded simply as innocent synovial cells, mainly responsible for synovial homeostasis. During the past decade, however, a body of evidence has accumulated illustrating that rheumatoid arthritis synovial fibroblasts (RASFs) are active drivers of joint destruction in rheumatoid arthritis. Details regarding the intracellular signalling cascades that result in long-term activation and synthesis of proinflammatory molecules and matrix-degrading enzymes by RASFs have been analyzed. Molecular, cellular and animal studies have identified various interactions with other synovial and inflammatory cells. This expanded knowledge of the distinct role played by RASFs in the pathophysiology of rheumatoid arthritis has moved these fascinating cells to the fore, and work to identify targeted therapies to inhibit their joint destructive potential is underway. PMID:18177509

  1. Recombinant Salmonella typhimurium outer membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)-17/IL-23 in patients with reactive arthritis and undifferentiated spondyloarthropathy.

    PubMed

    Chaurasia, S; Shasany, A K; Aggarwal, A; Misra, R

    2016-08-01

    In developing countries, one-third of patients with reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) are triggered by Salmonella typhimurium. Synovial fluid mononuclear cells (SFMCs) of patients with ReA and uSpA proliferate to low molecular weight fractions (lmwf) of outer membrane proteins (Omp) of S. typhimurium. To characterize further the immunity of Omp of Salmonella, cellular immune response to two recombinant proteins of lmwf, OmpA and OmpD of S. typhimurium (rOmpA/D-sal) was assessed in 30 patients with ReA/uSpA. Using flow cytometry, 17 of 30 patients' SF CD8(+) T cells showed significant intracellular interferon (IFN)-γ to Omp crude lysate of S. typhimurium. Of these 17, 11 showed significantly more CD8(+) CD69(+) IFN-γ T cells to rOmpA-sal, whereas only four showed reactivity to rOmpD-sal. The mean stimulation index was significantly greater in rOmpA-sal than rOmpD-sal [3·0 (1·5-6·5) versus 1·5 (1·0-2·75), P < 0·005]. Similarly, using enzyme-linked immunospot (ELISPOT) in these 17 patients, the mean spots of IFN-γ-producing SFMCs were significantly greater in rOmpA-sal than rOmpD-sal [44·9 (3·5-130·7) versus 19·25 (6-41), P < 0·05]. SFMCs stimulated by rOmpA-sal produced significantly more proinflammatory cytokines than rOmpD-sal: IFN-γ [1·44 (0·39-20·42) versus 0·72 (0·048-9·15) ng/ml, P < 0·05], interleukin (IL)-17 [28·60 (6·15-510·86) versus 11·84 (6·83-252·62) pg/ml, P < 0·05], IL-23 [70·19 (15-1161·16) versus 28·25 (> 15-241·52) pg/ml, P < 0·05] and IL-6 [59·78 (2·03-273·36) versus 10·17 (0·004-190·19) ng/ml, P < 0·05]. The rOmpA-sal-specific CD8(+) T cell response correlated with duration of current synovitis (r = 0·53, P < 0·05). Thus, OmpA of S. typhimurium is a target of SF CD8(+) T cells and drives SFMC to produce increased cytokines of the IL-17/IL-23 axis which contribute to the pathogenesis of Salmonella-triggered ReA. PMID:27060348

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

    PubMed

    Bennike, Tue Bjerg; Barnaby, Omar; Steen, Hanno; Stensballe, Allan

    2015-12-01

    Synovial fluid is present in all joint cavities, and protects the articular cartilage surfaces in large by lubricating the joint, thus reducing friction. Several studies have described changes in the protein composition of synovial fluid in patients with joint disease. However, the protein concentration, content, and synovial fluid volume change dramatically during active joint diseases and inflammation, and the proteome composition of healthy synovial fluid is incompletely characterized. We performed a normative proteomics analysis of porcine synovial fluid, and report data from optimizing proteomic methods to investigate the proteome of healthy porcine synovial fluid (Bennike et al., 2014 [1]). We included an evaluation of different proteolytic sample preparation techniques, and an analysis of posttranslational modifications with a focus on glycosylation. We used pig (Sus Scrofa) as a model organism, as the porcine immune system is highly similar to human and the pig genome is sequenced. Furthermore, porcine model systems are commonly used large animal models to study several human diseases. In addition, we analyzed the proteome of human plasma, and compared the proteomes to the obtained porcine synovial fluid proteome. The proteome of the two body fluids were found highly similar, underlining the detected plasma derived nature of many synovial fluid components. The healthy porcine synovial fluid proteomics data, human rheumatoid arthritis synovial fluid proteomics data used in the method optimization, human plasma proteomics data, and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD000935. PMID:26543887

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

    PubMed Central

    Bennike, Tue Bjerg; Barnaby, Omar; Steen, Hanno; Stensballe, Allan

    2015-01-01

    Synovial fluid is present in all joint cavities, and protects the articular cartilage surfaces in large by lubricating the joint, thus reducing friction. Several studies have described changes in the protein composition of synovial fluid in patients with joint disease. However, the protein concentration, content, and synovial fluid volume change dramatically during active joint diseases and inflammation, and the proteome composition of healthy synovial fluid is incompletely characterized. We performed a normative proteomics analysis of porcine synovial fluid, and report data from optimizing proteomic methods to investigate the proteome of healthy porcine synovial fluid (Bennike et al., 2014 [1]). We included an evaluation of different proteolytic sample preparation techniques, and an analysis of posttranslational modifications with a focus on glycosylation. We used pig (Sus Scrofa) as a model organism, as the porcine immune system is highly similar to human and the pig genome is sequenced. Furthermore, porcine model systems are commonly used large animal models to study several human diseases. In addition, we analyzed the proteome of human plasma, and compared the proteomes to the obtained porcine synovial fluid proteome. The proteome of the two body fluids were found highly similar, underlining the detected plasma derived nature of many synovial fluid components. The healthy porcine synovial fluid proteomics data, human rheumatoid arthritis synovial fluid proteomics data used in the method optimization, human plasma proteomics data, and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD000935. PMID:26543887

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

    PubMed Central

    Gajewska, Joanna; Rzodkiewicz, Przemysław; Wojtecka-Łukasik, Elżbieta

    2016-01-01

    Objectives Leptin is an adipose cells derived hormone that regulates energy homeostasis within the body. Energy metabolism of immune cells influences their activity within numerous pathological states, but the effect of leptin on these cells in unclear. On the one hand, it was observed that leptin induces neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils exposed to leptin did not display detectable Ca2+ ions mobilization or β2-integrin upregulation. In this study, we investigated the effect of leptin on the redox homeostasis in lymphocytes and neutrophils. Material and methods Neutrophils and lymphocytes were isolated by density-gradient centrifugation of blood from healthy volunteers. Cells were cultured with or without leptin (100 ng/ml for lymphocytes and 500 ng/ml for neutrophils) or with or without synovial fluid (85%) for 0–72 h. Culture media were not changed during incubation. Cells were homogenized and homogenate was frozen until laboratory measurements. Redox homeostasis was assessed by the reduced glutathione (GSH) vs. oxidized glutathione (GSSG) ratio and membrane lipid peroxidation evaluation. Results Lymphocytes cultured with leptin and synovial fluid showed a significant increase of the GSSG level. The GSSG/GSH ratio increased by 184 ±37%. In neutrophils incubated in a similar environment, the GSSG/GSH ratio increased by just 21 ±7%, and the effect was observed irrespectively of whether they were exposed to leptin or synovial fluid or both together. Neither leptin nor synovial fluid influenced lipid peroxidation in neutrophils, but in lymphocytes leptin intensified lipid peroxidation. Conclusions Leptin altered the lymphocytes, but not neutrophils redox state. Because firstly neutrophils are anaerobic cells and have just a few mitochondria and secondly lymphocytes have typical aerobic metabolism, the divergence of our data supports the hypothesis that leptin induces oxidative stress by modulation of mitochondria

  5. A chemotactic inhibitor in synovial fluid.

    PubMed Central

    Matzner, Y; Partridge, R E; Babior, B M

    1983-01-01

    Synovial fluid was found to contain an inhibitor of neutrophil chemotaxis. The activity of this inhibitor was masked in native synovial fluid, but could be detected in fluid in which complement had been deactivated by mild heating. The inhibitor was most effective against the chemotactic activity of zymosan-activated serum (C5ades arg). It had little effect when N-formyl-methionyl-leucyl-phenylalanine served as chemoattractant. Inhibition was not the result of a direct effect on the neutrophils, since incubation of cells with synovial fluid did not alter their chemotactic response. The inhibitory activity was destroyed by boiling the synovial fluid or treating it with trypsin, suggesting that it is a protein (or proteins); it was not affected by hyaluronidase treatment. Gel filtration revealed that the inhibitor was present in native as well as decomplemented synovial fluid, and that its molecular weight was in the vicinity of 25,000. It is proposed that this inhibitory activity plays a role in the regulation of the inflammatory response in joints. PMID:6840801

  6. Identification of α1-Antitrypsin as a Potential Candidate for Internal Control for Human Synovial Fluid in Western Blot

    PubMed Central

    Wang, Shaowei; Zhou, Jingming; Wei, Xiaochun; Li, Pengcui; Li, Kai; Wang, Dongming; Wei, Fangyuan; Zhang, Jianzhong; Wei, Lei

    2015-01-01

    Western blot of synovial fluid has been widely used for osteoarthritis (OA) research and diagnosis, but there is no ideal loading control for this purpose. Although β-actin is extensively used as loading control in western blot, it is not suitable for synovial fluid because it is not required in synovial fluid as a cytoskeletal protein. A good loading control for synovial fluid in OA studies should have unchanged content in synovial fluids from normal and OA groups, because synovial fluid protein content can vary with changes in synovial vascular permeability with OA onset. In this study, we explore the potential of using α1-antitripsin (A1AT) as loading control for OA synovial fluid in western blot. A1AT level is elevated in inflammatory conditions such as rheumatoid arthritis (RA). Unlike RA, OA is a non-inflammation disease, which does not induce A1AT. In this study, we identified A1AT as an abundant component of synovial fluid by Mass Spectrometry and confirmed that the level of A1AT is relative constant between human OA and normal synovial fluid by western blot and ELISA. Hence, we proposed that A1AT may be a good loading control for western blot in human OA synovial fluid studies provided that pathological conditions such as RA or A1AT deficiency associated liver or lung diseases are excluded. PMID:26594594

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

    PubMed Central

    CEDERGREN, J; FORSLUND 2, T; SUNDQVIST 2, T; SKOGH 1, T

    2002-01-01

    The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure l-arginine and l-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess’ reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0·001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. l-arginine was elevated in SF compared to serum (257 ± 78 versus 176 ± 65 µmol/l, P = 0·008), whereas a slight increase in l-citrulline (33 ± 11 versus 26 ± 9 µmol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19·2 ± 20·7 versus 8·6 ± 6·5 µmol/l, P = 0·054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis. PMID:12296866

  8. Proteomic analysis of human osteoarthritis synovial fluid

    PubMed Central

    2014-01-01

    Background Osteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography. Results We identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples. Conclusions We present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the

  9. Identification of hydroxyapatite crystals in synovial fluid.

    PubMed

    Halverson, P B; McCarty, D J

    1979-04-01

    A semiquantitative technique employing (14C) ethane-1-hydroxy 1, -1-diphosphonate (EHDP) binding has been used to detect crystals, presumably hydroxyapatite, in human synovial fluid samples which were handled to prevent the formation of artifactual mineral phase. Binding material was found in 29% of non-inflammatory and in none of inflammatory joint fluids. Nuclide binding material was strongly correlated with the presence of CPPD crystals and with radiographic evidence of cartilaginous degeneration. PMID:106859

  10. [LE cells in synovial fluid: prevalence and diagnostic usefulness in rheumatic diseases].

    PubMed

    Puszczewicz, Mariusz; Białkowska-Puszczewicz, Grazyna

    2010-01-01

    This study was undertaken to determine the prevalence of LE cells in synovial fluid and their importance for the diagnosis of rheumatic disease. Synovial fluid was obtained from 631 patients: 31 with systemic lupus erythematosus (SLE), 337 with rheumatoid arthritis (RA), 4 with Still's disease, 9 with systemic scleroderma (SS), 27 with the overlap syndrome (RA/SLE), 132 with ankylosing spondylitis (AS), 57 with Reiter's syndrome, and 34 with psoriatic arthritis (PA). The fluid was centrifuged, precipitate smears were done and were May-Grünwald-Giemsa stained for cytologic assessment. The supernatant was collected for antinuclear antibody (ANA) testing. Physicochemical and serologic properties of the synovial fluid were routinely determined. All synovial fluids demonstrated signs of inflammation. The presence of LE cells was ascertained in five patients with SLE and nine patients with the overlap syndrome. In these cases, LE cells were accompanied by ANA. In addition, hematoxylin bodies were revealed in SLE patients. LE cells were observed in 2.6% of patients with RA but were not accompanied by ANA. Patients with SS, Still's disease, AS, Reiter's syndrome, and PA tested negative for LE cells. It appears from these results that LE cells are rarely present in the synovial fluid of patients with rheumatic diseases. In contrast, they occur in more than 40% of patients with the overlap syndrome and may thus be regarded as important for the diagnosis of this condition. PMID:21365954

  11. Hypoxia, mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis.

    PubMed

    Fearon, Ursula; Canavan, Mary; Biniecka, Monika; Veale, Douglas J

    2016-07-01

    Synovial proliferation, neovascularization and leukocyte extravasation transform the normally acellular synovium into an invasive tumour-like 'pannus'. The highly dysregulated architecture of the microvasculature creates a poor oxygen supply to the synovium, which, along with the increased metabolic turnover of the expanding synovial pannus, creates a hypoxic microenvironment. Abnormal cellular metabolism and mitochondrial dysfunction thus ensue and, in turn, through the increased production of reactive oxygen species, actively induce inflammation. When exposed to hypoxia in the inflamed joint, immune-inflammatory cells show adaptive survival reactions by activating key proinflammatory signalling pathways, including those mediated by hypoxia-inducible factor-1α (HIF-1α), nuclear factor κB (NF-κB), Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Notch, which contribute to synovial invasiveness. The reprogramming of hypoxia-mediated pathways in synovial cells, such as fibroblasts, dendritic cells, macrophages and T cells, is implicated in the pathogenesis of rheumatoid arthritis and other inflammatory conditions, and might therefore provide an opportunity for therapeutic intervention. PMID:27225300

  12. Cartilage extracellular matrix metabolism differs in serum and synovial fluid.

    PubMed

    Martin, James A; Wilkey, Andrew L; Brand, Richard A

    2002-01-01

    Most cartilage explant culture studies assume conventional serum-supplemented growth media are biologically equivalent to the natural synovial fluid which baths cartilage in vivo. Few studies have systematically compared the effects of serum versus synovial fluid in culture. To address this assumption we conducted a series of studies to determine if cartilage matrix synthesis is significantly different in serum-based versus synovial fluid-based media. Normal bovine cartilage explants were cultured in DMEM either alone or supplemented with bovine serum or bovine synovial fluid. Matrix synthesis was measured with radiolabeling techniques. We then compared responses to insulin-like growth factor I (IGF-I, a stimulator of matrix synthesis), and interleukin-1beta (IL-1beta, an inhibitor of matrix synthesis). We observed significantly lower matrix synthesis activity in synovial fluid versus serum. Caution shoud be used in extrapolating studies of cartilage grown in media supplemented with serum rather than synovial fluid. PMID:12843702

  13. An altered repertoire of T cell receptor V gene expression by rheumatoid synovial fluid T lymphocytes.

    PubMed

    Lunardi, C; Marguerie, C; So, A K

    1992-12-01

    The pattern of T cell receptor V gene expression by lymphocytes from rheumatoid synovial fluid and paired peripheral blood samples was compared using a polymerase chain reaction (PCR)-based assay. Eight rheumatoid arthritis (RA) patients who had varying durations of disease (from 2 to 20 years) were studied. In all patients there was evidence of a different pattern of V gene expression between the two compartments. Significantly increased expression of at least one V alpha or V beta gene family by synovial fluid T cells was observed in all the patients studied. Three different V alpha (V alpha 10, 15 and 18) and three V beta (V beta 4, 5 and 13) families were commonly elevated. Sequencing of synovial V beta transcripts demonstrated that the basis of increased expression of selected V gene families in the synovial fluid was due to the presence of dominant clonotypes within those families, which constituted up to 53% of the sequences isolated from one particular synovial V gene family. There were considerable differences in the NDJ sequences found in synovial and peripheral blood T cell receptor (TCR) transcripts of the same V beta gene family. These data suggest that the TCR repertoire in the two compartments differs, and that antigen-driven expansion of particular synovial T cell populations is a component of rheumatoid synovitis, and is present in all stages of the disease. PMID:1458680

  14. The Rheological Properties of the Biopolymers in Synovial Fluid

    NASA Astrophysics Data System (ADS)

    Krause, Wendy E.; Klossner, Rebecca R.; Wetsch, Julie; Oates, Katherine M. N.; Colby, Ralph H.

    2005-03-01

    The polyelectrolyte hyaluronic acid (HA, hyaluronan), its interactions with anti-inflammatory drugs and other biopolymers, and its role in synovial fluid are being studied. We are investigating the rheological properties of sodium hyaluronate (NaHA) solutions and an experimental model of synovial fluid (comprised of NaHA, and the plasma proteins albumin and γ-globulins). Steady shear measurements on bovine synovial fluid and the synovial fluid model indicate that the fluids are highly viscoeleastic and rheopectic (stress increases with time under steady shear). In addition, the influence of anti-inflammatory agents on these solutions is being explored. Initial results indicate that D-penicillamine and hydroxychloroquine affect the rheology of the synovial fluid model and its components. The potential implications of these results will be discussed.

  15. Rheological characterization of an artificial synovial fluid.

    PubMed

    Casentini, G; Di Paola, L; Marrelli, L; Palma, F

    2005-07-01

    Rheological measurements on two classes of artificial synovial fluids have been carried out in the attempt to get a suitable but cheap lubricant for wear tests of prosthetic materials. Fluids of both classes are solutions of hyaluronic acid (HA) that, for one class, is dissolved into a simple Ringer solution whereas, for the other class, into a mixture of human serum and Ringer solution. Similar rheological properties have been observed for both classes of fluids. Experimental results have been interpreted by two classical models that are commonly used in the literature to describe the rheological behavior of colloidal systems and of polymer solutions with high entanglement density, respectively. The quality of correlations shows that, at high HA concentrations, entangled structures are largely present and cannot be neglected. PMID:16049905

  16. Identification of the advanced glycation end products N -carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis

    PubMed Central

    Drinda, S; Franke, S; Canet, C; Petrow, P; Brauer, R; Huttich, C; Stein, G; Hein, G

    2002-01-01

    Background: Generation of advanced glycation end products (AGEs) is an inevitable process in vivo and can be accelerated under pathological conditions such as oxidative stress. In serum and synovial fluid of patients with rheumatoid arthritis (RA) raised AGE levels have been found. Objective: To determine the presence of N -carboxymethyllysine (CML; marker of oxidative stress) in RA synovial tissue by immunohistology. Methods: Frozen synovial tissue samples from 10 patients with RA and eight controls (four patients without joint disease and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline phosphatase (chromogen fuchsin). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20. Results: CML was detected in the synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive immunostaining for CML, whereas B cells were negative. Staining in OA synovial sublining was weak compared with RA. Conclusions: CML was detected for the first time in RA and OA synovial tissue. Different patterns of immunostaining in RA and OA and the presence of CML on macrophages and T cells, suggest a role for CML in the pathogenesis of RA. This might be due to presentation of new epitopes which can maintain or even trigger an autoimmune response. PMID:12006318

  17. Single-molecule imaging of hyaluronan in human synovial fluid

    NASA Astrophysics Data System (ADS)

    Kappler, Joachim; Kaminski, Tim P.; Gieselmann, Volkmar; Kubitscheck, Ulrich; Jerosch, Jörg

    2010-11-01

    Human synovial fluid contains a high concentration of hyaluronan, a high molecular weight glycosaminoglycan that provides viscoelasticity and contributes to joint lubrication. In osteoarthritis synovial fluid, the concentration and molecular weight of hyaluronan decrease, thus impairing shock absorption and lubrication. Consistently, substitution of hyaluronan (viscosupplementation) is a widely used treatment for osteoarthritis. So far, the organization and dynamics of hyaluronan in native human synovial fluid and its action mechanism in viscosupplementation are poorly characterized at the molecular level. Here, we introduce highly sensitive single molecule microscopy to analyze the conformation and interactions of fluorescently labeled hyaluronan molecules in native human synovial fluid. Our findings are consistent with a random coil conformation of hyaluronan in human synovial fluid, and point to specific interactions of hyaluronan molecules with the synovial fluid matrix. Furthermore, single molecule microscopy is capable of detecting the breakdown of the synovial fluid matrix in osteoarthritis. Thus, single molecule microscopy is a useful new method to probe the structure of human synovial fluid and its changes in disease states like osteoarthritis.

  18. Sphingolipids in Human Synovial Fluid - A Lipidomic Study

    PubMed Central

    Kosinska, Marta Krystyna; Liebisch, Gerhard; Lochnit, Guenter; Wilhelm, Jochen; Klein, Heiko; Kaesser, Ulrich; Lasczkowski, Gabriele; Rickert, Markus; Schmitz, Gerd; Steinmeyer, Juergen

    2014-01-01

    Articular synovial fluid (SF) is a complex mixture of components that regulate nutrition, communication, shock absorption, and lubrication. Alterations in its composition can be pathogenic. This lipidomic investigation aims to quantify the composition of sphingolipids (sphingomyelins, ceramides, and hexosyl- and dihexosylceramides) and minor glycerophospholipid species, including (lyso)phosphatidic acid, (lyso)phosphatidylglycerol, and bis(monoacylglycero)phosphate species, in the SF of knee joints from unaffected controls and from patients with early (eOA) and late (lOA) stages of osteoarthritis (OA), and rheumatoid arthritis (RA). SF without cells and cellular debris from 9 postmortem donors (control), 18 RA, 17 eOA, and 13 lOA patients were extracted to measure lipid species using electrospray ionization tandem mass spectrometry - directly or coupled with hydrophilic interaction liquid chromatography. We provide a novel, detailed overview of sphingolipid and minor glycerophospholipid species in human SF. A total of 41, 48, and 50 lipid species were significantly increased in eOA, lOA, and RA SF, respectively when compared with normal SF. The level of 21 lipid species differed in eOA SF versus SF from lOA, an observation that can be used to develop biomarkers. Sphingolipids can alter synovial inflammation and the repair responses of damaged joints. Thus, our lipidomic study provides the foundation for studying the biosynthesis and function of lipid species in health and most prevalent joint diseases. PMID:24646942

  19. Joint aspiration and injection and synovial fluid analysis.

    PubMed

    Courtney, Philip; Doherty, Michael

    2009-04-01

    Joint aspiration/injection and synovial fluid (SF) analysis are both invaluable procedures for the diagnosis and treatment of joint disease. This chapter addresses: (1) the indications, the technical principles and the expected benefits and risks of aspiration and injection of intra-articular corticosteroid; and (2) practical aspects relating to SF analysis, especially in relation to crystal identification. Intra-articular injection of long-acting insoluble corticosteroids is a well-established procedure that produces rapid pain relief and resolution of inflammation in most injected joints. The knee is the most common site to require aspiration, although any non-axial joint is accessible for obtaining SF. The technique requires a knowledge of basic anatomy and should not be unduly painful for the patient. Provided sterile equipment and a sensible, aseptic approach are used, it is very safe. Analysis of aspirated SF is helpful in the differential diagnosis of arthritis and is the definitive method for diagnosis of septic arthritis and crystal arthritis. The gross appearance of SF can provide useful diagnostic information in terms of the degree of joint inflammation and presence of haemarthrosis. Microbiological studies of SF are the key to the confirmation of infectious conditions. Increasing joint inflammation is associated with increased SF volume, reduced viscosity, increasing turbidity and cell count, and increasing ratio of polymorphonuclear: mononuclear cells, but such changes are non-specific and must be interpreted in the clinical setting. However, detection of SF monosodium urate and calcium pyrophosphate dihydrate crystals, even from un-inflamed joints during intercritical periods, allow a precise diagnosis of gout and of calcium pyrophosphate crystal-related arthritis. PMID:19393565

  20. Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays

    PubMed Central

    2012-01-01

    Introduction Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. Methods A pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs. Results Quantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis. Conclusion The NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level. PMID:22510425

  1. [Azlocillin--synovial fluid levels after intravenous doses].

    PubMed

    Härle, A; Ritzerfeld, W; Wiynck, G; Knoche, U

    1983-01-01

    The corresponding levels of azlocillin in serum and in synovial fluid in the knee-joint were investigated in patients who had undergone aseptic surgery of the lower limbs. The mean synovial fluid concentrations for azlocillin were determined on the basis of 30 samples. Clinically relevant azlocillin levels of approximately 40 mu g/ml were recorded in synovial fluid 10 minutes after start of a short infusion of 5 gm. These increased until about 90 minutes after commencement of antibiotic administration when the maximum level was attained. Subsequently synovial fluid levels decreased slowly and approximately 170 minutes after commencement of the short infusion the mean for serum and synovial concentrations corresponded. The results confirm that with an i.v. infusion of 5 g azlocillin levels can be attained for 3 hours in the synovial fluid that are above the break-point for this antibiotic of 64 mu g/ml. However, despite these good pharmacokinetic data it should be remembered that experience has shown that surgical reintervention is often necessary in addition in joint infections to achieve ultimate cure. PMID:6405553

  2. Persisting High Levels of Synovial Fluid Markers after Cartilage Repair

    PubMed Central

    Konttinen, Yrjö T.; Peterson, Lars; Lindahl, Anders; Kiviranta, Ilkka

    2008-01-01

    Local attempts to repair a cartilage lesion could cause increased levels of anabolic and catabolic factors in the synovial fluid. After repair with regenerated cartilage, the homeostasis of the cartilage ideally would return to normal. In this pilot study, we first hypothesized levels of synovial fluid markers would be higher in patients with cartilage lesions than in patients with no cartilage lesions, and then we hypothesized the levels of synovial fluid markers would decrease after cartilage repair. We collected synovial fluid samples from 10 patients before autologous chondrocyte transplantation of the knee. One year later, a second set of samples was collected and arthroscopic evaluation of the repair site was performed. Fifteen patients undergoing knee arthroscopy for various symptoms but with no apparent cartilage lesions served as control subjects. We measured synovial fluid matrix metalloproteinase-3 (MMP-3) and insulinlike growth factor-I (IGF-I) concentrations with specific activity and enzyme-linked immunosorbent assays, respectively. The levels of MMP-3 and IGF-I were higher in patients having cartilage lesions than in control subjects with no cartilage lesions. One year after cartilage repair, the lesions were filled with repair tissue, but the levels of MMP-3 and IGF-I remained elevated, indicating either graft remodeling or early degeneration. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18709427

  3. Importance of synovial fluid aspiration when injecting intra-articular corticosteroids

    PubMed Central

    Weitoft, T.; Uddenfeldt, P.

    2000-01-01

    OBJECTIVE—The aim of this prospective study was to find if a complete synovial fluid aspiration before injecting intra-articular corticosteroids influences the treatment result.
METHODS—The study was performed in 147 patients with rheumatoid arthritis (RA). One hundred and ninety one knees with synovitis were randomised to arthrocentesis (n=95) or no arthrocentesis (n=96) before 20 mg triamcinolone hexacetonide was injected. The duration of effect was followed up for a period of six months. All patients were instructed to contact the rheumatology department if signs and symptoms from the treated knee recurred. If arthritis could be confirmed by a clinical examination a relapse was noted.
RESULTS—There was a significant reduction of relapse in the arthrocentesis group (p=0.001).
CONCLUSION—The study shows that aspiration of synovial fluid can reduce the risk for arthritis relapse when treating RA patients with intra-articular corticosteroids. It is concluded that arthrocentesis shall be included in the intra-articular corticosteroid injection procedure.

 PMID:10700435

  4. Gene expression and activity of cartilage degrading glycosidases in human rheumatoid arthritis and osteoarthritis synovial fibroblasts

    PubMed Central

    Pásztói, Mária; Nagy, György; Géher, Pál; Lakatos, Tamás; Tóth, Kálmán; Wellinger, Károly; Pócza, Péter; György, Bence; Holub, Marianna C; Kittel, Ágnes; Pálóczy, Krisztina; Mazán, Mercédesz; Nyirkos, Péter; Falus, András; Buzas, Edit I

    2009-01-01

    Introduction Similar to matrix metalloproteinases, glycosidases also play a major role in cartilage degradation. Carbohydrate cleavage products, generated by these latter enzymes, are released from degrading cartilage during arthritis. Some of the cleavage products (such as hyaluronate oligosaccharides) have been shown to bind to Toll-like receptors and provide endogenous danger signals, while others (like N-acetyl glucosamine) are reported to have chondroprotective functions. In the current study for the first time we systematically investigated the expression of glycosidases within the joints. Methods Expressions of β-D-hexosaminidase, β-D-glucuronidase, hyaluronidase, sperm adhesion molecule 1 and klotho genes were measured in synovial fibroblasts and synovial membrane samples of patients with rheumatoid arthritis and osteoarthritis by real-time PCR. β-D-Glucuronidase, β-D-glucosaminidase and β-D-galactosaminidase activities were characterized using chromogenic or fluorogenic substrates. Synovial fibroblast-derived microvesicles were also tested for glycosidase activity. Results According to our data, β-D-hexosaminidase, β-D-glucuronidase, hyaluronidase, and klotho are expressed in the synovial membrane. Hexosaminidase is the major glycosidase expressed within the joints, and it is primarily produced by synovial fibroblasts. HexA subunit gene, one of the two genes encoding for the alpha or the beta chains of hexosaminidase, was characterized by the strongest gene expression. It was followed by the expression of HexB subunit gene and the β-D-glucuronidase gene, while the expression of hyaluronidase-1 gene and the klotho gene was rather low in both synovial fibroblasts and synovial membrane samples. Tumor growth factor-β1 profoundly downregulated glycosidase expression in both rheumatoid arthritis and osteoarthritis derived synovial fibroblasts. In addition, expression of cartilage-degrading glycosidases was moderately downregulated by proinflammatory

  5. Growth factors with heparin binding affinity in human synovial fluid

    SciTech Connect

    Hamerman, D.; Taylor, S.; Kirschenbaum, I.; Klagsbrun, M.; Raines, E.W.; Ross, R.; Thomas, K.A.

    1987-12-01

    Synovial effusions were obtained from the knees of 15 subjects with joint trauma, menisceal or ligamentous injury, or osteoarthritis. Heparin-Sepharose affinity chromatography of these synovial fluids revealed, in general, three major peaks of mitogenic activity as measured by incorporation of /sup 3/H-thymidine into 3T3 cells. Gradient elution patterns showed activities at 0.5M NaCl, which is characteristic of platelet derived growth factor, and at 1.1 M NaCl and 1.6M NaCl, indicative of acidic and basic fibroblast growth factors, respectively. The identities of these mitogenic fractions were confirmed by specific immunologic and receptor-binding assays. The presence of platelet derived, acidic and basic fibroblast growth factors in the synovial fluid may contribute to wound healing in the arthritic joint.

  6. Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation

    PubMed Central

    2014-01-01

    Introduction We previously reported that sialyl Lewisy, synthesized by fucosyltransferases, is involved in angiogenesis. Fucosyltransferase 1 (fut1) is an α(1,2)-fucosyltransferase responsible for synthesis of the H blood group and Lewisy antigens. However, the angiogenic involvement of fut 1 in the pathogenesis of rheumatoid arthritis synovial tissue (RA ST) has not been clearly defined. Methods Assay of α(1,2)-linked fucosylated proteins in RA was performed by enzyme-linked lectin assay. Fut1 expression was determined in RA ST samples by immunohistological staining. We performed angiogenic Matrigel assays using a co-culture system of human dermal microvascular endothelial cells (HMVECs) and fut1 small interfering RNA (siRNA) transfected RA synovial fibroblasts. To determine if fut1 played a role in leukocyte retention and cell proliferation in the RA synovium, myeloid THP-1 cell adhesion assays and fut1 siRNA transfected RA synovial fibroblast proliferation assays were performed. Results Total α(1,2)-linked fucosylated proteins in RA ST were significantly higher compared to normal (NL) ST. Fut1 expression on RA ST lining cells positively correlated with ST inflammation. HMVECs from a co-culture system with fut1 siRNA transfected RA synovial fibroblasts exhibited decreased endothelial cell tube formation compared to control siRNA transfected RA synovial fibroblasts. Fut1 siRNA also inhibited myeloid THP-1 adhesion to RA synovial fibroblasts and RA synovial fibroblast proliferation. Conclusions These data show that α(1,2)-linked fucosylated proteins are upregulated in RA ST compared to NL ST. We also show that fut1 in RA synovial fibroblasts is important in angiogenesis, leukocyte-synovial fibroblast adhesion, and synovial fibroblast proliferation, all key processes in the pathogenesis of RA. PMID:24467809

  7. Synovial tissue analysis for the discovery of diagnostic and prognostic biomarkers in patients with early arthritis.

    PubMed

    de Hair, Maria J H; Harty, Leonard C; Gerlag, Danielle M; Pitzalis, Costantino; Veale, Douglas J; Tak, Paul P

    2011-09-01

    Rheumatoid arthritis (RA) is a chronic disease of unspecified etiology that is manifest by persistent inflammation of the synovium. Considerable efforts have been undertaken globally to study the microenvironment of the inflamed synovium, with many encouraging and enlightening results that bring us closer to unmasking the precise etiologies of RA. Subsequent to these efforts, it has been discovered that CD68-positive macrophages present in abundance in the synovial sublining of the inflamed synovium rescind with treatments that induce clinical improvement in RA. Examination of serial synovial biopsies is now commonly used for screening purposes during early drug development, and the number of centers able to perform synovial tissue biopsy sampling according to standardized methods is increasing. Having implemented the use of serial synovial tissue biopsies to evaluate the effects of new treatments on the group level in early proof of principle studies, it is the ambition of the OMERACT Synovial Tissue Group to identify synovial diagnostic and prognostic biomarkers that could be used in individual patients. Therefore, we started a prospective study termed the Synoviomics Project aimed at the identification of novel diagnostic and prognostic synovial biomarkers. We will use straightforward and powerful technologies to analyze patient material and assess clinical parameters to identify such biomarkers. These markers may be used in the future to identify patients who are at risk of having persistent and destructive disease and to start tailor-made targeted therapies in an early phase to prevent autonomous disease progression and irreversible joint damage. PMID:21885519

  8. Gene expression profile and synovial microcirculation at early stages of collagen-induced arthritis

    PubMed Central

    Gierer, Philip; Ibrahim, Saleh; Mittlmeier, Thomas; Koczan, Dirk; Moeller, Steffen; Landes, Jürgen; Gradl, Georg; Vollmar, Brigitte

    2005-01-01

    A better understanding of the initial mechanisms that lead to arthritic disease could facilitate development of improved therapeutic strategies. We characterized the synovial microcirculation of knee joints in susceptible mouse strains undergoing intradermal immunization with bovine collagen II in complete Freund's adjuvant to induce arthritis (i.e. collagen-induced arthritis [CIA]). Susceptible DBA1/J and collagen II T-cell receptor transgenic mice were compared with CIA-resistant FVB/NJ mice. Before onset of clinical symptoms of arthritis, in vivo fluorescence microscopy of knee joints revealed marked leucocyte activation and interaction with the endothelial lining of synovial microvessels. This initial inflammatory cell response correlated with the gene expression profile at this disease stage. The majority of the 655 differentially expressed genes belonged to classes of genes that are involved in cell movement and structure, cell cycle and signal transduction, as well as transcription, protein synthesis and metabolism. However, 24 adhesion molecules and chemokine/cytokine genes were identified, some of which are known to contribute to arthritis (e.g. CD44 and neutrophil cytosolic factor 1) and some of which are novel in this respect (e.g. CC chemokine ligand-27 and IL-13 receptor α1). Online in vivo data on synovial tissue microcirculation, together with gene expression profiling, emphasize the potential role played by early inflammatory events in the development of arthritis. PMID:15987489

  9. A Normative Study of the Synovial Fluid Proteome from Healthy Porcine Knee Joints

    PubMed Central

    2015-01-01

    Synovial fluid in an articulating joint contains proteins derived from the blood plasma and proteins that are produced by cells within the joint tissues, such as synovium, cartilage, ligament, and meniscus. The proteome composition of healthy synovial fluid and the cellular origins of many synovial fluid components are not fully understood. Here, we present a normative proteomics study using porcine synovial fluid. Using our optimized method, we identified 267 proteins with high confidence in healthy synovial fluid. We also evaluated mRNA expression data from tissues that can contribute to the synovial fluid proteome, including synovium, cartilage, blood, and liver, to better estimate the relative contributions from these sources to specific synovial fluid components. We identified 113 proteins in healthy synovial fluid that appear to be primarily derived from plasma transudates, 37 proteins primarily derived from synovium, and 11 proteins primarily derived from cartilage. Finally, we compared the identified synovial fluid proteome to the proteome of human plasma, and we found that the two body fluids share many similarities, underlining the detected plasma derived nature of many synovial fluid components. Knowing the synovial fluid proteome of a healthy joint will help to identify mechanisms that cause joint disease and pathways involved in disease progression. PMID:25160569

  10. Osteoarthritis screening using Raman spectroscopy of dried human synovial fluid drops

    NASA Astrophysics Data System (ADS)

    Esmonde-White, Karen A.; Mandair, Gurjit S.; Esmonde-White, Francis W. L.; Raaii, Farhang; Roessler, Blake J.; Morris, Michael D.

    2009-02-01

    We describe the use of Raman spectroscopy to investigate synovial fluid drops deposited onto fused silica microscope slides. This spectral information can be used to identify chemical changes in synovial fluid associated with osteoarthritis (OA) damage to knee joints. The chemical composition of synovial fluid is predominately proteins (enzymes, cytokines, or collagen fragments), glycosaminoglycans, and a mixture of minor components such as inorganic phosphate crystals. During osteoarthritis, the chemical, viscoelastic and biological properties of synovial fluid are altered. A pilot study was conducted to determine if Raman spectra of synovial fluid correlated with radiological scoring of knee joint damage. After informed consent, synovial fluid was drawn and x-rays were collected from the knee joints of 40 patients. Raman spectra and microscope images were obtained from the dried synovial fluid drops using a Raman microprobe and indicate a coarse separation of synovial fluid components. Individual protein signatures could not be identified; Raman spectra were useful as a general marker of overall protein content and secondary structure. Band intensity ratios used to describe protein and glycosaminoglycan structure were used in synovial fluid spectra. Band intensity ratios of Raman spectra indicate that there is less ordered protein secondary structure in synovial fluid from the damage group. Combination of drop deposition with Raman spectroscopy is a powerful approach to examining synovial fluid for the purposes of assessing osteoarthritis damage.

  11. Immunohistological analysis of the synovial membrane: search for predictors of the clinical course in rheumatoid arthritis.

    PubMed Central

    Soden, M; Rooney, M; Whelan, A; Feighery, C; Bresnihan, B

    1991-01-01

    Immunohistological features which might predict the clinical course and outcome of rheumatoid arthritis were sought by examining multiple synovial membrane samples obtained by needle biopsy from the knee joints of 57 patients who had not received disease modifying antirheumatic drugs. Clinical measurements, but not biopsies, were repeated one year and three years after starting treatment. A correlation between both the intensity of synovial lining layer thickening and mononuclear cell infiltration and the clinical status at the time of biopsy was seen. After three years of treatment the correlations were maintained in patients who had presented and persisted with milder disease but not in patients who had presented with more active disease. PMID:1958087

  12. Comparative studies of serum and synovial fluid C reactive protein concentrations.

    PubMed Central

    Rowe, I F; Sheldon, J; Riches, P G; Keat, A C

    1987-01-01

    The relation between serum and synovial fluid (SF) C reactive protein (CRP) concentrations was investigated in a variety of arthritides, including rheumatoid arthritis (RA), psoriatic arthritis, reactive arthritis, and osteoarthritis. SF CRP levels were significantly reduced compared with serum levels in the inflammatory arthritides, but there was good correlation between serum and SF values. SF CRP values were all at the lower limit of the detectable range in osteoarthritis. In patients with RA or psoriatic arthritis followed up serially through an exacerbation of arthritis, changes in SF CRP reflected closely changes in serum CRP. In patients with RA SF/serum ratios of proteins of different molecular weight were used to derive a regression equation between SF/serum ratio and molecular mass. SF/serum values for CRP were significantly less than predicted from its molecular weight, suggesting that CRP is either being selectively bound in synovium or specifically consumed in SF and may be playing an important part in the inflammatory process in RA. PMID:3120655

  13. Synovial biopsy

    MedlinePlus

    ... the Test is Performed Synovial biopsy helps diagnose gout and bacterial infections, or rule out other infections. ... Chronic synovitis Coccidioidomycosis (a fungal infection) Fungal arthritis Gout Hemochromatosis (abnormal buildup of iron deposits) Tuberculosis Synovial ...

  14. Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features

    PubMed Central

    2012-01-01

    Introduction Psoriatic arthritis (PsA) is an autoantibody-negative immune-mediated disease in which synovial lymphoid neogenesis (LN) occurs. We determined whether LN is associated with specific patterns of inflammatory cytokine expression in paired synovial tissue (ST) and fluid (SF) samples and their potential correlation with the clinical characteristics of PsA. Methods ST and paired SF samples were obtained from the inflamed knee of PsA patients. ST samples were immunostained with CD3 (T cell), CD20 (B cell), and MECA-79 (high endothelial vessels). Total ST mRNA was extracted, and the gene expression of 21 T-cell-derived and proinflammatory cytokines were measured with quantitative real-time PCR. SF concentrations of Th1, Th2, Th17, and proinflammatory cytokines were determined with the Quantibody Human Th17 Array. Clinical and biologic data were collected at inclusion and after a median of 27 months of follow-up. Results Twenty (43.5%) of 46 patients had LN. Only two genes showed differences (Wilcoxon test, P < 0.06) in ST between LN-positive and LN-negative patients: interleukin-23A (IL-23A) (P = 0.058) and transforming growth factor-beta (TGF-β1) (P = 0.050). IL-23A expression was higher, and TGF-β1 expression was lower in LN-positive patients. ST IL-15 mRNA showed a nonsignificant trend toward higher expression in LN-positive patients, and SF IL-15 protein levels were significantly higher in LN-positive patients (P = 0.002). In all PsA patients, IL-23A mRNA expression correlated with C-reactive protein (CRP) (r = 0.471; P = 0.001) and swollen-joint count (SJC) (r = 0.350; P = 0.018), whereas SF levels of IL-6 and CC chemokine-ligand 20 (CCL-20) correlated with CRP levels (r = 0.377; P = 0.014 and r = 0.501; P < 0.0001, respectively). Conclusions These findings suggest differences in the cytokine profile of PsA patients with LN, with a higher expression of IL-23A and IL-15 and a lower expression of TGF-β1. In the entire group of patients, IL-23 ST

  15. Tribological and Rheological Properties of a Synovial Fluid Model

    NASA Astrophysics Data System (ADS)

    Klossner, Rebecca; Liang, Jing; Krause, Wendy

    2010-03-01

    Hyaluronic acid (HA) and the plasma proteins, albumin and globulins, are the most abundant macromolecules in synovial fluid, the fluid that lubricates freely moving joints. In previous studies, bovine synovial fluid, a synovial fluid model (SFM) and albumin in phosphate buffered saline (PBS) were observed to be rheopectic---viscosity increases over time under constant shear. Additionally, steady shear experiments have a strong shear history dependence in protein-containing solutions, whereas samples of HA in PBS behaved as a ``typical'' polyelectrolyte. The observed rheopexy and shear history dependence are indicative of structure building in solution, which is most likely caused by protein aggregation. The tribology of the SFM was also investigated using nanoindenter-based scratch tests. The coefficient of frictions (μ) between the diamond nanoindenter tip and a polyethylene surface was measured in the presence of the SFM and solutions with varied protein and HA concentrations. The lowest μ is observed in the SFM, which most closely mimics a healthy joint. Finally, an anti-inflammatory drug, hydroxychloroquine, was shown to inhibit protein interactions in the SFM in rheological studies, and thus the tribological response was examined. We hypothesize that the rheopectic behavior is important in lubrication regimes and therefore, the rheological and tribological properties of these solutions will be correlated.

  16. [The test of the synovial fluid in microcrystalline joint diseases].

    PubMed

    Ortiz-Bravo, E

    1994-01-15

    The search for crystals in the synovial fluid must be carried out promptly and is very helpful in the diagnosis of microcrystalline arthropathy. If at light microscopy the fluid is negative for crystals and negative or weakly positive for alizarin red, and if the diagnosis is nevertheless suspected, analysis of the centrifuged fluid sediment facilitates the identification of crystals and increases the specificity of alizarin red (the specific stain for crystals) in the identification of apatite crystal deposits. Electronmicroscopy can the be used to confirm the presence or absence of crystals. PMID:8178070

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

    PubMed Central

    Barbieri, Alessandro; Patuzzo, Giuseppe; Tinazzi, Elisa; Argentino, Giuseppe; Beri, Ruggero; Lunardi, Claudio; Puccetti, Antonio

    2015-01-01

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

  18. Synovial biopsy

    MedlinePlus

    El-Gabalawy HS. Synovial fluid analysis, synovial biopsy, and synovial pathology. In: Firestein GS, Budd RC, Harris ED Jr., et al, eds. Kelley's Textbook of Rheumatology . 8th ed. Philadelphia, PA: Saunders Elsevier; 2008:chap 48.

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

    PubMed

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

    2016-07-01

    Differentiating septic arthritis of the pediatric hip from other causes of hip pain and effusion continues to present a diagnostic challenge for the clinician. Although septic arthritis traditionally has been reported to have a synovial white blood cell count of 75,000 cells/mm3 or greater, lower counts can be seen in this condition. In cases where a synovial sample has been obtained and the cell count falls in the intermediate range between 25,000 and 75,000 cells/mm(3), it is unclear what proportion of these cases may be truly septic hips. In this evidence-based review, we examine Heyworth et al's study focusing on the predictive value of this intermediate white cell count range in a Lyme-endemic region. PMID:27385951

  20. A rapid screen for four corticosteroids in equine synovial fluid.

    PubMed

    Agrawal, Karan; Ebel, Joseph G; Bischoff, Karyn

    2014-06-01

    Most antidoping method development in the equine industry has been for plasma and urine, though there has been recent interest in the analysis of synovial fluid for evidence of doping by intra-articular corticosteroid injection. Published methods for corticosteroid analysis in synovial fluid are primarily singleplex methods, do not screen for all corticosteroids of interest and are not adequately sensitive. The purpose of this study is to develop a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) screening method for the detection of four of the most common intra-articularly administered corticosteroids--betamethasone, methylprednisolone, methylprednisolone acetate and triamcinolone acetonide. Sample preparation consisted of protein precipitation followed by a basified liquid-liquid extraction. LC-MS-MS experiments consisted of a six-min isocratic separation using a Phenomenex Polar-RP stationary phase and a mobile phase consisting of 35% acetonitrile, 5 mM ammonium acetate and 0.1% formic acid in nanopure water. The detection system used was a triple quadrupole mass analyzer with thermospray ionization, and compounds were identified using selective reaction monitoring. The method was validated to the ISO/IEC 17025 standard, and real synovial fluid samples were analyzed to demonstrate the application of the method in an antidoping context. The method was highly selective for the four corticosteroids with limits of detection of 1-3 ng/mL. The extraction efficiency was 50-101%, and the matrix effects were 14-31%. These results indicate that the method is a rapid and sensitive screen for the four corticosteroids in equine synovial fluid, fit for purpose for equine antidoping assays. PMID:24713534

  1. Arthritis due to synovial involvement by extramedullary haematopoiesis in myelofibrosis with myeloid metaplasia.

    PubMed Central

    Heinicke, M H; Zarrabi, M H; Gorevic, P D

    1983-01-01

    A 60-year-old man presented with polyarthralgias, a psoriasiform rash, and severe elbow pain. Peripheral blood smear and bone marrow biopsy established a diagnosis of myelofibrosis with myeloid metaplasia. Biopsy of the skin lesions revealed a nonspecific dermatitis. The clinical presentation was inconsistent with psoriatic arthritis, and there was no evidence for associated gout or collagen-vascular disease. Histological examination of tissue taken at the time of synovectomy indicated elbow arthritis to be due to myeloid metaplasia involving the synovial membrane. Images PMID:6847265

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

    PubMed

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

    2016-03-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main symptom is a heightened inflammatory response in synovial tissues. To verify the anti-arthritic activities of Achyranthes aspera and its possible therapy-related factors on the pathogenesis of RA, the saponins in A. aspera root were isolated and identified to treat the collagen-induced arthritis (CIA) rats. Phytochemical analysis isolated and identified methyl caffeate, 25-S-inokosterone, 25-S-inokosterone β-D-glucopyranosyl 3-(O-β-D-glucopyranosyloxy)-oleanolate, and β-D-glucopyranosyl 3-(O-β-D-galactopyranosyl (1→2)(O-β-D-glucopyranosyloxy)-oleanolate as main compounds in the root of A. aspera. Proteomics was performed to determine the differentially expressed proteins in either inflamed or drug-treated synovium of CIA rats. Treatment resulted in dramatically decreased paw swelling, proliferation of inflammatory cells, and bone degradation. Fibrinogen, procollagen, protein disulfide-isomerase A3, and apolipoprotein A-I were all increased in inflamed synovial tissues and were found to decrease when administered drug therapy. Furthermore, Alpha-1-antiproteinase and manganese superoxide dismutase were both increased in drug-treated synovial tissues. The inhibition of RA progression shows that A. aspera is a promising candidate for future treatment of human arthritis. Importantly, the total saponins found within A. aspera are the active component. Finally, autoantigens such as fibrinogen and collagen could act as inducers of RA due to their aggravation of inflammation. Given this, it is possible that the vimentin and PDIA3 could be the candidate biomarkers specific to Achyranthes saponin therapy for rheumatoid arthritis in synovial membrane. PMID:26724776

  3. The role of lubricin in the mechanical behavior of synovial fluid

    PubMed Central

    Jay, G. D.; Torres, J. R.; Warman, M. L.; Laderer, M. C.; Breuer, K. S.

    2007-01-01

    Synovial fluid is a semidilute hyaluronate (HA) polymer solution, the rheology of which depends on HA–protein interactions, and lubricin is a HA-binding protein found in synovial fluid and at cartilage surfaces, where it contributes to boundary lubrication under load. Individuals with genetic deficiency of lubricin develop precocious joint failure. The role of lubricin in synovial fluid rheology is not known. We used a multiple-particle-tracking microrheology technique to study the molecular interactions between lubricin and HA in synovial fluid. Particles (200 nm mean diameter) embedded in normal and lubricin-deficient synovial fluid samples were tracked separately by using multiple-particle-tracking microrheology. The time-dependent ensemble-averaged mean-squared displacements of all of the particles were measured over a range of physiologically relevant frequencies. The mean-squared displacement correlation with time lag had slopes with values of unity for simple HA solutions and for synovial fluid from an individual who genetically lacked lubricin, in contrast to slopes with values less than unity (α ≈ 0.6) for normal synovial fluid. These data correlated with bulk rheology studies of the same samples. We found that the subdiffusive and elastic behavior of synovial fluid, at physiological shear rates, was absent in fluid from a patient who lacks lubricin. We conclude that lubricin provides synovial fluid with an ability to dissipate strain energy induced by mammalian locomotion, which is a chondroprotective feature that is distinct from boundary lubrication. PMID:17404241

  4. Etofenamate levels in human serum and synovial fluid following iontophoresis.

    PubMed

    Bender, T; Bariska, J; Rojkovich, B; Bálint, G

    2001-01-01

    The absorption of etofenamate (CAS 30544-47-9, Rheumon gel) by iontophoresis in 11 patients with low back pain and in 13 patients with synovitis of the knee was evaluated. During the 5-day treatment period, the test gel in a quantity corresponding to 100 mg etofenamate was applied to affected body regions every day by 20-min iontophoresis sessions. Two hours after the fifth application, the concentration of etofenamate in serum and synovial fluid (in patients who had knee joint iontophoresis) were measured by HPLC. Iontophoresis of etofenamate into the lumbar region as well as to the knee joint resulted in consistent serum levels: 219 +/- 136.3 micrograms/l and 191 +/- 84.6 micrograms/l, respectively. In patients with synovitis of the knee, the synovial level of etofenamate (368 +/- 109.2 micrograms/l) was almost twice as high than the serum concentration. The authors conclude that with topical application of etofenamate by iontophoresis the drug appears not only in the serum but also--with higher levels--in the synovial fluid. PMID:11455681

  5. Role of the netrin system of repellent factors on synovial fibroblasts in rheumatoid arthritis and osteoarthritis.

    PubMed

    Schubert, T; Denk, A; Mägdefrau, U; Kaufmann, S; Bastone, P; Lowin, T; Schedel, J; Bosserhoff, A K

    2009-01-01

    Changes in the expression of repellent factors, i.e., Netrins and their receptors, may be responsible for the invasive behavior of the synovial tissue cells in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). This study was carried out to analyze the expression of Netrins and their receptors in synovial cells of patients with RA, OA, and control subjects without synovial inflammation. Quantitative RT-PCR was performed to measure the expression of Netrin-1, -3, -4, Neogenin, DCC, UNC5A-D. The influence of Netrin-1 on synovial fibroblasts (SF) was analyzed by determining proliferation, migration, and their ability to organize collagen. SF expressed all repellent factors of the Netrin family. When comparing SF of healthy donors to patients with RA and OA, a stronger expression of UNC5B (4 fold) and UNC5C (769 fold) in RA and OA was found, whereas expression of the other molecules revealed no significant differences. Treating the SF-cells with recombinant Netrin-1 resulted in inhibition of migration of RA- and OA-SFs whereas control cells were not affected. The stronger expression of UNC5B and UNC5C receptors might contribute to the disordered phenotype of RA- and OA-SFs. Addition of Netrin-1 reduces the migratory ability of SFs, potentially by repulsion, as seen in neuronal cells in embryonic development. Due to its function, Netrin-1 may constitute a novel target in the treatment of OA and RA. PMID:19822088

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

    PubMed Central

    MURAKAMI, Kohei; MAEDA, Shingo; YONEZAWA, Tomohiro; MATSUKI, Naoaki

    2016-01-01

    The activity of matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fluids (SF) sampled from dogs with joint disorders was investigated by gelatin zymography and densitometry. Pro-MMP-2 showed similar activity levels in dogs with idiopathic polyarthritis (IPA; n=17) or canine rheumatoid arthritis (cRA; n=4), and healthy controls (n=10). However, dogs with cranial cruciate ligament rupture (CCLR; n=5) presented significantly higher pro-MMP-2 activity than IPA and healthy dogs. Meanwhile, dogs with IPA exhibited significantly higher activity of pro- and active MMP-9 than other groups. Activity levels in pro- and active MMP-9 in cRA and CCLR dogs were not significantly different from those in healthy controls. Different patterns of MMP-2 and MMP-9 activity may reflect the differences in the underlying pathological processes. PMID:26902805

  7. Surfactants identified in synovial fluid and their ability to act as boundary lubricants.

    PubMed Central

    Hills, B A; Butler, B D

    1984-01-01

    Thin-layer chromatography has been used to identify phospholipids extracted from canine synovial fluid, the major component (45%) being phosphatidyl choline (PC). The extracts and their components have been shown to be surface active in reducing the surface tension of water and to be readily adsorbed to hydrophilic solids, whose surfaces then become hydrophobic. These adsorbed monolayers of synovial surfactant were then found to be excellent boundary lubricants in vitro, reducing the coefficient of kinetic friction (mu) in the dry state and under physiological loading by up to 97% for extracts and 99% for PC alone, reaching mu = 0.01. Surface-active phospholipid is put forward as the possible active ingredient in joint lubrication and shown to be consistent with previous biochemical studies to elucidate its identity. The model essentially follows the classical Hardy model for boundary lubrication imparted by surfactants. It is discussed in relation to a new approach in providing artificial lubrication and facilitating tissue release in patients with arthritis. PMID:6476922

  8. Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a murine model of rheumatoid arthritis.

    PubMed

    Matsuo, Yusuke; Mizoguchi, Fumitaka; Saito, Tetsuya; Kawahata, Kimito; Ueha, Satoshi; Matsushima, Kouji; Inagaki, Yutaka; Miyasaka, Nobuyuki; Kohsaka, Hitoshi

    2016-02-12

    Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP and wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G2/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA. PMID:26806309

  9. Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks: a cross-sectional study

    PubMed Central

    2014-01-01

    Introduction Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans. Methods RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model. Results Tissue samples from 58 synovial sites were obtained from 25 patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate Spearman’s ρ = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman’s ρ = 0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.31). IL-6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman’s ρ = 0.50), BME score (P = 0.04, approximate Spearman’s ρ = 0.31) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.35). MIP-1β was associated with CDUS activity (P = 0.02, approximate Spearman’s ρ = 0.38) and RAMRIS synovitis scores (P = 0.02, approximate Spearman’s ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance. Conclusions The association between

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

    PubMed

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

    2016-04-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment. PMID:26552406

  11. [Sonic hedgehog (SHH) promotes the proliferation of synovial fibroblasts of rats with collagen-induced arthritis].

    PubMed

    Li, Hui; Qin, Suping; Sun, Dexu; Pan, Wei; Li, Xiangyang; Kong, Fanyun; Zhen, Kuiyang; Tang, Renxian

    2016-05-01

    Objective To investigate the effect of sonic hedgehog (SHH) on the proliferation of synovial fibroblasts (SFs). Methods The serum samples were collected from 30 rheumatoid arthritis (RA) patients, 30 systemic lupus erythematosus (SLE) patients, 30 ankylosing spondylitis (AS) patients and 30 healthy subjects. The concentrations of serum SHH were detected by ELISA. Collagen induced arthritis (CIA) were developed by type 2 collagen in Sprague-Dawley rats. The SFs were isolated from knee synovial tissues of CIA rats, and then identified by the detection of vimentin by immunofluorescence technique. Before and 72 hours after blocking SHH-glioma-associated oncogene 1 (Gli-1) signaling pathway with GANT61, the expression level of SHH in SFs was detected by Western blotting, and the proliferation of SFs was examined with CCK-8 assay. Results The level of serum SHH in the RA patients was remarkably higher than that in the SLE, AS patients and the healthy controls. In the CIA rats, the expression of SHH in SFs in vitro was higher than that in the healthy control rats. After 72-hour treatment of GANT61 to block SHH-Gli-1 signaling pathway, the expression level of SHH protein in SFs from CIA rats was reduced, and meanwhile the proliferation of the SFs was inhibited. Conclusion SHH plays an important role in the proliferation of SFs and could be used as a potential therapeutic target for RA. PMID:27126942

  12. Synovial fluid dynamics with small disc perforation in temporomandibular joint.

    PubMed

    Xu, Y; Zhan, J; Zheng, Y; Han, Y; Zhang, Z; Xi, Y; Zhu, P

    2012-10-01

    The articular disc plays an important role as a stress absorber in joint movement, resulting in stress reduction and redistribution in the temporomandibular joint (TMJ). The flow of synovial fluid in the TMJ may follow a regular pattern during movement of the jaw. We hypothesised that the regular pattern is disrupted when the TMJ disc is perforated. By computed tomography arthrography, we studied the upper TMJ compartment in patients with small disc perforation during jaw opening-closing at positions from 0 to 3 cm. Finite element fluid dynamic modelling was accomplished to analyse the pattern of fluid flow and pressure distribution during the movements. The results showed that the fluid flow in the upper compartment generally formed an anticlockwise circulation but with local vortexes with the jaw opening up to 2 cm. However, when the jaw opening-closing reached 3 cm, an abnormal flow field and the fluid pressure change associated with the perforation may increase the risk of perforation expansion or rupture and is unfavourable for self-repair of the perforated disc. PMID:22582815

  13. Arthritis, a complex connective and synovial joint destructive autoimmune disease: animal models of arthritis with varied etiopathology and their significance.

    PubMed

    Naik, S R; Wala, S M

    2014-01-01

    Animal models play a vital role in simplifying the complexity of pathogenesis and understanding the indefinable processes and diverse mechanisms involved in the progression of disease, and in providing new knowledge that may facilitate the drug development program. Selection of the animal models has to be carefully done, so that there is morphologic similarity to human arthritic conditions that may predict as well as augment the effective screening of novel antiarthritic agents. The review describes exclusively animal models of rheumatoid arthritis (RA) and osteoarthritis (OA). The development of RA has been vividly described using a wide variety of animal models with diverse insults (viz. collagen, Freund's adjuvant, proteoglycan, pristane, avridine, formaldehyde, etc.) that are able to simulate/trigger the cellular, biochemical, immunological, and histologic alterations, which perhaps mimic, to a great extent, the pathologic conditions of human RA. Similarly, numerous methods of inducing animal models with OA have also been described (such as spontaneous, surgical, chemical, and physical methods including genetically manipulated animals) which may give an insight into the events of alteration in connective tissues and their metabolism (synovial membrane/tissues along with cartilage) and bone erosion. The development of such arthritic animal models may throw light for better understanding of the etiopathogenic mechanisms of human arthritis and give new impetus for the drug development program on arthritis, a crippling disease. PMID:25121375

  14. The effect of leptin on the respiratory burst of human neutrophils cultured in synovial fluid

    PubMed Central

    Rzodkiewicz, Przemysław; Gajewska, Joanna; Wojtecka-Łukasik, Elżbieta

    2015-01-01

    Objectives Leptin is a hormone responsible for nutritional status and immune competence coordination. In rheumatoid arthritis (RA) increased leptin levels were observed in both serum and synovial fluid. Its influence on development of the disease still remains unclear. So far, research on leptin's influence on the emission of reactive oxygen intermediates (ROI) measured with chemiluminescence (CL) has provided unclear and contradictory results. In this study, we evaluated the influence of leptin on oxidative activity of neutrophils isolated from blood of healthy volunteers and cultured in different amounts of synovial fluid (SF) from patients with RA. Material and methods Neutrophils’ oxidative metabolism was measured by two types of CL. The first one, luminol-dependent CL (CL-lum), allows one to determine phagocytic activity and the level of ROI generated in a myeloperoxidase-dependent manner. The second method used was lucigenin-dependent CL (CL-luc), which monitors ROI production dependent on the NADPH oxidase enzyme complex located in the cell membranes of neutrophils and enables one to determine the scope of extracellular ROI emission. Results Neutrophils stimulated by opsonized zymosan show a decrease in the level of CL-lum, proportional to the increasing concentration of both SF and serum collected from healthy donors. The observed effect of decreased CL-lum may, therefore, be dependent on the physical conditions (viscosity of fluids used). None of these experiments showed any effect of leptin on the level of CL-lum. Conclusions The present study showed that leptin does not affect the level of any of the CL types in inactive neutrophils incubated in normal serum, and it does not affect the level of oxidative activity in resting neutrophils incubated with SF. However, leptin influences extracellular ROI emission (measured by CL-luc). Leptin reduces extracellular emission of ROI, and this effect is dependent on concentration and duration of exposure to

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

    PubMed

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

    2005-01-01

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

  16. Fluorescence and UV-vis Spectroscopy of Synovial Fluids

    NASA Astrophysics Data System (ADS)

    Pinti, Marie J.; Stojilovic, Nenad; Kovacik, Mark W.

    2009-10-01

    Total joint arthroplasty involves replacing the worn cartilaginous surfaces of the joint with man-made materials that are designed to be biocompatible and to withstand mechanical stresses. Commonly these bearing materials consist of metallic alloys (TiAlV or CoCrMo) and UHMWPE. Following joint arthroplasty, the normal generation of micro-metallic wear debris particles that dislodge from the prosthesis has been shown to cause inflammatory aseptic osteolysis (bone loss) that ultimately results in the failure of the implant. Here we report our results on the novel use of Fluorescence and UV-vis spectroscopy to investigate the metallic content of synovial fluid specimens taken from postoperative total knee arthroplasties. Preliminary finding showed presence of alumina and chromium is some specimens. The ability to detect and monitor the wear rate of these implants could have far reaching implications in the prevention of metallic wear-debris induced osteolysis and impending implant failure.

  17. In vivo role of phagocytic synovial lining cells in onset of experimental arthritis.

    PubMed Central

    Van Lent, P. L.; Van den Hoek, A. E.; Van den Bersselaar, L. A.; Spanjaards, M. F.; Van Rooijen, N.; Dijkstra, C. D.; Van de Putte, L. B.; Van den Berg, W. B.

    1993-01-01

    The in vivo role of phagocytic synovial lining cells (SLC) was studied in acute experimental arthritis in the mouse. SLCs were selectively depleted by injecting liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP, Clodronate). Optimal depletion of phagocytic lining cells occurred 7 days after CL2MDP liposome injection. Eliciting an immune complex-mediated arthritis in SLC-depleted knee joints largely prevented inflammation if compared to control arthritic knee joints. Joint swelling and influx of inflammatory cells into the joint cavity was markedly diminished. Cartilage damage, in this model related to influx of inflammatory cells, was significantly decreased. Reduced influx of inflammatory cells (mainly polymorphonuclear neutrophils) was correlated to a decreased production of chemotactic factors as measured in washouts of arthritic joints in a two-compartment Transwell system. Interleukin-1-driven chemotactic factors seem to be involved. Interleukin-1 levels were significantly lowered in SLC-depleted arthritic knee joints as compared to controls. Injection of recombinant murine interleukin-1 in SLC-depleted knee joints caused less influx of inflammatory cells as compared to injection into control knee joints. A specific damage of CL2MDP liposome treatment to synovial blood vessels was excluded as intraarticular injection of human recombinant C5a in lining-depleted knee joints showed similar influx of inflammatory cells if compared to human recombinant C5a injection in control knee joints. This study indicates that in immune complex-mediated arthritis, phagocytic lining cells regulate the onset of the inflammatory response. Images Figure 2 Figure 3 Figure 6 Figure 8 PMID:8214013

  18. Comparing the mechanical properties of the porcine knee meniscus when hydrated in saline versus synovial fluid.

    PubMed

    Lakes, Emily H; Kline, Courtney L; McFetridge, Peter S; Allen, Kyle D

    2015-12-16

    As research progresses to find a suitable knee meniscus replacement, accurate in vitro testing becomes critical for feasibility and comparison studies of mechanical integrity. Within the knee, the meniscus is bathed in synovial fluid, yet the most common hydration fluid in laboratory testing is phosphate buffered saline (PBS). PBS is a relatively simple salt solution, while synovial fluid is a complex non-Newtonian fluid with multiple lubricating factors. As such, PBS may interact with meniscal tissue differently than synovial fluid, and thus, the hydration fluid may be an important factor in obtaining accurate results during in vitro testing. To evaluate these effects, medial porcine menisci were used to evaluate tissue mechanics in tension (n=11) and compression (n=15). In all tests, two samples from the same meniscus were taken, where one sample was hydrated in PBS and the other was hydrated in synovial fluid. Statistical analysis revealed no significant differences between the mean mechanical properties of samples tested in PBS compared to synovial fluid; however, compressive testing revealed the variability between samples was significantly reduced if samples were tested in synovial fluid. For example, the compressive Young׳s Modulus was 12.69±7.49MPa in PBS versus 12.34±4.27MPa in synovial fluid. These results indicate testing meniscal tissue in PBS will largely not affect the mean value of the mechanical properties, but performing compression testing in synovial fluid may provide more consistent results between samples and assist in reducing sample numbers in some experiments. PMID:26592438

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  20. Synovial expression of Th17-related and cancer-associated genes is regulated by the arthritis severity locus Cia10.

    PubMed

    Jenkins, E; Brenner, M; Laragione, T; Gulko, P S

    2012-04-01

    We have previously identified Cia10 as an arthritis severity and articular damage quantitative trait locus. In this study, we used Illumina RatRef-12 microarrays to analyze the expression of 21,922 genes in synovial tissues from arthritis-susceptible DA and arthritis-protected DA.ACI(Cia10) congenics with pristane-induced arthritis. 310 genes had significantly different expression. The genes upregulated in DA, and reciprocally downregulated in DA.ACI(Cia10) included IL-11, Ccl12 and Cxcl10, as well as genes implicated in Th17 responses such as IL-17A, IL-6, Ccr6, Cxcr3 and Stat4. Suppressors of immune responses Tgfb and Vdr, and inhibitors of oxidative stress were upregulated in congenics. There was an over-representation of genes implicated in cancer and cancer-related phenotypes such as tumor growth and invasion among the differentially expressed genes. Cancer-favoring genes like Ctsd, Ikbke, and Kras were expressed in increased levels in DA, whereas inhibitors of cancer phenotypes such as Timp2, Reck and Tgfbr3 were increased in DA.ACI(Cia10). These results suggest that Cia10 may control arthritis severity, synovial hyperplasia and joint damage via the regulation of the expression of cancer-related genes, inflammatory mediators and Th17-related markers. These new findings have the potential to generate new targets for therapies aimed at reducing arthritis severity and joint damage in rheumatoid arthritis. PMID:22048456

  1. Influence of Anti-inflammatory Drugs on the Rheological Properties of Synovial Fluid and Its Components

    NASA Astrophysics Data System (ADS)

    Krause, Wendy E.; Klossner, Rebecca R.; Liang, Jing; Colby, Ralph H.

    2006-03-01

    The polyelectrolyte hyaluronic acid (HA, hyaluronan), its interactions with anti-inflammatory drugs and other biopolymers, and its role in synovial fluid are being studied. We are investigating the rheological properties of sodium hyaluronate (NaHA) solutions and an experimental model of synovial fluid (comprised of NaHA, and the plasma proteins albumin and γ-globulins). Steady shear measurements on bovine synovial fluid, the synovial fluid model, and plasma protein solutions indicate that the fluids are rheopectic (stress increases with time under steady shear). In addition, the influence of anti-inflammatory agents on these solutions is being explored. Initial results indicate that D-penicillamine and hydroxychloroquine (HCQ) affect the rheology of the synovial fluid model and its components. While HCQ has no effect on the viscosity of NaHA solutions, it inhibits/suppresses the observed rheopexy of the synovial fluid model and plasma protein solutions. In contrast, D-penicillamine has a complex, time dependent effect on the viscosity of NaHA solutions,---reducing the zero shear rate viscosity of a 3 mg/mL NaHA (in phosphate buffered saline) by ca. 40% after 44 days. The potential implications of these results will be discussed.

  2. Quality assurance for synovial fluid examination for crystals: an improved method

    PubMed Central

    McGill, N.; McGill, V.

    1997-01-01

    OBJECTIVE—To determine the best method of preparing synovial fluid specimens for use in quality assurance (QA) surveys designed to assess accuracy of crystal identification.
METHODS—A previously published method (A) was compared with a new method (B) in the setting of a QA survey. Ten Australian, one New Zealand, and one Hong Kong hospital laboratories took part in the survey. Each laboratory examined six different synovial fluid specimens prepared using method A (first round) and a separate six specimens using method B (second round). In method A, a drop of synovial fluid on a glass slide was surrounded by a rim of Ultramount, sealed with a coverslip, and distributed. The participating laboratory did not need to perform any processing of the specimen before examination. In method B, a capillary tip was filled with synovial fluid, heat sealed, and distributed. The fluid was expelled onto a glass slide in preparation for examination after arrival in the participating laboratory.
RESULTS—Using method A 36 of 71 (51%) of the specimens were rated as satisfactory, compared with 53 of 61 (87%) of the specimens using method B (Fisher's exact test, p<0.001).
CONCLUSIONS—An improved method of preparation of synovial fluid specimens for QA surveys is described. Using the new method it is feasible to perform a synovial fluid QA survey covering a large area (Australasia).

 PMID:9306876

  3. Th1-Induced CD106 Expression Mediates Leukocytes Adhesion on Synovial Fibroblasts from Juvenile Idiopathic Arthritis Patients

    PubMed Central

    Luciani, Cristina; Capone, Manuela; Rossi, Maria Caterina; Chillà, Anastasia; Santarlasci, Veronica; Mazzoni, Alessio; Cimaz, Rolando; Liotta, Francesco; Maggi, Enrico; Cosmi, Lorenzo; Del Rosso, Mario; Annunziato, Francesco

    2016-01-01

    This study tested the hypothesis that subsets of human T helper cells can orchestrate leukocyte adhesion to synovial fibroblasts (SFbs), thus regulating the retention of leukocytes in the joints of juvenile idiopathic arthritis (JIA) patients. Several cell types, such as monocytes/macrophages, granulocytes, T and B lymphocytes, SFbs and osteoclasts participate in joint tissue damage JIA. Among T cells, an enrichment of classic and non-classic Th1 subsets, has been found in JIA synovial fluid (SF), compared to peripheral blood (PB). Moreover, it has been shown that IL-12 in the SF of inflamed joints mediates the shift of Th17 lymphocytes towards the non-classic Th1 subset. Culture supernatants of Th17, classic and non-classic Th1 clones, have been tested for their ability to stimulate proliferation, and to induce expression of adhesion molecules on SFbs, obtained from healthy donors. Culture supernatants of both classic and non-classic Th1, but not of Th17, clones, were able to induce CD106 (VCAM-1) up-regulation on SFbs. This effect, mediated by tumor necrosis factor (TNF)-α, was crucial for the adhesion of circulating leukocytes on SFbs. Finally, we found that SFbs derived from SF of JIA patients expressed higher levels of CD106 than those from healthy donors, resembling the phenotype of SFbs activated in vitro with Th1-clones supernatants. On the basis of these findings, we conclude that classic and non-classic Th1 cells induce CD106 expression on SFbs through TNF-α, an effect that could play a role in leukocytes retention in inflamed joints. PMID:27123929

  4. Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors

    PubMed Central

    Gao, W; McGarry, T; Orr, C; McCormick, J; Veale, D J; Fearon, U

    2016-01-01

    Background Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by synovitis and destruction of articular cartilage/bone. Janus-kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway is implicated in the pathogenesis of PsA. Objectives To examine the effect of tofacitinib (JAK inhibitor) on proinflammatory mechanisms in PsA. Methods Primary PsA synovial fibroblasts (PsAFLS) and ex vivo PsA synovial explants were cultured with tofacitinib (1 µM). PhosphoSTAT3 (pSTAT3), phosphoSTAT1 (pSTAT1), suppressor of cytokine signaling-3 (SOCS3), protein inhibitor of activated Stat3 (PIAS3) and nuclear factor kappa B cells (NFκBp65) were quantified by western blot. The effect of tofacitinib on PsAFLS migration, invasion, Matrigel network formation and matrix metallopeptidase (MMP)2/9 was quantified by invasion/migration assays and zymography. Interleukin (IL)-6, IL-8, IFN-gamma-inducible protein 10 (IP-10) monocyte chemoattractant protein (MCP)-1, IL-17, IL-10, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were assessed by ELISA. Results Tofacitinib significantly decreased pSTAT3, pSTAT1, NFκBp65 and induced SOCS3 and PIAS3 expression in PsAFLS and synovial explant cultures (p<0.05). Functionally, PsAFLS invasion, network formation and migration were inhibited by tofacitinib (all p<0.05). In PsA explant, tofacitinib significantly decreased spontaneous secretion of IL-6, IL-8, MCP-1, MMP9/MMP2, MMP3 (all p<0.05) and decreased the MMP3/TIMP3 ratio (p<0.05), with no effect observed for IP-10 or IL-10. Conclusions This study further supports JAK-STAT inhibition as a therapeutic target for the treatment of PsA. PMID:26353790

  5. Hyaluronan Inhibits Tlr-4-Dependent RANKL Expression in Human Rheumatoid Arthritis Synovial Fibroblasts

    PubMed Central

    Hirabara, Shinya; Ishiguro, Naoki; Kojima, Toshihisa

    2016-01-01

    The Toll-like receptor (TLR) signaling pathway is activated in synovial fibroblast cells in patients with rheumatoid arthritis (RA). The receptor activator of nuclear factor-κB (RANK) and its ligand, RANKL, are key molecules involved in the differentiation of osteoclasts and joint destruction in RA. Hyaluronan (HA) is a major extracellular component and an important immune regulator. In this study, we show that lipopolysaccharide (LPS) stimulation significantly increases RANKL expression via a TLR-4 signaling pathway. We also demonstrate that HA suppresses LPS-induced RANKL expression, which is dependent on CD44, but not intercellular adhesion molecule-1 (ICAM-1). Our study provides evidence for HA-mediated suppression of TLR-4-dependent RANKL expression. This could present an alternative target for the treatment of destructed joint bones and cartilages in RA. PMID:27054952

  6. Synovial Regulatory T Cells Occupy a Discrete TCR Niche in Human Arthritis and Require Local Signals To Stabilize FOXP3 Protein Expression

    PubMed Central

    Giannakopoulou, Eirini; Lom, Hannah; Wedderburn, Lucy R.

    2015-01-01

    Although there is great interest in harnessing the immunosuppressive potential of FOXP3+ regulatory T cells (Tregs) for treating autoimmunity, a sizeable knowledge gap exists regarding Treg fate in human disease. In juvenile idiopathic arthritis (JIA) patients, we have previously reported that atypical CD25+FOXP3− Treg-like cells uniquely populate the inflamed site. Intriguingly, their proportions relative to CD25+FOXP3+ Tregs associate with arthritis course, suggesting a role in disease. The ontogeny of these FOXP3− Treg-like cells is, however, unknown. In this study, we interrogated clonal relationships between CD4+ T cell subsets in JIA, using high-throughput TCR repertoire analysis. We reveal that FOXP3+ Tregs possess highly exclusive TCRβ usage from conventional T cells, in blood, and also at the inflamed site, where they are clonally expanded. Intriguingly, the repertoires of FOXP3+ Tregs in synovial fluid are highly overlapping with CD25+FOXP3− Treg-like cells, indicating fluctuations in FOXP3 expression in the inflamed joint. Furthermore, cultured synovial Tregs rapidly downregulated FOXP3 protein (but not mRNA), and this process was prevented by addition of synovial fluid from JIA patients, through an IL-6–independent mechanism. Our findings suggest that most Tregs arise from a separate lineage from conventional T cells, and that this repertoire divergence is largely maintained under chronic inflammatory conditions. We propose that subsequent Treg expansions at the inflamed site creates an environment that leads to competition for limited resources within the synovium, resulting in the destabilization of FOXP3 expression in some Tregs. PMID:26561546

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

    PubMed

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

    2015-10-01

    In this study, autoantibody responses to annexin A2 were found in 11-15% of 278 patients with Lyme disease, including in those with erythema migrans (EM), an early sign of the illness, and in those with antibiotic-responsive or antibiotic-refractory Lyme arthritis (LA), a late disease manifestation. In contrast, robust T cell reactivity to annexin A2 peptides was found only in patients with responsive or refractory LA. In LA patients, annexin A2 protein levels, which were higher in the refractory group, correlated with annexin A2 antibody levels in sera and synovial fluid. In addition, in patients with antibiotic-refractory LA who had anti-annexin A2 antibodies, synovial tissue had intense staining for annexin A2 protein, greater synovial fibroblast proliferation and more tissue fibrosis. Thus, a subset of LA patients had T and B cell responses to annexin A2, and in the refractory group, annexin A2 autoantibodies were associated with specific pathologic findings. PMID:26187145

  8. Photodynamic therapy using talaporfin sodium for synovial membrane from rheumatoid arthritis patients and collagen-induced arthritis rats.

    PubMed

    Torikai, Eiji; Kageyama, Yasunori; Kohno, Eiji; Hirano, Toru; Koide, Yukio; Terakawa, Susumu; Nagano, Akira

    2008-06-01

    We investigated the efficacy of photodynamic therapy (PDT) using talaporfin sodium as a new method of synovectomy for rheumatoid arthritis (RA). We first used RA synovial membrane (RASM) for in vitro and in vivo study. The RASM was obtained from patients with RA during total knee replacement. In the in vitro study, RA fibroblast-like synoviocytes (RASCs) obtained from the RASM were examined by fluorescent microscopy to measure the intracellular localization of talaporfin sodium. The cells were then subjected to PDT, and their viability was examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium inner salt assay. In the in vivo assay, RASM was obtained as described above, grafted onto severe combined immunodeficiency (SCID) mice and subjected to PDT. The damaged area of RASM was evaluated histologically at 1 day after PDT. Next, we performed a separate experiment using rats with collagen-induced arthritis (CIA). After intra-articular injection of talaporfin sodium, the concentration of talaporfin sodium accumulated in the CIA synovial membrane (CIASM) was compared with that in cartilage, periarticular muscle, and skin. We then performed PDT with intra-articular injection of talaporfin sodium and intra-articular irradiation. The damaged area of the CIASM was measured at 1 day after the PDT, and the articular histological and radiological changes of the ankle were observed at 56 days after the PDT. In RASM, talaporfin sodium accumulated in lysosomes in vitro, and the phototoxicity to RASCs in vitro and to RASM grafted onto SCID mice in vivo depended on the concentration of talaporfin sodium and the laser energy. In CIA rats, there was a greater accumulation of talaporfin sodium in the CIASM than in normal tissue. The CIASM was selectively damaged at 1 day after the PDT, and the bone and cartilage destruction were ameliorated at 56 days after the PDT. In conclusion, PDT using talaporfin sodium might be a new method for

  9. Elevated synovial fluid concentration of adenosine triphosphate in dogs with osteoarthritis or sodium urate-induced synovitis of the stifle.

    PubMed

    Torres, Bryan T; Jimenez, David A; Budsberg, Steven C

    2016-07-19

    Adenosine triphosphate has been shown to stimulate nociceptive nerve terminals in joints. Elevated synovial fluid adenosine triphosphate concentrations as well as a correlation between synovial fluid adenosine triphosphate concentrations and osteoarthritic knee pain has been demonstrated in humans, but not yet in dogs. This study documented elevated synovial fluid adenosine triphosphate concentrations in the stifles of dogs with secondary osteoarthritis and urate-induced synovitis, as compared to normal stifles. PMID:27432274

  10. Descriptions of therapeutic arthrocenthesis and of synovial fluid in a Nahuatl text from prehispanic Mexico.

    PubMed

    Alarcon-Segovia, D

    1980-06-01

    Paracelsus is considered to have been the first to record the viscid quality of the synovial fluid. However, his contemporary Bernardino de Sahagún, a Franciscan friar who came to Mexico shortly after the Spanish conquest, obtained from elderly Aztec Indians who spoke only Nahuatl the descriptions of therapeutic arthrocentesis and of the viscid nature of the synovial fluid. They compared the fluid from the knee joint to the viscid fluid from the leaves of the nopal cactus (Opuntia sp.). We here record their description and confirm the accuracy of their comparison. PMID:7416821

  11. Descriptions of therapeutic arthrocenthesis and of synovial fluid in a Nahuatl text from prehispanic Mexico.

    PubMed Central

    Alarcon-Segovia, D

    1980-01-01

    Paracelsus is considered to have been the first to record the viscid quality of the synovial fluid. However, his contemporary Bernardino de Sahagún, a Franciscan friar who came to Mexico shortly after the Spanish conquest, obtained from elderly Aztec Indians who spoke only Nahuatl the descriptions of therapeutic arthrocentesis and of the viscid nature of the synovial fluid. They compared the fluid from the knee joint to the viscid fluid from the leaves of the nopal cactus (Opuntia sp.). We here record their description and confirm the accuracy of their comparison. Images PMID:7416821

  12. Toll-Like Receptors Expressed by Synovial Fibroblasts Perpetuate Th1 and Th17 Cell Responses in Rheumatoid Arthritis

    PubMed Central

    Zheng, Li; Shi, Lianjie; Liu, Hongjiang; Zhang, Xuewu; Zhu, Huaqun; Tang, Sumei; Zhu, Lei; Xu, Liling; Yang, Yuqin; Li, Zhanguo

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone and cartilage erosion. Synovial fibroblast- and T cell-mediated inflammation plays crucial roles in the pathogenesis of RA. However how this inflammation is initiated, propagated, and maintained remains controversial. Here, we systemically examined the contribution of toll-like receptors (TLRs) to the inflammatory mediator production as well as Th1 and Th17 cell hyperactivity in RA. Our results show that rheumatoid arthritis synovial fibroblasts (RASF) express a series of TLRs, including TLR2, TLR3, TLR4, and TLR9, with the predominant expression of TLR3. Moreover, the expression levels of these TLRs were higher than those in osteoarthritis synovial fibroblasts (OASF). Ligation of TLR3, as well as TLR2 and TLR4, resulted in vigorous production of inflammatory cytokines, matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) in RASF, with activation of the NF-κB, MAPK, and IRF3 pathways. More important, activation of these TLRs expressed by RASF exacerbated inflammatory Th1 and Th17 cell expansion both in cell-cell contact-dependent and inflammatory cytokine-dependent manners, which induced more IFN-γ and IL-17 accumulation. Targeting TLRs may modulate the inflammation in RA and provide new therapeutic strategies for overcoming this persistent disease. PMID:24936783

  13. The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage, and synovial fibroblast invasion.

    PubMed

    Laragione, Teresina; Cheng, Kai F; Tanner, Mark R; He, Mingzhu; Beeton, Christine; Al-Abed, Yousef; Gulko, Pércio S

    2015-06-01

    Little is known about the regulation of arthritis severity and joint damage in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) have a central role in joint damage and express increased levels of the cation channel Trpv2. We aimed at determining the role of Trpv2 in arthritis. Treatment with Trpv2-specific agonists decreased the in vitro invasiveness of FLS from RA patients and arthritic rats and mice. Trpv2 stimulation suppressed IL-1β-induced expression of MMP-2 and MMP-3. Trpv2 agonists, including the new and more potent LER13, significantly reduced disease severity in KRN serum- and collagen-induced arthritis, and reduced histologic joint damage, synovial inflammation, and synovial blood vessel numbers suggesting anti-angiogenic activity. In this first in vivo use of Trpv2 agonists we discovered a new central role for Trpv2 in arthritis. These new compounds have the potential to become new therapies for RA and other diseases associated with inflammation, invasion, and angiogenesis. PMID:25869297

  14. Inhibitory effect of sodium houttuyfonate on synovial proliferation in vitro in cells from a patient with rheumatoid arthritis

    PubMed Central

    LI, JUN; ZHOU, TING; ZHAO, FUTAO

    2014-01-01

    The aim of the present study was to investigate the inhibitory effect of sodium houttuyfonate (SH) on synovial cell proliferation in vitro. Primary cells were obtained from the synovial tissue of a patient with rheumatoid arthritis (RA). The cells were divided into five treatment groups as follows: the control group (group 1), 25 μg/ml SH-treated group (group 2), 50 μg/ml SH-treated group (group 3), 100 μg/ml SH-treated group (group 4) and the 200 μg/ml SH-treated group (group 5). Following seven days of treatment, the proliferation rate of the synovial cells was then detected using an MTT assay. The expression level of proliferative synovial cells markedly decreased in the SH-treated groups in a dose-dependent manner compared with the control group. In conclusion, the present study demonstrated that SH was able to inhibit the proliferation of synovial cells obtained from a patient with RA. These results provide a potential theoretical basis for the development of a safe and effective treatment against RA in the future. PMID:24926358

  15. Assessment of glycosaminoglycan concentration in equine synovial fluid as a marker of joint disease.

    PubMed Central

    Palmer, J L; Bertone, A L; McClain, H

    1995-01-01

    A modification of a colorimetric assay was used to determine synovial fluid total and individual sulphated-glycosaminoglycan concentration in various clinical presentations of joint disease in horses. Concentrations of synovial fluid and serum sulphated-glycosaminoglycan (GAG) were measured by the 1,9-dimethylmethylene blue (DMMB) dye assay in normal horses (n = 49), horses with acute (n = 26) or chronic (n = 27) joint disease (defined by clinical, radiographic, and clinicopathological parameters), and horses with cartilaginous lesions at diagnostic arthroscopy, but with normal radiographs and synovial fluid (n = 9). Horses with acute joint disease were subdivided into moderate acute (n = 21) and severe acute (n = 5) joint disease on the basis of synovial fluid analysis and clinical examination. Horses with chronic joint disease were subdivided into mild chronic (n = 9), moderate chronic (n = 10), and severe chronic (n = 8) joint disease on the basis of synovial fluid analysis, clinical examination, and radiographic findings. The concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) were analyzed in each sample following sequential enzymatic digestion of the sample with chondroitinase or keratanase. In addition, the concentration of hyaluronate (HA) in each sample was determined by a colorimetric assay following digestion of the sample with microbial hyaluronidase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8521354

  16. On the matter of synovial fluid lubrication: implications for Metal-on-Metal hip tribology.

    PubMed

    Myant, Connor; Cann, Philippa

    2014-06-01

    Artificial articular joints present an interesting, and difficult, tribological problem. These bearing contacts undergo complex transient loading and multi axes kinematic cycles, over extremely long periods of time (>10 years). Despite extensive research, wear of the bearing surfaces, particularly metal-metal hips, remains a major problem. Comparatively little is known about the prevailing lubrication mechanism in artificial joints which is a serious gap in our knowledge as this determines film formation and hence wear. In this paper we review the accepted lubrication models for artificial hips and present a new concept to explain film formation with synovial fluid. This model, recently proposed by the authors, suggests that interfacial film formation is determined by rheological changes local to the contact and is driven by aggregation of synovial fluid proteins. The implications of this new mechanism for the tribological performance of new implant designs and the effect of patient synovial fluid properties are discussed. PMID:24462265

  17. Complement-derived leukotactic factors in inflammatory synovial fluids of humans

    PubMed Central

    Ward, Peter A.; Zvaifler, Nathan J.

    1971-01-01

    A large per cent of rheumatoid synovial fluids contain chemotactic activity for rabbit granulocytes (neutrophilic). The chemotactic activity is, in large part, related to the fifth (C5) and sixth (C6) components of human complement; a combination of physical-chemical techniques indicates the activity to be attributable to C567 and C5a, a cleavage product of C5. Many rheumatoid synovial fluids contain a C5-cleaving enzyme which, on the basis of substrate specificity and susceptibility to inhibitors, is very similar to an enzyme extractable from lysosomal granules of human and rabbit granulocytes. Inflammatory nonrheumatoid synovial fluids contain chemotactic activity that is related to cleavage products (C3a) of the third component of human complement (C3). Also found in these fluids is a C3-cleaving enzyme capable of producing C3a. Of the other synovial fluids examined, lupus fluids were remarkable by their total lack of chemotactic activity. These findings record for the first time the presence of complement-derived chemotactic factors in pathological human fluids. Images PMID:5545123

  18. Vascular perfusion kinetics by contrast-enhanced ultrasound are related to synovial microvascularity in the joints of psoriatic arthritis.

    PubMed

    Fiocco, Ugo; Stramare, Roberto; Coran, Alessandro; Grisan, Enrico; Scagliori, Elena; Caso, Francesco; Costa, Luisa; Lunardi, Francesca; Oliviero, Francesca; Bianchi, Fulvia Chieco; Scanu, Anna; Martini, Veronica; Boso, Daniele; Beltrame, Valeria; Vezzù, Maristella; Cozzi, Luisella; Scarpa, Raffaele; Sacerdoti, David; Punzi, Leonardo; Doria, Andrea; Calabrese, Fiorella; Rubaltelli, Leopoldo

    2015-11-01

    The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transducer was used in conjunction with a specific continuous mode contrast enhanced harmonic imaging technology with a second-generation sulfur hexafluoride-filled microbubbles C-agent. The examination was carried out within 1 week before arthroscopic biopsies in 32 active joints. Perfusional parameters were analyzed including regional blood flow (RBF); peak (PEAK) of the C-signal intensity, proportional to the regional blood volume (RBV); beta (β) perfusion frequency; slope (S), representing the inclination of the tangent in the origin; and the refilling time (RT), the reverse of beta. Arthroscopic synovial biopsies were targeted in the hypervascularity areas, as in the same knee recesses assessed by CEUS; the synovial cell infiltrate and vascularity (vessel density) was evaluated by IHC staining of CD45 (mononuclear cell) and CD31, CD105 (endothelial cell) markers, measured by computer-assisted morphometric analysis. In the CEUS area examined, the corresponding time-intensity curves demonstrated a slow rise time. Synovial histology showed slight increased layer lining thickness, perivascular lymphomonocyte cell infiltration, and microvascular remodeling, with marked vessel wall thickening with reduction of the vascular lumen. A significant correlation was found between RT and CD31+ as PEAK and CD105+ vessel density; RT was inversely correlated to RBF, PEAK, S, and β. The study demonstrated the association of the CEUS perfusion kinetics with the histopathological quantitative and morphologic estimation of synovial microvascular proliferation, suggesting that a CEUS imaging represents a reliable tool for the estimate of the

  19. Aberrant histone acetylation contributes to elevated interleukin-6 production in rheumatoid arthritis synovial fibroblasts.

    PubMed

    Wada, Takuma Tsuzuki; Araki, Yasuto; Sato, Kojiro; Aizaki, Yoshimi; Yokota, Kazuhiro; Kim, Yoon Taek; Oda, Hiromi; Kurokawa, Riki; Mimura, Toshihide

    2014-02-21

    Accumulating evidence indicates that epigenetic aberrations have a role in the pathogenesis of rheumatoid arthritis (RA). However, reports on histone modifications are as yet quite limited in RA. Interleukin (IL)-6 is an inflammatory cytokine which is known to be involved in the pathogenesis of RA. Here we report the role of histone modifications in elevated IL-6 production in RA synovial fibroblasts (SFs). The level of histone H3 acetylation (H3ac) in the IL-6 promoter was significantly higher in RASFs than osteoarthritis (OA) SFs. This suggests that chromatin structure is in an open or loose state in the IL-6 promoter in RASFs. Furthermore, curcumin, a histone acetyltransferase (HAT) inhibitor, significantly reduced the level of H3ac in the IL-6 promoter, as well as IL-6 mRNA expression and IL-6 protein secretion by RASFs. Taken together, it is suggested that hyperacetylation of histone H3 in the IL-6 promoter induces the increase in IL-6 production by RASFs and thereby participates in the pathogenesis of RA. PMID:24513290

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

    PubMed Central

    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. PMID:18076767

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

    PubMed

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

    2016-02-01

    The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (P<0.05). The expression peaked on day 5, remained detectable on day 40 and disappeared on day 60. No EGFP expression was detected in the other tissues and organs. The UTMD

  2. Lower expression of histamine H₄ receptor in synovial tissues from patients with rheumatoid arthritis compared to those with osteoarthritis.

    PubMed

    Yamaura, Katsunori; Oda, Manabu; Suzuki, Masahiko; Ueno, Koichi

    2012-10-01

    The aim of this study is to compare the expression level of histamine H(4) receptor (H(4)R) mRNA in synovial tissues of rheumatoid arthritis (RA) and osteoarthritis (OA) patients, and to study correlation of results with clinical characteristics of patients with RA. Synovial tissues were obtained from 7 RA and 7 OA patients undergoing artificial arthroplasty. Serum levels of erythrocyte sedimentation rate, C-reactive protein, matrix metalloproteinase-3 (MMP-3), rheumatoid factors, and cyclic citrullinated peptide antibodies were determined. The expression of H(4)R mRNA in synovial tissues was determined by real-time polymerase chain reaction. Expression of H(1)R and H(4)R mRNA were significantly lower in RA compared with OA patients (P < 0.005), while expression of H(2)R mRNA was comparable in both. While a significant negative correlation was found between H(4)R expression and serum MMP-3 concentration (r = -0.70, P < 0.05), no correlation was found between MMP-3 and H(1)R (r = -0.52) or H(2)R (r = 0.23). This study supports the supposition that H(4)R in synovial tissue may play a role in cartilage and bone destruction by influencing the secretion of MMP-3 in patients with RA. PMID:21881994

  3. Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis.

    PubMed

    Yoon, Bo Ruem; Chung, Yeon-Ho; Yoo, Su-Jin; Kawara, Kenji; Kim, Jinhyun; Yoo, In Seol; Park, Chung-Gyu; Kang, Seong Wook; Lee, Won-Woo

    2016-02-19

    B7-H3, a newly identified B7 family member, has functional duality as a co-stimulator and co-inhibitor that fine-tunes T cell-mediated immune responses. Given that B7-H3 expression on human monocytes and dendritic cells is enhanced by inflammatory cytokines, its potential inmmunoregulatory role at sites of inflammation has been suggested. Further, monocytes play crucial roles in the pathophysiology of various inflammatory disorders including autoimmune diseases; however, the immunological role of B7-H3 in rheumatoid arthritis (RA) has not been defined. Thus, we aimed to investigate the possible roles of monocyte B7-H3 in the pathogenesis of RA. Synovial monocytes, but not peripheral monocytes, in RA patients predominantly express surface B7-H3. The 4Ig isoform of B7-H3 is exclusively induced on the cell surface, whereas the 2Ig B7-H3 isoform is constitutively expressed in the intracytoplasmic region of both peripheral and synovial monocytes. B7-H3 knockdown experiments reveal that surface B7-H3 has an inhibitory effect on IFN-γ production in CD4 memory cells. Moreover, surface B7-H3 expression on synovial monocytes inversely correlates with RA clinical parameters. Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune responses and immunomodulatory roles affecting RA pathogenesis. PMID:26702052

  4. ADAMTS-4 activity in synovial fluid as a biomarker of inflammation and effusion

    PubMed Central

    Roberts, S.; Evans, H.; Wright, K.; van Niekerk, L.; Caterson, B.; Richardson, J.B.; Kumar, K.H.S.; Kuiper, J.H.

    2015-01-01

    Summary Objective To evaluate the potential of ADAMTS-4 (aggrecanase -1) activity in synovial fluid (SF) as a biomarker of knee injury and joint disease. Design We have measured ADAMTS-4 activity in the synovial fluid of 170 orthopaedic patients with different degrees of joint pathology, using a commercial ADAMTS-4 fluorescence resonance energy transfer (FRET) substrate assay. Patients were classified at arthroscopy as (i) macroscopically normal, (ii) with an injury of the meniscus, anterior cruciate ligament or chondral/osteochondral defects or (iii) with osteoarthritis, and the influence of independent factors (age, patient group, effusion and synovial inflammation) on ADAMTS-4 activity levels was assessed. Results In most patients (106/170) ADAMTS-4 activity was undetectable; ADAMTS-4 ranged from 0 to 2.8 ng/mL in synovial fluid from patients with an injury, 0–4.1 ng/mL in osteoarthritic patients and 4.0–12.3 ng/mL in patients with large effusions. Four independent variables each significantly influenced ADAMTS-4 activity in synovial fluid (all P < 0.001): age (concordance = 0.69), presence of osteoarthritis (OA) (concordance = 0.66), level of effusion (concordance = 0.78) and inflammation (concordance = 0.68). Not only did effusion influence the amount of ADAMTS-4 activity most strongly, but it also did this in an ordered manner (P < 0.001). Conclusions The main finding of this study is that ADAMTS-4 levels in synovial fluid are most strongly correlated with inflammation and severity of effusion in the knee. Further study is required to determine if it could provide a useful tool to aid clinical diagnoses, indicate treatment, to monitor progression of joint degeneration or OA or alternatively the success of treatment. PMID:26003949

  5. Expression of adhesion molecules on synovial fluid and peripheral blood monocytes in patients with inflammatory joint disease and osteoarthritis

    PubMed Central

    Koller, M; Aringer, M; Kiener, H; Erlacher, L; Machold, K; Eberl, G; Studnicka-Benke, A; Graninger, W; Smolen, J

    1999-01-01

    OBJECTIVE—To determine the presence of adhesion molecules on monocytes/macrophages (Mϕ) from peripheral blood (PB) and synovial fluid (SF) in patients with osteoarthritis (OA) and inflammatory joint diseases (rheumatoid (RA) and reactive arthritis (ReA)) in order to improve our understanding of the possible mechanisms underlying the inflammatory process.
METHODS—Whole blood and SF cells were stained with monoclonal antibodies against CD11a (LFA-1), CD15 s (sialyl-Lewis X), CD44, CD54, VLA-4, and HLA-DR counterstained with anti-CD14 antibodies as a Mϕ marker for dual fluorescence analysis by flowcytometry. 
RESULTS—On PB-Mϕ, CD15s was markedly increased in both RA as well as ReA compared with OA. Furthermore, in the PB LFA-1, CD44, and HLA-DR showed a higher surface density on Mϕ in ReA than in OA. Comparison between SF and PB showed significantly higher CD44 and CD54 expression on SF-Mϕ. These molecules play an important part in lymphocyte-Mϕ interaction.
CONCLUSION—In PB from patients with inflammatory joint diseases, Mϕ are activated, allowing recruitment into the synovial compartment. These disorders, in contrast with OA seem to be "systemic" in nature. Within the SF, different adhesion molecules are expressed on CD14+ Mϕ as compared with PB.

 PMID:10531076

  6. Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis.

    PubMed

    Yarmola, Elena G; Shah, Yash; Arnold, David P; Dobson, Jon; Allen, Kyle D

    2016-04-01

    Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker--the c-terminus telopeptide of type II collagen (CTXII)--magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide-containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 μL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed tenfold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat. PMID:26136062

  7. Differential levels of synovial fluid aggrecan aggregate components in experimental osteoarthritis and joint disuse.

    PubMed

    Ratcliffe, A; Beauvais, P J; Saed-Nejad, F

    1994-07-01

    The levels of proteoglycan aggregate components (link protein, keratan sulfate epitope, and total sulfated glycosaminoglycan) were determined in the synovial fluid lavages of dogs with experimental osteoarthritis or disuse atrophy. A model of experimental osteoarthritis was created by transection of the anterior cruciate ligament of the right knee; studies were carried out 6 and 12 weeks after surgery. Joint disuse was studied at 4 and 8 weeks after initiation of the disuse. Recovery after disuse also was studied in joints that had 3 weeks of remobilization after 4 or 8 weeks of disuse. Synovial fluid lavages from the right knee joints of untreated animals were used as controls. The concentrations of keratan sulfate epitope, sulfated glycosaminoglycan, and link protein in the synovial fluid lavages at 6 and 12 weeks after transection of the anterior cruciate were elevated compared with the control values. Similar analysis of the fluid after disuse showed that the levels of keratan sulfate epitope and sulfated glycosaminoglycan were increased compared with the control levels and the levels after transection. However, the concentration of link protein in the fluid after disuse was not significantly different from the control level. The levels of keratan sulfate epitope and sulfated glycosaminoglycan in the synovial fluid lavages after disuse with recovery were high, but the levels of link protein remained low. The results indicate that the catabolism of proteoglycan aggregates in articular cartilage during early osteoarthritis and disuse is different. The determination of keratan sulfate epitope in synovial fluid lavages appears to provide a relatively general indication of proteoglycan catabolism, whereas increased levels of link protein may be more indicative of cartilage degeneration. PMID:7520485

  8. Mosaic chromosomal aberrations in synovial fibroblasts of patients with rheumatoid arthritis, osteoarthritis, and other inflammatory joint diseases

    PubMed Central

    Kinne, Raimund W; Liehr, Thomas; Beensen, Volkmar; Kunisch, Elke; Zimmermann, Thomas; Holland, Heidrun; Pfeiffer, Robert; Stahl, Hans-Detlev; Lungershausen, Wolfgang; Hein, Gert; Roth, Andreas; Emmrich, Frank; Claussen, Uwe; Froster, Ursula G

    2001-01-01

    Chromosomal aberrations were comparatively assessed in nuclei extracted from synovial tissue, primary-culture (P-0) synovial cells, and early-passage synovial fibroblasts (SFB; 98% enrichment; P-1, P-4 [passage 1, passage 4]) from patients with rheumatoid arthritis (RA; n = 21), osteoarthritis (OA; n = 24), and other rheumatic diseases. Peripheral blood lymphocytes (PBL) and skin fibroblasts (FB) (P-1, P-4) from the same patients, as well as SFB from normal joints and patients with joint trauma (JT) (n = 4), were used as controls. Analyses proceeded by standard GTG-banding and interphase centromere fluorescence in situ hybridization. Structural chromosomal aberrations were observed in SFB (P-1 or P-4) from 4 of 21 RA patients (19%), with involvement of chromosome 1 [e.g. del(1)(q12)] in 3 of 4 cases. In 10 of the 21 RA cases (48%), polysomy 7 was observed in P-1 SFB. In addition, aneusomies of chromosomes 4, 6, 8, 9, 12, 18, and Y were present. The percentage of polysomies was increased in P-4. Similar chromosomal aberrations were detected in SFB of OA and spondylarthropathy patients. No aberrations were detected in i) PBL or skin FB from the same patients (except for one OA patient with a karyotype 45,X[10]/46,XX[17] in PBL and variable polysomies in long-term culture skin FB); or ii) synovial tissue and/or P-1 SFB of normal joints or of patients with joint trauma. In conclusion, qualitatively comparable chromosomal aberrations were observed in synovial tissue and early-passage SFB of patients with RA, OA, and other inflammatory joint diseases. Thus, although of possible functional relevance for the pathologic role of SFB in RA, these alterations probably reflect a common response to chronic inflammatory stress in rheumatic diseases. PMID:11549374

  9. EGFP gene transfection into the synovial joint tissues of rats with rheumatoid arthritis by ultrasound-mediated microbubble destruction

    PubMed Central

    JING, XIANG-XIANG; LIU, JIE; YANG, BING-ANG; FU, SHAO-QING; WU, TANG-NA; WANG, DONG-LIN

    2014-01-01

    The aim of the present study was to explore the feasibility of enhancing green fluorescent protein (EGFP) gene transfection into the synovial joint tissues of rats with rheumatoid arthritis (RA) by ultrasound-mediated microbubble destruction. An optimal SonoVue dose was determined using 40 normal rats categorized into five groups according to the various doses of microbubbles used. At 1 week after ultrasound irradiation, the rats were sacrificed. Damage to the joint synovial tissues was observed with hematoxylin and eosin histopathological staining under a microscope. A further 44 normal rats were used to establish a rat model of RA, and were then categorized into four groups: EGFP, ultrasound + EGFP, microbubbles + EGFP and ultrasound + microbubbles + EGFP. The last group was irradiated with ultrasound for 10 min following the injection of 300 μl SonoVue and 10 μg EGFP into the joint cavity. Rats were sacrificed after 3 days and synovial tissue was collected from the knee joints for observation of EGFP with fluorescence microscopy and analysis by quantitative polymerase chain reaction. EGFP expression was observed in the synovial tissues of all groups. However, high EGFP expression levels were observed in the ultrasound + microbubbles + EGFP group. No statistically significant differences (P>0.05) were observed in the EGFP expression levels between the EGFP, ultrasound + EGFP and microbubbles + EGFP groups. However, EGFP expression levels in the EGFP, ultrasound + EGFP and microbubbles + EGFP groups significantly differed (P<0.05) from that in the ultrasound + microbubbles + EGFP group. Therefore, ultrasound-mediated microbubble destruction improved EGFP transfection efficiency into the joint synovial tissues of rats with RA. PMID:24940446

  10. VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis

    PubMed Central

    Yi, Jin-Ping; Wu, Yu-Zhang; Yu, Nan; Yu, Zhi-Wu; Xie, Fu-Yuan; Yuan, Quan

    2016-01-01

    Background Our study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA). Material/Methods Clinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded. Results The genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05). Conclusions Our study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA. PMID:26825024

  11. Raman spectroscopy of dried synovial fluid droplets as a rapid diagnostic for knee joint damage

    NASA Astrophysics Data System (ADS)

    Esmonde-White, Karen A.; Mandair, Gurjit S.; Raaii, Farhang; Roessler, Blake J.; Morris, Michael D.

    2008-02-01

    Human synovial fluid droplets were investigated using drop deposition in combination with Raman spectroscopy. Following informed consent, synovial fluid was obtained from forty human patients with various severities of knee pain and/or osteoarthritis at the time of knee arthroscopy or total joint replacement. Synovial fluid was aspirated from the knee joint of each patient and stored at -80°C until examination by near-infrared Raman spectroscopy. Synovial fluid aspirates from the knee joint of each patient were deposited onto a clean fused silica microscope slide and the droplet dried under ambient laboratory conditions. Each droplet was illuminated by a line-focused or a ring-focused 785 nm laser. As the droplet dries, biofluid components segregated based on solubility differences and a deposit that is spatially heterogeneous was made. Spectra taken from the droplet edges and center were dominated by protein bands and showed the presence of at least two protein moieties in the droplet. Band area and band height ratios (1410 cm -1/1450 cm -1) showed the greatest change between specimens from patients with mild/early osteoarthritis compared to those with severe/late stage osteoarthritis. The greatest differences were found in the center of the droplet, which contains more soluble protein components than the edges.

  12. Localization of /sup 99m/Tc methylene disphosphonate within synovial fluid in osteosarcoma

    SciTech Connect

    Sandler, M.S.; Heyman, S.; Watts, H.

    1984-08-01

    Extraosseous uptake of /sup 99m/Tc phosphate bone scanning agents has been reported in a wide variety of lesions, including malignant effusions. A case of uptake of bone scanning agent within synovial fluid in a joint involved with osteosarcoma is reported.

  13. Orally incoculated Salmonella typhimurium is detected in the lymph nodes and synovial fluid of swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella is a foodborne pathogen that has been associated with illnesses from the consumption of meat products. Traditional carcass sampling techniques fail to account for contamination via atypical carcass reservoirs such as lymph nodes and synovial fluid that may harbor Salmonella. In this two-p...

  14. Identification of Synovial Fluid Biomarkers for Knee Osteoarthritis and Correlation with Radiographic Assessment.

    PubMed

    Monibi, Farrah; Roller, Brandon L; Stoker, Aaron; Garner, Bridget; Bal, Sonny; Cook, James L

    2016-04-01

    Osteoarthritis (OA) is a costly and debilitating condition that is typically not diagnosed early enough to prevent progression of disease. The purpose of this study was to evaluate synovial fluid from knees with and without OA for potential markers of joint inflammation and degradation and to correlate these findings with radiographic severity of disease. With Institutional Review Board approval, synovial fluid samples were collected before the patient undergoing total knee arthroplasty. Control knees (n = 3) were patients younger than 30 years of age with no history of anterior cruciate ligament, posterior cruciate ligament, or meniscal injury, and no surgical history for either knee. Weight-bearing, anterior-posterior radiographic views were used to determine radiographic OA severity using the modified Kellgren and Lawrence scale. Synovial fluid samples from 18 patients (21 knees) were analyzed using a multiplex assay. Matrix metalloproteinase (MMP)-1 (p < 0.001), interleukin (IL)-6 (p < 0.013), IL-8 (p < 0.024), and Chemokine (C-C motif) ligand 5 (CCL5) (p < 0.006) were significantly higher in the synovial fluid of OA patients compared with normal patients. The radiographic score was significantly higher in patients with OA compared with normal knees (p < 0.002). MMP-1 had a moderate positive correlation with MMP-2, IL-6, IL-8, and CCL5. IL-6 had a strong positive correlation with IL-8 and a moderate positive correlation with MMP-2. Monocyte chemotactic protein 1 had a moderate positive correlation with IL-6 and a strong positive correlation with IL-8. Radiographic scores had a strong positive correlation with IL-6 and IL-8 and a moderate positive correlation with MCP-1. These data provide novel and clinically relevant information for the investigation of synovial fluid biomarkers for knee OA. PMID:25927354

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

    PubMed Central

    Boechat, Antônio Luiz; de Oliveira, Catiúscia Padilha; Tarragô, Andrea Monteiro; da Costa, Allyson Guimarães; Malheiro, Adriana; Guterres, Silvia Stanisçuaski; Pohlmann, Adriana Raffin

    2015-01-01

    Background Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%–16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules. Objective The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution. Methods Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments. Results Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the

  16. Cytochemical demonstration of constitutive H2O2 production by macrophages in synovial tissue from rats with adjuvant arthritis.

    PubMed Central

    Hoffstein, S. T.; Gennaro, D. E.; Meunier, P. C.

    1988-01-01

    Generation of toxic oxygen metabolites by inflammatory cells is considered to be one of the mechanisms by which inflammation produces tissue injury. This concept is based on in vitro studies of purified leukocyte populations because it has not been possible to assess production of these metabolites in tissues. In order to determine whether or not inflammatory cells in tissue generate H2O2, the authors modified an earlier cytochemical method for the localization of H2O2. The incubation medium consists of 0.5 mM CeCl3 in a Hepes-buffered balanced salt solution with Cl- as the only anion. Synovial tissue from the knees of normal and 16-day adjuvant arthritic rats was incubated in this medium for 30 minutes and then fixed and processed for electron microscopy. No H2O2 reaction product was visible in normal synovium. In contrast, patchy deposits of H2O2 reaction product were seen adjacent to a subpopulation of synovial lining macrophages in synovium from inflamed knee joints. These data show that rat synovial macrophages are capable of generating H2O2 when appropriately stimulated and that such a stimulus is present in adjuvant arthritis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3257356

  17. Towards a stratified targeted approach with biologic treatments in rheumatoid arthritis: role of synovial pathobiology.

    PubMed

    Astorri, Elisa; Nerviani, Alessandra; Bombardieri, Michele; Pitzalis, Costantino

    2015-01-01

    Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disease affecting diarthrodial joints and extra-articular tissues; in the absence of an effective treatment, it is characterized by persistent symmetrical and erosive synovitis which leads to structural joint damage and lifelong disability. Several autoantibodies have been associated with RA such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). B cells have been shown to play a crucial role in the pathogenesis of RA by producing autoantibodies and promoting synovial inflammation through antigen presentation, T cells activation and cytokines production [1]. Although biologic agents have notably improved disease outcome and patients' quality of life, currently around 30-40% of subjects do not respond to treatment and the mechanisms leading to resistance are still not known [2]. For this reason, new prognostic biomarkers and predictors of response are needed. We and others have postulated that the development of biomarkers for patients' stratification prior therapeutic intervention may be possible through a better understanding of the different histopathological patterns present both in early and established individual RA patient and the related underlying cellular and molecular mechanisms. To date, Tumor Necrosis Factor (TNF)-α has been shown to be one of the master elements of inflammation in RA; however, even though therapies aimed at blocking this key cytokine have emerged as a major tool in the treatment of RA, a large proportion of patients (approximately 30-40%) do not achieve a meaningful clinical response assessed by either the American College of Rheumatology (ACR) or the European League Against Rheumatism (EULAR) criteria. The same limitation can be applied to the use of rituximab, a chimeric monoclonal antibody directed against CD20, which is uniquely expressed by all B-lymphocytes during the maturation process from late stage pro-B cells to memory cells. The

  18. HMGB1–LPS complex promotes transformation of osteoarthritis synovial fibroblasts to a rheumatoid arthritis synovial fibroblast-like phenotype

    PubMed Central

    Qin, Y; Chen, Y; Wang, W; Wang, Z; Tang, G; Zhang, P; He, Z; Liu, Y; Dai, S-M; Shen, Q

    2014-01-01

    It is generally believed that some inflammatory antigens can recognize Toll-like receptors on synovial fibroblasts (SFs) and then activate downstream signals, leading to the formation of RASFs and inducing rheumatoid arthritis (RA). The objective of the current work was to study on the hypothesis that outer PAMP (LPS) binds to the inner DAMP (HMGB1) and becomes a complex that recognizes TLRs/RAGE on SFs, thus initiating a signaling cascade that leads to the secretion of inflammatory cytokines and chemokines, production of tissue-destructive enzymes, and formation of RASFs, finally resulting in RA. Osteoarthritis synovial fibroblasts (OASFs) were co-cultured with HMGB1–LPS complex in vitro for five generations to induce the transformation of human SFs to RA-like SFs (tOASFs). Then, changes of tOASFs in cell cycle and apoptosis–autophagy balance were investigated in vitro, and the pathogenicity of tOASFs was evaluated in a SCID mouse model in vivo. In vitro cell cycle analysis showed more tOASFs passing through the G1/S checkpoint and moving to S or G2 phase. Flow cytometry and confocal microscopy showed that apoptosis was reduced and autophagy was enhanced significantly in tOASFs as compared with those in OASFs. The expression of certain receptors and adhesion molecules in tOASFs was upregulated. In vivo experiments showed that tOASFs attached to, invaded, and degraded the co-implanted cartilage. In addition, histochemistry showed excessive proliferation of tOASFs and the expression of matrix metalloproteinases (MMPs). Based on the above findings, we conclude that HMGB1–LPS complex could promote the formation of RASFs. PMID:24556692

  19. Bacterial arthritis.

    PubMed

    Ho, G

    1991-08-01

    In this review of the 1990 septic arthritis literature, we revisit synovial fluid leukocytosis, examine the utility of synovial fluid glucose and protein measurements, and look at the levels of two cytokines, tumor necrosis factor and interleukin-1, in infected joint fluids. We see the many faces of gonococcal arthritis and the ravages of septic arthritis when the host has rheumatoid arthritis. Should we recommend antibiotic prophylaxis for the rheumatoid patient with a prosthetic joint who is undergoing a procedure that leads to transient bacteremia? What are some of the salient features of septic arthritis when it involves the sternoclavicular or sacroiliac joints? We also look at some unusual microorganisms, eg, group C Streptococcus, Streptococcus viridans, Listeria monocytogenes, Pseudomonas cepacia, Pseudomonas maltophilia, and Neisseria sicca. In patients with acquired immunodeficiency syndrome, we encounter reports of septic arthritis, osteomyelitis, and spinal epidural abscess caused by opportunistic microorganisms. Two unusual sites of infection include the C1-2 lateral facet joint and subacromial bursa without involvement of the glenohumeral joint. Finally, we examine how to drain a septic knee: the orthopedic point of view. PMID:1911055

  20. Impact of synovial fluid flow on temperature regulation in knee cartilage.

    PubMed

    Moghadam, Mohamadreza Nassajian; Abdel-Sayed, Philippe; Camine, Valérie Malfroy; Pioletti, Dominique P

    2015-01-21

    Several studies have reported an increase of temperature in cartilage submitted to cyclic sinusoidal loading. The temperature increase is in part due to the viscous behavior of this tissue, which partially dissipates the input mechanical energy into heat. While the synovial fluid flow within the intra-articular gap and inside the porous cartilage is supposed to play an important role in the regulation of the cartilage temperature, no specific study has evaluated this aspect. In the present numerical study, a poroelastic model of the knee cartilage is developed to evaluate first the temperature increase in the cartilage due to dissipation and second the impact of the synovial fluid flow in the cartilage heat transfer phenomenon. Our results showed that, the local temperature is effectively increased in knee cartilage due to its viscous behavior. The synovial fluid flow cannot significantly preventing this phenomenon. We explain this result by the low permeability of cartilage and the moderate fluid exchange at the surface of cartilage under deformation. PMID:25488136

  1. Tribological performance of the biological components of synovial fluid in artificial joint implants

    NASA Astrophysics Data System (ADS)

    Ghosh, Subir; Choudhury, Dipankar; Roy, Taposh; Moradi, Ali; Masjuki, H. H.; Pingguan-Murphy, Belinda

    2015-08-01

    The concentration of biological components of synovial fluid (such as albumin, globulin, hyaluronic acid, and lubricin) varies between healthy persons and osteoarthritis (OA) patients. The aim of the present study is to compare the effects of such variation on tribological performance in a simulated hip joint model. The study was carried out experimentally by utilizing a pin-on-disk simulator on ceramic-on-ceramic (CoC) and ceramic-on-polyethylene (CoP) hip joint implants. The experimental results show that both friction and wear of artificial joints fluctuate with the concentration level of biological components. Moreover, the performance also varies between material combinations. Wear debris sizes and shapes produced by ceramic and polyethylene were diverse. We conclude that the biological components of synovial fluid and their concentrations should be considered in order to select an artificial hip joint to best suit that patient.

  2. Assay of synovial fluid parameters: hyaluronan concentration as a potential marker for joint diseases.

    PubMed

    Praest, B M; Greiling, H; Kock, R

    1997-10-31

    Synovial fluids from the knees of patients with degenerative joint disease (n = 29), osteoarthritis (n = 16), diabetic arthropathy (n = 12), gout (n = 7) and acute inflammatory joint disease (n = 7) were investigated by high-performance size-exclusion chromatography combined with multiangle laser light scattering detection and differential refractometry. These data were compared with the viscosities of the same samples measured by rotation viscometry with one low shear rate, as well as with C reactive protein. The median value of the weight-average molecular weight of hyaluronan in synovial fluids, which differed less than the viscosity of these groups, varied between 1.09 x 10(6) g/mol (range 0.849-1.63 x 10(6) g/mol) (acute-inflammatory joint disease) and 1.91 x 10(6) g/mol (range 1.06-3.48 x 10(6) g/mol) (degenerative joint disease). The correlation between viscosity and hyaluronan concentration was much better than between viscosity and weight-average molecular weight. Changes in C reactive protein concentration were correlated with the disease activity. The concentration of hyaluronan was significantly higher in the cases of degenerative joint disease and diabetic arthropathy. These results suggest that synovial fluid concentration of hyaluronan is appropriate as a prognostic value in the evaluation of different kinds of joint diseases. PMID:9437540

  3. Lack of Detection of Human Retrovirus-5 Proviral DNA in Synovial Tissue and Blood Specimens From Individuals With Rheumatoid Arthritis or Osteoarthritis

    PubMed Central

    PIPER, KERRYL E.; HANSSEN, ARLEN D.; LEWALLEN, DAVID G.; MATTESON, ERIC L.; OSMON, DOUGLAS R.; DUFFY, MARY C.; HAGAN, ROCHELLE A.; STECKELBERG, JAMES M.; PATEL, ROBIN

    2006-01-01

    Objective Prior studies have suggested an association of human retrovirus 5 with rheumatoid arthritis. The purpose of this study was to determine if human retrovirus-5 proviral DNA is present in synovial tissue and blood specimens from patients with rheumatoid arthritis or osteoarthritis, or those without joint disease. Methods Synovial tissue and whole blood from 75 patients with rheumatoid arthritis, 75 patients with osteoarthritis, and 50 patients without a primary arthritis diagnosis were assayed by real-time quantitative polymerase chain reaction (PCR) using primers that amplify a 186-bp fragment of human retrovirus-5 proviral DNA. Results A total of 200 tissue specimens, 200 mononuclear cells, and 196 of 200 granulocyte specimens tested negative for human retrovirus-5 proviral DNA. No association between human retrovirus 5 and rheumatoid arthritis or osteoarthritis (P = 0.516) was identified. Granulocyte specimens from 4 patients, 2 with rheumatoid arthritis and 2 with osteoarthritis, yielded a low positive human retrovirus-5 proviral DNA signal (83–1,365 copies of human retrovirus-5 proviral DNA/ml blood). Conclusion Contrary to prior reports, we did not find an association between human retrovirus 5 and rheumatoid arthritis or osteoarthritis using a real-time PCR assay. Our findings are consistent with the recent finding that human retrovirus 5 is actually rabbit endogenous retrovirus H. PMID:16463423

  4. Increased activity and expression of histone deacetylase 1 in relation to tumor necrosis factor-alpha in synovial tissue of rheumatoid arthritis

    PubMed Central

    2010-01-01

    Introduction The purpose of this study was to investigate the profile of histone deacetylase (HDAC) expression in the synovial tissue of rheumatoid arthritis (RA) compared with that of normal control and osteoarthritis (OA), and to examine whether there is a link between HDAC activity and synovial inflammation. Methods HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of total synovial tissue surgically obtained from normal, OA and RA joints. The level of cytoplasmic tumor necrosis factor a (TNFα) fraction was measured by ELISA. Total RNA of synovial tissue was used for RT-PCR of HDAC1-8. In synovial fibroblasts from RA (RASFs), the effects of TNFα on nuclear HDAC activity and class I HDACs (1, 2, 3, 8) mRNA expressions were examined by quantitative real-time PCR. The protein expression and distribution of class I HDACs were examined by Western blotting. Results Nuclear HDAC activity was significantly higher in RA than in OA and normal controls and correlated with the amount of cytoplasmic TNFα. The mRNA expression of HDAC1 in RA synovial tissue was higher than in OA and normal controls, and showed positive correlation with TNFα mRNA expression. The protein level of nuclear HDAC1 was higher in RA synovial tissue compared with OA synovial tissue. Stimulation with TNFα significantly increased the nuclear HDAC activity and HDAC1 mRNA expression at 24 hours and HDAC1 protein expression at 48 hours in RASFs. Conclusions Our results showed nuclear HDAC activity and expression of HDAC1 were significantly higher in RA than in OA synovial tissues, and they were upregulated by TNFα stimulation in RASFs. These data might provide important clues for the development of specific small molecule HDAC inhibitors. PMID:20609223

  5. Ultrasound Assessment of Synovial Thickness of Some of the Metacarpophalangeal Joints of Hand in Rheumatoid Arthritis Patients and the Normal Population

    PubMed Central

    Hussain Manik, Zuhudha; George, John; Sockalingam, Sargunan

    2016-01-01

    Objective. To compare ultrasound synovial thickness of the 2nd, 3rd and 4th metacarpophalangeal joints (MCPJ) in a group of patients with proven rheumatoid arthritis (RA) and a control group of normal individuals. Materials and Methods. This is a cross-sectional study comprising 30 rheumatoid arthritis patients and 30 healthy individuals. Ultrasound scans were performed at the dorsal side of 2nd, 3rd, and 4th MCPJ of both hands in RA patients and the healthy individuals. Synovial thickness was measured according to quantitative method. The synovial thickness of RA patients and healthy individuals was compared and statistical cut-off was identified. Results. Maximum synovial thickness was most often detected at the radial side of the 2nd MCPJ and 3rd MCPJ and ulnar side of the 4th MCPJ of both hands which is significantly higher (p < 0.05) in RA patients compared to healthy individuals. With high specificity (96%) and sensitivity (90%) the optimum cut-off value to distinguish RA patients and healthy individuals' synovial thickness differs for the radial side of the 2nd and 3rd MCPJ and ulnar side of the 4th MCPJ. Conclusion. Patients with early RA appear to exhibit a characteristic pattern of synovitis which shows radial side predominance in the 2nd and 3rd MCPJ and ulnar side in the 4th MCPJ. PMID:27190682

  6. Multicomponent T2 Analysis of Articular Cartilage With Synovial Fluid Partial Volume Correction

    PubMed Central

    Liu, Fang; Chaudhary, Rajeev; Block, Walter F.; Samsonov, Alexey; Kijowski, Richard

    2016-01-01

    Purpose To investigate the use of a three-pool model to account for the confounding effects of synovial fluid on multicomponent T2 analysis of articular cartilage using Multicomponent Driven Equilibrium Single Shot Observation of T1 and T2 (mcDESPOT). Materials and Methods mcDESPOT was performed on the knee of eight asymptomatic volunteers and eight patients with osteoarthritis at 3.0T with multicomponent T2 maps created using the two-pool model and a three-pool model containing a nonexchanging synovial fluid water pool. The fraction of the fast-relaxing water component (FF) and the T2 relaxation times for the fast-relaxing (T2F) and slow-relaxing (T2S) water components were measured in the superficial and deep layers of patellar cartilage using the two-pool and three-pool models in asymptomatic volunteers and patients with osteoarthritis and were compared using Wilcoxon signed rank tests. Results Within the superficial layer of patellar cartilage, FF was 22.5% and 25.6% for asymptomatic volunteers and 21.3% and 22.8% for patients with osteoarthritis when using the two-pool and three-pool models, respectively, while T2S was 73.9 msec and 62.0 msec for asymptomatic volunteers and 72.0 msec and 63.1 msec for patients with osteoarthritis when using the two-pool and three-pool models, respectively. For both asymptomatic volunteers and patients with osteoarthritis, the two-pool model provided significantly (P < 0.05) lower FF and higher T2S than the three-pool model, likely due to the effects of synovial fluid partial volume averaging. Conclusion The effects of partial volume averaging between superficial cartilage and synovial fluid may result in biased multicomponent T2 measurements that can be corrected using an mcDESPOT three-pool model containing a nonexchanging synovial fluid water pool. PMID:26435385

  7. Analysis of bacterial DNA in synovial tissue of Tunisian patients with reactive and undifferentiated arthritis by broad-range PCR, cloning and sequencing

    PubMed Central

    Siala, Mariam; Jaulhac, Benoit; Gdoura, Radhouane; Sibilia, Jean; Fourati, Hela; Younes, Mohamed; Baklouti, Sofien; Bargaoui, Naceur; Sellami, Slaheddine; Znazen, Abir; Barthel, Cathy; Collin, Elody; Hammami, Adnane; Sghir, Abdelghani

    2008-01-01

    Introduction Bacteria and/or their antigens have been implicated in the pathogenesis of reactive arthritis (ReA). Several studies have reported the presence of bacterial antigens and nucleic acids of bacteria other than those specified by diagnostic criteria for ReA in joint specimens from patients with ReA and various arthritides. The present study was conducted to detect any bacterial DNA and identify bacterial species that are present in the synovial tissue of Tunisian patients with reactive arthritis and undifferentiated arthritis (UA) using PCR, cloning and sequencing. Methods We examined synovial tissue samples from 28 patients: six patients with ReA and nine with UA, and a control group consisting of seven patients with rheumatoid arthritis and six with osteoarthritis (OA). Using broad-range bacterial PCR producing a 1,400-base-pair fragment from the 16S rRNA gene, at least 24 clones were sequenced for each synovial tissue sample. To identify the corresponding bacteria, DNA sequences were compared with sequences from the EMBL (European Molecular Biology Laboratory) database. Results Bacterial DNA was detected in 75% of the 28 synovial tissue samples. DNA from 68 various bacterial species were found in ReA and UA samples, whereas DNA from 12 bacteria were detected in control group samples. Most of the bacterial DNAs detected were from skin or intestinal bacteria. DNA from bacteria known to trigger ReA, such as Shigella flexneri and Shigella sonnei, were detected in ReA and UA samples of synovial tissue and not in control samples. DNA from various bacterial species detected in this study have not previously been found in synovial samples. Conclusion This study is the first to use broad-range PCR targeting the full 16S rRNA gene for detection of bacterial DNA in synovial tissue. We detected DNA from a wide spectrum of bacterial species, including those known to be involved in ReA and others not previously associated with ReA or related arthritis. The pathogenic

  8. The determination of inorganic sulphate in serum and synovial fluid by high performance ion chromatography.

    PubMed

    Kock, R; Schneider, H; Delvoux, B; Greiling, H

    1997-09-01

    A method for the determination of inorganic sulphate based on high performance ion chromatography is presented. The separation was performed on an anion-exchange column with a 1.8 mmol/l sodium carbonate/ 1.7 mmol/l sodium hydrogen carbonate-buffer, pH 10.35. Conductivity of the eluate was monitored after suppression of the background conductivity caused by the eluent-buffer. Serum and synovial fluid samples were prepared by ultrafiltration through membranes with a molecular mass cutoff of M(r) 10,000. The viscosity of the synovial fluids was reduced by treatment with hyaluronate lyase before ultrafiltration. The method showed a linear response for sulphate concentrations between 0.5 and 1000 mumol/l. The limit of detection was 1 mumol/l for aqueous standards. For serum the coefficient of variation within-run was 2.3%-2.4%, the coefficient of variation between days 2.9%-3.1%. For synovial fluids the coefficient of variation within-run was 3.1%-3.4%, the coefficient of variation between days 4.6%-5.7%. Standard recovery experiments performed by spiking pools of human sera containing low sulphate concentrations with sulphate concentrations between 5 mumol/l and 40 mumol/l showed recoveries between 98.9% and 100.6%. The corresponding experiments with pools of synovial fluids showed recoveries of 98.3% to 100.9%. As determined from 127 serum samples the reference range for sulphate was 262 mumol/l-420 mumol/l, with a mean value of 314 mumol/l. No dependence on age or sex was observed. The sulphate concentration in 36 synovial fluids from knees affected by inflammatory processes showed a mean value of 424 mumol/l and a standard deviation of 70 mumol/l. In 41 synovial fluids from knees affected by chronic degeneration joint disease, the sulphate concentrations were statistically significantly lower, with a mean of 374 mumol/l and a standard deviation of 58 mumol/l. The concentrations of sulphate in the synovial fluids were statistically significantly higher than those in

  9. Hyaluronic Acid (HA) Viscosupplementation on Synovial Fluid Inflammation in Knee Osteoarthritis: A Pilot Study

    PubMed Central

    Vincent, Heather K; Percival, Susan S; Conrad, Bryan P; Seay, Amanda N; Montero, Cindy; Vincent, Kevin R

    2013-01-01

    Objective: This study examined the changes in synovial fluid levels of cytokines, oxidative stress and viscosity six months after intraarticular hyaluronic acid (HA) treatment in adults and elderly adults with knee osteoarthritis (OA). Design: This was a prospective, repeated-measures study design in which patients with knee OA were administered 1% sodium hyaluronate. Patients (N=28) were stratified by age (adults, 50-64 years and elderly adults, ≥65 years). Ambulatory knee pain values and self-reported physical activity were collected at baseline and month six. Materials and Methods: Knee synovial fluid aspirates were collected at baseline and at six months. Fluid samples were analyzed for pro-inflammatory cytokines (interleukins 1β, 6,8,12, tumor necrosis factor-α, monocyte chemotactic protein), anti-inflammatory cytokines (interleukins 4, 10 13), oxidative stress (4-hydroxynonenal) and viscosity at two different physiological shear speeds 2.5Hz and 5Hz. Results: HA improved ambulatory knee pain in adults and elderly groups by month six, but adults reported less knee pain-related interference with participation in exercise than elderly adults. A greater reduction in TNF-α occurred in adults compared to elderly adults (-95.8% ± 7.1% vs 19.2% ± 83.8%, respectively; p=.044). Fluid tended to improve at both shear speeds in adults compared to the elderly adults. The reduction in pain severity correlated with the change in IL-1β levels by month six (r= -.566; p=.044). Conclusion: Reduction of knee pain might be due to improvements in synovial fluid viscosity and inflammation. Cartilage preservation may be dependent on how cytokine, oxidative stress profiles and viscosity change over time. PMID:24093052

  10. Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts

    PubMed Central

    Nielsen, Natasja; Pascal, Veronique; Fasth, Andreas E R; Sundström, Yvonne; Galsgaard, Elisabeth D; Ahern, David; Andersen, Martin; Baslund, Bo; Bartels, Else M; Bliddal, Henning; Feldmann, Marc; Malmström, Vivianne; Berg, Louise; Spee, Pieter; Söderström, Kalle

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast-like synoviocytes (FLS) are central components of the aggressive, tumour-like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory CD94/NKG2A receptor is present in RA synovial fluid. Little is known about possible cellular interactions between RA-FLS and NK cells. We used cultured RA-FLS and the human NK cell line Nishi, of which the latter expresses an NK receptor repertoire similar to that of NK cells in RA synovial fluid, as an in vitro model system of RA-FLS/NK cell cross-talk. We show that RA-FLS express numerous ligands for both activating and inhibitory NK cell receptors, and stimulate degranulation of Nishi cells. We found that NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A and its ligand HLA-E expressed on RA-FLS further enhanced Nishi cell degranulation in co-culture with RA-FLS. Using cultured RA-FLS and the human NK cell line Nishi as an in vitro model system of RA-FLS/NK cell cross-talk, our results suggest that cell-mediated cytotoxicity of RA-FLS may be one mechanism by which NK cells influence local joint inflammation in RA. PMID:24673109

  11. Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts.

    PubMed

    Nielsen, Natasja; Pascal, Veronique; Fasth, Andreas E R; Sundström, Yvonne; Galsgaard, Elisabeth D; Ahern, David; Andersen, Martin; Baslund, Bo; Bartels, Else M; Bliddal, Henning; Feldmann, Marc; Malmström, Vivianne; Berg, Louise; Spee, Pieter; Söderström, Kalle

    2014-08-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast-like synoviocytes (FLS) are central components of the aggressive, tumour-like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory CD94/NKG2A receptor is present in RA synovial fluid. Little is known about possible cellular interactions between RA-FLS and NK cells. We used cultured RA-FLS and the human NK cell line Nishi, of which the latter expresses an NK receptor repertoire similar to that of NK cells in RA synovial fluid, as an in vitro model system of RA-FLS/NK cell cross-talk. We show that RA-FLS express numerous ligands for both activating and inhibitory NK cell receptors, and stimulate degranulation of Nishi cells. We found that NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A and its ligand HLA-E expressed on RA-FLS further enhanced Nishi cell degranulation in co-culture with RA-FLS. Using cultured RA-FLS and the human NK cell line Nishi as an in vitro model system of RA-FLS/NK cell cross-talk, our results suggest that cell-mediated cytotoxicity of RA-FLS may be one mechanism by which NK cells influence local joint inflammation in RA. PMID:24673109

  12. Synovial fluid analyses detect and differentiate proteoglycan metabolism in canine experimental models of osteoarthritis and disuse atrophy.

    PubMed

    Ratcliffe, A; Beauvais, P J; Saed-Nejad, F; Shurety, W; Caterson, B

    1993-01-01

    Canine experimental models of osteoarthritis (OA) and disuse atrophy were used to study cartilage metabolism. The synovial fluids from the OA joints showed elevated levels of keratan sulfate (KS) epitope and link protein, indicating increased catabolism. Analysis of fluids from joints with disuse atrophy showed high levels of KS epitope, but no increase in link protein. Quantitation of a novel chondroitin sulfate (3B3) epitope showed it to be present only in the synovial fluids and articular cartilage of the OA joints. The results indicate that these may be important indicators, or markers, of degenerative joint disease. PMID:8456644

  13. Inhibition of HMGB1-Induced Angiogenesis by Cilostazol via SIRT1 Activation in Synovial Fibroblasts from Rheumatoid Arthritis

    PubMed Central

    Lee, Sung Won; Lee, Hye Rin; Lee, Won Suk; Rhim, Byung Yong; Hong, Ki Whan; Kim, Chi Dae

    2014-01-01

    High mobility group box chromosomal protein 1 (HMGB-1) released from injured cells plays an important role in the development of arthritis. This study investigated the anti-angiogenic effects of cilostazol in collagen-induced arthritis (CIA) of mice, and the underlying mechanisms involved. The expressions of HIF-1α, VEGF, NF-κB p65 and SIRT1 in synovial fibroblasts obtained from rheumatoid arthritis (RA) patients were assessed by Western blotting, and in vitro and in vivo angiogenesis were analyzed. Tube formations by human microvascular endothelial cells (HMVECs) were significantly increased by direct exposure to HMGB1 or to conditioned medium derived from HMGB1-stimulated RA fibroblasts, and these increases were attenuated by cilostazol, the latter of which was blocked by sirtinol. HMGB1 increased the expression of HIF-1α and VEGF and concomitantly increased nuclear NF-κB p65 and DNA binding activity, but these effects of HMGB1 were inhibited by cilostazol. SIRT1 protein expression was time-dependently decreased (3–24 hr) by HMGB1, which was recovered by pretreatment with cilostazol (1–30 µM) or resveratrol, accompanying with increased SIRT1 deacetylase activity. In the tibiotarsal joint tissues of CIA mice treated with vehicle, HIF-1α- and VEGF-positive spots and CD31 staining were markedly exaggerated, whereas SIRT1 immunofluorescence was diminished. These variables were wholly reversed in cilostazol (30 mg/kg/day)-treated mice. Furthermore, number of blood vessels stained by von Willebrand factor antibody was significantly lower in cilostazol-treated CIA mice. Summarizing, cilostazol activated SIRT1 and inhibited NF-κB-mediated transcription, thereby suppressing the expression of HIF-1α and VEGF. In addition, cilostazol caused HIF-1α deacetylation by enhancing SIRT1 activity and reduced VEGF production, thereby had an anti-angiogenic effect in vitro studies and in CIA murine model. PMID:25126750

  14. Novel Cartilage Oligomeric Matrix Protein (COMP) Neoepitopes Identified in Synovial Fluids from Patients with Joint Diseases Using Affinity Chromatography and Mass Spectrometry*

    PubMed Central

    Åhrman, Emma; Lorenzo, Pilar; Holmgren, Kristin; Grodzinsky, Alan J.; Dahlberg, Leif E.; Saxne, Tore; Heinegård, Dick; Önnerfjord, Patrik

    2014-01-01

    To identify patients at risk for progressive joint damage, there is a need for early diagnostic tools to detect molecular events leading to cartilage destruction. Isolation and characterization of distinct cartilage oligomeric matrix protein (COMP) fragments derived from cartilage and released into synovial fluid will allow discrimination between different pathological conditions and monitoring of disease progression. Early detection of disease and processes in the tissue as well as an understanding of the pathologic mechanisms will also open the way for novel treatment strategies. Disease-specific COMP fragments were isolated by affinity chromatography of synovial fluids from patients with rheumatoid arthritis, osteoarthritis, or acute trauma. Enriched COMP fragments were separated by SDS-PAGE followed by in-gel digestion and mass spectrometric identification and characterization. Using the enzymes trypsin, chymotrypsin, and Asp-N for the digestions, an extensive analysis of the enriched fragments could be accomplished. Twelve different neoepitopes were identified and characterized within the enriched COMP fragments. For one of the neoepitopes, Ser77, an inhibition ELISA was developed. This ELISA quantifies COMP fragments clearly distinguishable from total COMP. Furthermore, fragments containing the neoepitope Ser77 were released into the culture medium of cytokine (TNF-α and IL-6/soluble IL-6 receptor)-stimulated human cartilage explants. The identified neoepitopes provide a complement to the currently available commercial assays for cartilage markers. Through neoepitope assays, tools to pinpoint disease progression, evaluation methods for therapy, and means to elucidate disease mechanisms will be provided. PMID:24917676

  15. Matrix metalloproteinase-10 is a target of T and B cell responses that correlate with synovial pathology in patients with antibiotic-refractory Lyme arthritis.

    PubMed

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

    2016-05-01

    Infection-induced autoimmunity is thought to be a contributing factor in antibiotic-refractory Lyme arthritis, but studies of autoimmunity have been hindered by difficulty in identifying relevant autoantigens. We developed a novel approach that begins with the identification of T cell epitopes in synovial tissue using tandem mass spectrometry. Herein, we identified an immunogenic HLA-DR-presented peptide (T cell epitope) derived from the source protein matrix metalloproteinase-10 (MMP-10) from the synovium of a patient with antibiotic-refractory arthritis. This finding provided a bridge for the identification of autoantibody responses to MMP-10, the "first autoimmune hit" in a subgroup of patients with erythema migrans, the initial skin lesion of the infection. Months later, after priming of the immune response to MMP-10 in early infection, a subset of patients with antibiotic-responsive or antibiotic-refractory arthritis had MMP-10 autoantibodies, but only patients with antibiotic-refractory arthritis had both T and B cell responses to the protein, providing evidence for a "second autoimmune hit". Further support for a biologically relevant autoimmune event was observed by the positive correlation of anti-MMP-10 autoantibodies with distinct synovial pathology. This experience demonstrates the power of new, discovery-based methods to identify relevant autoimmune responses in chronic inflammatory forms of arthritis. PMID:26922382

  16. Norisoboldine, an alkaloid compound isolated from Radix Linderae, inhibits synovial angiogenesis in adjuvant-induced arthritis rats by moderating Notch1 pathway-related endothelial tip cell phenotype.

    PubMed

    Lu, Qian; Lu, Shuai; Gao, Xinghua; Luo, Yubin; Tong, Bei; Wei, Zhifeng; Lu, Tao; Xia, Yufeng; Chou, Guixin; Wang, Zhengtao; Dai, Yue

    2012-08-01

    Synovial angiogenesis is well recognized as participating in the pathogenesis of rheumatoid arthritis (RA) and has been regarded as a potential target for RA therapy. Previously, we have shown that norisoboldine (NOR) can protect joints from destruction in mice with collagen II-induced arthritis (CIA). Here, we investigate the effect of NOR on synovial angiogenesis in adjuvant-induced arthritis (AA) rats, and clarify the mechanisms in vitro. NOR, administered orally, significantly reduced the number of blood vessels and expression of growth factors in the synovium of AA rats. In vitro, it markedly prevented the migration and sprouting of endothelial cells. Notably, the endothelial tip cell phenotype, which is essential for the migration of endothelial cells and subsequent angiogenesis, was significantly inhibited by NOR. This inhibitory effect was attenuated by pretreatment with N-{N-[2-(3,5-difluorophenyl) acetyl]-(S)-alanyl}-(S)-phenylglycine tert-butyl ester, a Notch1 inhibitor, suggesting that the action of NOR was related to the Notch1 pathway. A molecular docking study further confirmed that NOR was able to promote Notch1 activation by binding the Notch1 transcription complex. In conclusion, NOR was able to prevent synovial angiogenesis in AA rats, which is a putatively new mechanism responsible for its anti-rheumatoid effect. The anti-angiogenesis action of NOR was likely achieved by moderating the Notch1 pathway-related endothelial tip cell phenotype with a potential action target of the Notch1 transcription complex. PMID:22875342

  17. Microscopical analysis of synovial fluid wear debris from failing CoCr hip prostheses

    NASA Astrophysics Data System (ADS)

    Ward, M. B.; Brown, A. P.; Cox, A.; Curry, A.; Denton, J.

    2010-07-01

    Metal on metal hip joint prostheses are now commonly implanted in patients with hip problems. Although hip replacements largely go ahead problem free, some complications can arise such as infection immediately after surgery and aseptic necrosis caused by vascular complications due to surgery. A recent observation that has been made at Manchester is that some Cobalt Chromium (CoCr) implants are causing chronic pain, with the source being as yet unidentified. This form of replacement failure is independent of surgeon or hospital and so some underlying body/implant interface process is thought to be the problem. When the synovial fluid from a failed joint is examined particles of metal (wear debris) can be found. Transmission Electron Microscopy (TEM) has been used to look at fixed and sectioned samples of the synovial fluid and this has identified fine (< 100 nm) metal and metal oxide particles within the fluid. TEM EDX and Electron Energy Loss Spectroscopy (EELS) have been employed to examine the composition of the particles, showing them to be chromium rich. This gives rise to concern that the failure mechanism may be associated with the debris.

  18. Limited T-cell receptor beta-chain heterogeneity among interleukin 2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis.

    PubMed Central

    Howell, M D; Diveley, J P; Lundeen, K A; Esty, A; Winters, S T; Carlo, D J; Brostoff, S W

    1991-01-01

    Rheumatoid arthritis (RA) is a disease affecting the synovial membranes of articulating joints that is thought to result from T-cell-mediated autoimmune phenomena. T cells responsible for the pathogenesis of RA are likely present in that fraction of synovial T cells that expresses the interleukin 2 receptor (IL-2R), one marker of T-cell activation. We report herein an analysis of T-cell receptor (TCR) beta-chain gene expression by IL-2R-positive synovial T cells. These T cells were isolated from uncultured synovial tissue specimens by using IL-2R-specific monoclonal antibodies and magnetic beads, and TCR beta-chain transcription was analyzed by PCR-catalyzed amplification using a panel of primers specific for the human TCR beta-chain variable region (V beta). Multiple V beta gene families were found to be transcribed in these patients samples; however, three gene families, V beta 3, V beta 14, and V beta 17, were found in a majority of the five synovial samples analyzed, suggesting that T cells bearing these V beta s had been selectively retained in the synovial microenvironment. In many instances, the V beta 3, V beta 14, or V beta 17 repertoires amplified from an individual patient were dominated by a single rearrangement, indicative of clonal expansion in the synovium and supportive of a role for these T cells in RA. Of note is a high sequence similarity between V beta 3, V beta 14, and V beta 17 polypeptides, particularly in the fourth complementarity-determining region (CDR). Given that binding sites for superantigens have been mapped to the CDR4s of TCR beta chains, the synovial localization of T cells bearing V beta s with significant CDR4 homology indicates that V beta-specific T-cell activation by superantigen may play a role in RA. PMID:1660155

  19. Statistical analysis of synovial fluid layers phase maps in the diagnostics of development and differentiation of pathological changes severity

    NASA Astrophysics Data System (ADS)

    Kvasniuk, D. I.; Vasyuk, V. L.

    2011-09-01

    A new method for differential diagnosis of pathological changes of the joints on the basis of synovial fluid was founded. Adduced description scheme and the principles of polarization filtering to determine the coordinate distributions of phase shifts.The optical model of polycrystalline networks of knee joint synovial fluid is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order) parameters are presented. They characterize the coordinate distributions of phase shifts between the orthogonal components of the amplitude in the points of laser images of synovial fluid smears and the change in optical anisotropy of this biological object. The diagnostic criteria of knee joint inflammation processes are determined.

  20. Statistical analysis of synovial fluid layers phase maps in the diagnostics of development and differentiation of pathological changes severity

    NASA Astrophysics Data System (ADS)

    Kvasniuk, D. I.; Vasyuk, V. L.

    2012-01-01

    A new method for differential diagnosis of pathological changes of the joints on the basis of synovial fluid was founded. Adduced description scheme and the principles of polarization filtering to determine the coordinate distributions of phase shifts.The optical model of polycrystalline networks of knee joint synovial fluid is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order) parameters are presented. They characterize the coordinate distributions of phase shifts between the orthogonal components of the amplitude in the points of laser images of synovial fluid smears and the change in optical anisotropy of this biological object. The diagnostic criteria of knee joint inflammation processes are determined.

  1. β1,4-galactosyltransferase-I in synovial tissue of collagen-induced rat model of rheumatoid arthritis.

    PubMed

    Wang, Hairong; Xu, Dawei; Tao, Ran; Ni, Xiaohui; Shen, Aiguo; Wang, Youhua

    2011-09-01

    β1,4-galactosyltransferase-I (β1,4-GalT-I), which is one of the best-studied glycosyltransferases, plays a key role in the synthesis of selectin ligands such as sialyl Lewis (sLe(x)) and sulfated sLe(x). Previous studies showed that inflammatory responses of β1,4-GalT-I-deficient mice were impaired because of the defect in selectin-ligand biosynthesis. However, the expression of β1,4-GalT-I and its biological function in rheumatoid arthritis (RA) remain to be elucidated. The mRNA and protein expression of β1,4-GalT-I increased in synovial tissue of the RA group compared with the Normal group at 10d and 15d after collagen-induced. Double staining indicated β1,4-GalT-I overlapped with macrophage-like synoviocytes (MLSs), fibroblast-like synoviocytes (FLSs), neutrophils and tumor necrosis factor-α (TNF-α). Moreover, β1,4-GalT-I mRNA in FLSs in vitro was affected in a dose- and time-dependent manner in response to TNF-α stimulation. ELISA revealed that expression of TNF-α was attenuated in FLSs in vitro treated with β1,4-GalT-I-Ab. We therefore suggest that β1,4-GalT-I may play an important role in the inflammation process of RA synovial tissue, which would provide the foundation for further researching into the concrete mechanism of β1,4-GalT-I in RA. PMID:21161318

  2. Bilateral Synovial Knee Chondromatosis in a Patient with Rheumatoid Arthritis: Case-report and Literature Review

    PubMed Central

    Tahmasebi, M.N; Bashti, Kaveh; Sobhan, MR; Ghorbani, GH

    2014-01-01

    We presented a female patient with RA complaining of progressive pain, swelling, and crepitation of the knee joints that was diagnosed with bilateral synovial chondromatosis (SC) of both knees. Radiographies revealed characteristic findings of SC including multiple calcified multifaceted loose bodies within both knees. Removal of cartilaginous segments as well as total synovectomy was performed arthroscopically on the left side and via open surgery on the right side. Short-term postoperative follow-up of our patient revealed improved knee function and resolution of all symptoms. PMID:25692156

  3. Bilateral Synovial Knee Chondromatosis in a Patient with Rheumatoid Arthritis: Case-report and Literature Review.

    PubMed

    Tahmasebi, M N; Bashti, Kaveh; Sobhan, Mr; Ghorbani, Gh

    2014-10-01

    We presented a female patient with RA complaining of progressive pain, swelling, and crepitation of the knee joints that was diagnosed with bilateral synovial chondromatosis (SC) of both knees. Radiographies revealed characteristic findings of SC including multiple calcified multifaceted loose bodies within both knees. Removal of cartilaginous segments as well as total synovectomy was performed arthroscopically on the left side and via open surgery on the right side. Short-term postoperative follow-up of our patient revealed improved knee function and resolution of all symptoms. PMID:25692156

  4. Phospholipase D enzymes facilitate IL-17- and TNFα-induced expression of proinflammatory genes in rheumatoid arthritis synovial fibroblasts (RASF).

    PubMed

    Friday, Sean C; Fox, David A

    2016-06-01

    In rheumatoid arthritis, the synovium exhibits fibroblast hyperplasia and dynamic infiltration of activated T cells. Interaction between rheumatoid arthritis synovial fibroblasts (RASF) and T cell subsets such as Th17 cells can stimulate RASF to express IL-6, IL-8, CCL20, and other proinflammatory mediators of joint destruction. PLD enzymes specifically cleave phosphatidyl choline (PC) producing phosphatidic acid (PA) and choline. Agonist-induced PLD activation results in PA synthesis, which is thought to be involved in a variety of rapid cellular responses such as cytokine secretion. Furthermore, the cellular response to TNF-mediated signaling in myeloid cells is in part mediated by PLD1. However, very few studies have examined the role of PLD enzymes in pro-inflammatory responses of RASF to key pathogenic cytokines such as TNF and IL-17. Microarray analysis of RASF showed that phospholipase D1 (PLD1) is among genes significantly induced by IL-17. We therefore hypothesized that PLD1 might have a role in RASF responses to proinflammatory cytokines. We used 1-butanol, PLD1-specific siRNAs, and small molecule inhibitors specific for PLD1 or PLD2, to investigate the possible role of PLD enzymes in basal, IL-17-, and/or TNFα-evoked expression of proinflammatory cytokines and chemokines by RASF. We studied the in vitro responses of RASF to IL-17A and/or TNFα, with particular attention to effects on IL-6, IL-8 and CCL20 mRNA and secretion as determined by RT-QPCR and ELISA, respectively. Transcriptional and prominent post-transcriptional effects were demonstrated, with robust decreases in RASF secretion of IL-6, IL-8, and CCL20 when both PLD isoforms were inhibited together. Moreover, RA synovial biopsy explants cultured in media containing PLD isoform-specific inhibitors showed significantly reduced constitutive secretion of IL-6 and IL-8. PLD enzymes could be promising targets for controlling proinflammatory gene expression in the treatment of RA in view of roles for

  5. Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibroblasts

    PubMed Central

    Ruedel, Anke; Dietrich, Peter; Schubert, Thomas; Hofmeister, Simone; Hellerbrand, Claus; Bosserhoff, Anja-Katrin

    2015-01-01

    Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real-time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine-1β lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3’UTR binding site for miR-188-5p. COL1A1and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188-5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA. PMID:26191188

  6. Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibroblasts

    PubMed Central

    Ruedel, Anke; Dietrich, Peter; Schubert, Thomas; Hofmeister, Simone; Hellerbrand, Claus; Bosserhoff, Anja Katrin

    2015-01-01

    Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real-time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine-1β lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3’UTR binding site for miR-188-5p. COL1A1 and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188-5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA. PMID:26261542

  7. Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibroblasts.

    PubMed

    Ruedel, Anke; Dietrich, Peter; Schubert, Thomas; Hofmeister, Simone; Hellerbrand, Claus; Bosserhoff, Anja-Katrin

    2015-01-01

    Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real-time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine-1β lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3'UTR binding site for miR-188-5p. COL1A1and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188-5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA. PMID:26191188

  8. Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibroblasts.

    PubMed

    Ruedel, Anke; Dietrich, Peter; Schubert, Thomas; Hofmeister, Simone; Hellerbrand, Claus; Bosserhoff, Anja Katrin

    2015-01-01

    Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real-time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine-1β lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3'UTR binding site for miR-188-5p. COL1A1 and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188-5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA. PMID:26261542

  9. Correlation and fractional analysis of synovial fluid microscopic images for diagnostics and differentiation of pathological conditions in joints

    NASA Astrophysics Data System (ADS)

    Kvasniuk, D. I.; Vasyuk, V. L.

    2011-09-01

    In this paper, was given the basis of the method of spectral Stokes polarimetry of human synovial fluid. The optical model of polycrystalline networks of human knee joint synovial fluid is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order), correlation (correlation area, asymmetry coefficient and autocorrelation function excess) and fractal (dispersion of logarithmic dependencies of power spectra) parameters are presented. They characterize spectral distributions of polarization azimuth and ellipticity of the body's electromagnetic radiation and dynamics of change in optical anisotropy of this biological object. The diagnostic criteria of human knee joint inflammation processes are determined.

  10. Correlation and fractional analysis of synovial fluid microscopic images for diagnostics and differentiation of pathological conditions in joints

    NASA Astrophysics Data System (ADS)

    Kvasniuk, D. I.; Vasyuk, V. L.

    2012-01-01

    In this paper, was given the basis of the method of spectral Stokes polarimetry of human synovial fluid. The optical model of polycrystalline networks of human knee joint synovial fluid is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order), correlation (correlation area, asymmetry coefficient and autocorrelation function excess) and fractal (dispersion of logarithmic dependencies of power spectra) parameters are presented. They characterize spectral distributions of polarization azimuth and ellipticity of the body's electromagnetic radiation and dynamics of change in optical anisotropy of this biological object. The diagnostic criteria of human knee joint inflammation processes are determined.

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

    PubMed Central

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

    2016-01-01

    Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP) cells in equine synovial fluid (SF) and to determine the effect of fibroblast growth factor 2 (FGF-2) on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU) assays were performed during primary cultures. At first passage, SF-cells were seeded at low density, with or without FGF-2. Following monolayer expansion and serial immunophenotyping, cells were transferred to chondrogenic pellet cultures. Pellets were analyzed for chondrogenic mRNA expression and cartilage matrix secretion. There was a mean of 59.2 CFU/mL of SF. FGF-2 increased the number of population doublings during two monolayer passages and halved the population doubling times. FGF-2 did not alter the immunophenotype of SF-CPs during monolayer expansion, nor did FGF-2 compromise chondrogenesis. Hypertrophic phenotypic markers were not expressed in control or FGF-2 groups. FGF-2 did prevent the development of a “fibroblastic” cell layer around pellet periphery. FGF-2 significantly accelerates in vitro SF-CP expansion, the major hurdle to clinical application of this cell population, without detrimentally affecting subsequent chondrogenic capacity. PMID:26839571

  12. Fluorescent sensing of pyrophosphate anion in synovial fluid based on DNA-attached magnetic nanoparticles.

    PubMed

    Tong, Li-Li; Chen, Zhen-zhen; Jiang, Zhong-yao; Sun, Miao-miao; Li, Lu; Liu, Ju; Tang, Bo

    2015-10-15

    In this work, a new fluorescent method for sensitive detection of pyrophosphate anion (P2O7(4-), PPi) in the synovial fluid was developed using fluorophore labeled single-stranded DNA-attached Fe3O4 NPs. The sensing approach is based on the strong affinity of PPi to Fe3O4 NPs and highly efficient fluorescent quenching ability of Fe3O4 NPs for fluorophore labeled single-stranded DNA. In the presence of PPi, the fluorescence would enhance dramatically due to desorption of fluorophore labeled single-stranded DNA from the surface of Fe3O4 NPs, which allowed the analysis of PPi in a very simple manner. The proposed sensing system allows for the sensitive determination of PPi in the range of 2.0 × 10(-7)-4 × 10(-6)M with a detection limit of 76 nM. Importantly, the protocol exhibits excellent selectivity for the determination of PPi over other phosphate-containing compounds. The method was successfully applied to the determination of PPi in the synovial fluid, which suggests our proposed method has great potential for diagnostic purposes. PMID:25957830

  13. Determination of marbofloxacin in plasma and synovial fluid by ultrafiltration followed by HPLC-MS/MS.

    PubMed

    Montesano, Camilla; Curini, Roberta; Sergi, Manuel; Compagnone, Dario; Celani, Gianluca; Varasano, Vincenzo; Petrizzi, Lucio; Amorena, Michele

    2016-05-10

    A rapid LC-MS/MS method for the determination of marbofloxacin in plasma and synovial fluid is presented in this study. The method uses a rapid sample preparation which only requires an ultrafiltration step with centrifugal filter devices. The optimized procedure allows a minimal need of sample (175μL), particularly useful for synovial fluid samples which amount is rather limited; it is simple, rapid and easily applicable providing anyhow a satisfactory clean up, demonstrated by post-infusion experiments. On the other hand to maximize the speed of the analysis an ultrafast chromatographic separation has been obtained by selecting a column of 20mm; the reduced run-time is suitable for processing numerous samples on a daily basis. Linearity was assessed in the range 5-2500ngmL(-1); ofloxacin was used as internal standard. LOD and LOQ were respectively 1 and 5ng/mL. The method was successfully applied to a set of samples generated during an experimental veterinary study. PMID:26859613

  14. Effects of ACL Reconstructive Surgery on Temporal Variations of Cytokine Levels in Synovial Fluid

    PubMed Central

    Bigoni, Marco; Gandolla, Marta; Sacerdote, Paola; Piatti, Massimiliano; Castelnuovo, Alberto; Franchi, Silvia; Gorla, Massimo; Munegato, Daniele; Gaddi, Diego; Pedrocchi, Alessandra; Omeljaniuk, Robert J.; Locatelli, Vittorio; Torsello, Antonio

    2016-01-01

    Anterior cruciate ligament (ACL) reconstruction restores knee stability but does not reduce the incidence of posttraumatic osteoarthritis induced by inflammatory cytokines. The aim of this research was to longitudinally measure IL-1β, IL-6, IL-8, IL-10, and TNF-α levels in patients subjected to ACL reconstruction using bone-patellar tendon-bone graft. Synovial fluid was collected within 24–72 hours of ACL rupture (acute), 1 month after injury immediately prior to surgery (presurgery), and 1 month thereafter (postsurgery). For comparison, a “control” group consisted of individuals presenting chronic ACL tears. Our results indicate that levels of IL-6, IL-8, and IL-10 vary significantly over time in reconstruction patients. In the acute phase, the levels of these cytokines in reconstruction patients were significantly greater than those in controls. In the presurgery phase, cytokine levels in reconstruction patients were reduced and comparable with those in controls. Finally, cytokine levels increased again with respect to control group in the postsurgery phase. The levels of IL-1β and TNF-α showed no temporal variation. Our data show that the history of an ACL injury, including trauma and reconstruction, has a significant impact on levels of IL-6, IL-8, and IL-10 in synovial fluid but does not affect levels of TNF-α and IL-1β. PMID:27313403

  15. Biodynamic Performance of Hyaluronic Acid versus Synovial fluid of the Knee for Osteoarthritic Therapy

    PubMed Central

    Corvelli, Michael; Che, Bernadette; Saeui, Christopher; Singh, Anirudha; Elisseeff, Jennifer

    2015-01-01

    Hyaluronic acid (HA), a natural biomaterial present in healthy joints but depleted in osteoarthritis (OA), has been employed clinically to provide symptomatic relief of joint pain. Joint movement combined with a reduced joint lubrication in osteoarthritic knees can result in increased wear and tear, chondrocyte apoptosis, and inflammation, leading to cascading cartilage deterioration. Therefore, development of an appropriate cartilage model and evaluation for its friction properties with potential lubricants in different conditions is necessary, which can closely resemble a mechanically induced OA cartilage. Additionally, the comparison of different models with and without endogenous lubricating surface zone proteins, such as PRG4 promotes a well-rounded understanding of cartilage lubrication. In this study, we present our findings on the lubricating effects of HA on different articular cartilage model surfaces in comparison to synovial fluid, a physiological lubricating biomaterial. The mechanical testings data demonstrated that HA reduced average static and kinetic friction coefficient values of the cartilage samples by 75% and 70%, respectively. Furthermore, HA mimicked the friction characteristics of freshly harvested natural synovial fluid throughout all tested and modeled OA conditions with no statistically significant difference. These characteristics led us to exclusively identify HA as an effective boundary layer lubricant in the technology that we develop to treat OA [Singh et al. 2104]. PMID:25858258

  16. Biodynamic performance of hyaluronic acid versus synovial fluid of the knee in osteoarthritis.

    PubMed

    Corvelli, Michael; Che, Bernadette; Saeui, Christopher; Singh, Anirudha; Elisseeff, Jennifer

    2015-08-01

    Hyaluronic acid (HA), a natural biomaterial present in healthy joints but depleted in osteoarthritis (OA), has been employed clinically to provide symptomatic relief of joint pain. Joint movement combined with a reduced joint lubrication in osteoarthritic knees can result in increased wear and tear, chondrocyte apoptosis, and inflammation, leading to cascading cartilage deterioration. Therefore, development of an appropriate cartilage model that can be evaluated for its friction properties with potential lubricants in different conditions is necessary, which can closely resemble a mechanically induced OA cartilage. Additionally, a comparison of different models with and without endogenous lubricating surface zone proteins, such as PRG4 promotes a well-rounded understanding of cartilage lubrication. In this study, we present our findings on the lubricating effects of HA on different articular cartilage model surfaces in comparison to synovial fluid, a physiological lubricating biomaterial. The mechanical testings data demonstrated that HA reduced average static and kinetic friction coefficient values of the cartilage samples by 75% and 70%, respectively. Furthermore, HA mimicked the friction characteristics of freshly harvested natural synovial fluid throughout all tested and modeled OA conditions with no statistically significant difference. These characteristics led us to exclusively identify HA as an effective boundary layer lubricant in the technology that we develop to treat OA (Singh et al., 2014). PMID:25858258

  17. Evaluation of a Genus- and Group-Specific Rapid PCR Assay Panel on Synovial Fluid for Diagnosis of Prosthetic Knee Infection

    PubMed Central

    Melendez, Dante P.; Greenwood-Quaintance, Kerryl E.; Berbari, Elie F.; Osmon, Douglas R.; Mandrekar, Jayawant N.; Hanssen, Arlen D.

    2015-01-01

    We evaluated a genus- and group-specific PCR assay panel using 284 prosthetic knee synovial fluid samples collected from patients presenting to our institution with implant failure. Using the Musculoskeletal Infection Society diagnostic criteria, 88 and 196 samples were classified as showing prosthetic joint infection (PJI) and aseptic failure (AF), respectively. Sensitivities of the synovial fluid PCR panel and culture were 55.6% and 76.1% (P ≤ 0.001), respectively, and specificities were 91.8% and 97.4% (P = 0.016), respectively. Among the 70 subjects who had received antibiotics within the month preceding synovial fluid aspiration (48 of whom had PJI), PCR panel and synovial fluid culture sensitivities were 64.5% and 85.4%, respectively (P < 0.0001). In this group, the PCR panel detected Staphylococcus aureus in two culture-negative PJI cases. Overall, the evaluated molecular diagnostic tool had low sensitivity when applied to synovial fluid. PMID:26537446

  18. [Synovial lipoma arborescens].

    PubMed

    Semenova, L A; Radenska-Lopovok, S G; Khaplinin, A P; Malakhova, S O

    2014-01-01

    The paper describes a case of synovial lipoma arborescens (tree-forming lipoma) of the knee joint. This tumor is a variety of lipomas--a benign tumor composed of mature adipose tissue without signs of atypia. Most investigators regard lipoma as a reactive rather than neoplastic process. X-ray and histological studies should be performed for its differential diagnosis with pigmented villonodular synovitis, synovial chondromatosis, synovial hemangioma, xanthoma, a group of chronic synovitis in rheumatic diseases (rheumatoid arthritis, amyloid arthropathy, psoriatic arthritis). Its final diagnosis is possible only after morphological study. PMID:25306627

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

    PubMed Central

    Selvi, E; Manganelli, S; Catenaccio, M; De Stefano, R; Frati, E; Cucini, S; Marcolongo, R

    2001-01-01

    OBJECTIVE—To evaluate whether the Diff Quik (DQ) staining method might prove useful in identifying monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals on permanent mounted stained slides.
METHODS—27 synovial fluid (SF) samples obtained from the knees of 21 patients with acute CPPD disease and 6 with acute gout were studied. Wet analysis for crystal detection and identification was performed within one hour of joint aspiration. In addition, 16 inflammatory synovial effusions obtained from patients with knee arthritis induced by non-crystalline inflammatory diseases were studied. For each SF, a DQ stained slide was analysed by two of the authors trained in SF analysis. The observers were blinded to the type of crystals present in the SF. Each slide was analysed by compensated polarised as well as transmitted light microscopy. An SF was considered positive if intracellular and/or extracellular crystals were clearly identified. In addition, the observer was asked to identify the type of the crystals using compensated polarised light microscopy. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the DQ staining method were determined.
RESULTS—51 true positive and 28 true negative cases were correctly classified (39 CPPD samples, 12 MSU samples, 28 samples of crystal unrelated arthropathies). Overall, four false positive and three false negative cases were reported. In all the false positive cases, extracellular CPPD crystals were erroneously identified, whereas CPPD crystals present in the SF were not identified in the three false negative cases. All MSU specimens were correctly diagnosed. The overall specificity, sensitivity, and accuracy using DQ stained slides for crystal confirmation were respectively 87.5%, 94.4%, and 91.9%. The PPV was 92.7% and the NPV 90.3%. In particular, the specificity, sensitivity, and accuracy for CPPD detection were 90.9%, 92.9%, and 91

  20. Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses

    PubMed Central

    Hunter, Barbara G.; Larson, Maureen K.

    2015-01-01

    Anecdotal accounts of tiludronate administration via intravenous regional limb perfusion (IVRLP) exist despite a lack of information regarding safety for synovial structures in the perfused area. The objective of this study was to determine whether tiludronate concentrations in synovial structures after IVRLP with low dose (0.5 mg, LDT) or high dose (50 mg, HDT) tiludronate remain below a value demonstrated in vitro to be safe for articular cartilage (<19,000 ng/ml), and to determine effects of tiludronate on synovial fluid cytology variables compared to saline perfused control limbs. Using a randomized controlled experimental study design, horses received IVRLP with LDT (n = 6) or HDT (n = 6) in one forelimb and IVRLP with saline in the contralateral limb. Synovial fluid cytology variables and tiludronate concentrations were evaluated in navicular bursae (NB), and distal interphalangeal (DIP) and metacarpophalangeal (MCP) joints one week before and 30–45 min after IVRLP, and in DIP and MCP joints 24 h after IVRLP. Data were analyzed with 2-way rmANOVA (p < 0.05). Highest measured synovial fluid tiludronate concentrations occurred 30–45 min post-perfusion. Mean tiludronate concentrations were lower in LDT limbs (MCP = 39.6 ± 14.3 ng/ml, DIP = 118.1 ± 66.6 ng/ml, NB = 82.1 ± 30.2 ng/ml) than in HDT limbs (MCP = 3,745.1 ± 1,536.6 ng/ml, DIP = 16,274.0 ± 5,460.2 ng/ml, NB = 6,049.3 ± 1,931.7 ng/ml). Tiludronate concentration was >19,000 ng/ml in DIP joints of two HDT limbs. Tiludronate was measurable only in synovial fluid from HDT limbs 24 h post-perfusion. There were no differences in synovial fluid cytology variables between control and treated limbs. Conclusions. In some horses, IVRLP with HDT may result in synovial fluid concentrations of tiludronate that may have adverse effects on articular cartilage, based on in vitro data. IVRLP with LDT is unlikely to promote articular cartilage degradation. Further studies to determine a safe and effective dose

  1. The tumour-associated glycoprotein podoplanin is expressed in fibroblast-like synoviocytes of the hyperplastic synovial lining layer in rheumatoid arthritis

    PubMed Central

    2011-01-01

    Introduction Activated fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) share many characteristics with tumour cells and are key mediators of synovial tissue transformation and joint destruction. The glycoprotein podoplanin is upregulated in the invasive front of several human cancers and has been associated with epithelial-mesenchymal transition, increased cell migration and tissue invasion. The aim of this study was to investigate whether podoplanin is expressed in areas of synovial transformation in RA and especially in promigratory RA-FLS. Methods Podoplanin expression in human synovial tissue from 18 RA patients and nine osteoarthritis (OA) patients was assessed by immunohistochemistry and confirmed by Western blot analysis. The expression was related to markers of synoviocytes and myofibroblasts detected by using confocal immunofluoresence microscopy. Expression of podoplanin, with or without the addition of proinflammatory cytokines and growth factors, in primary human FLS was evaluated by using flow cytometry. Results Podoplanin was highly expressed in cadherin-11-positive cells throughout the synovial lining layer in RA. The expression was most pronounced in areas with lining layer hyperplasia and high matrix metalloproteinase 9 expression, where it coincided with upregulation of α-smooth muscle actin (α-sma). The synovium in OA was predominantly podoplanin-negative. Podoplanin was expressed in 50% of cultured primary FLSs, and the expression was increased by interleukin 1β, tumour necrosis factor α and transforming growth factor β receptor 1. Conclusions Here we show that podoplanin is highly expressed in FLSs of the invading synovial tissue in RA. The concomitant upregulation of α-sma and podoplanin in a subpopulation of FLSs indicates a myofibroblast phenotype. Proinflammatory mediators increased the podoplanin expression in cultured RA-FLS. We conclude that podoplanin might be involved in the synovial tissue transformation and

  2. Relationship between automated total nucleated cell count and enumeration of cells on direct smears of canine synovial fluid

    PubMed Central

    Dusick, Allison; Young, Karen M.; Muir, Peter

    2016-01-01

    Canine osteoarthritis is a common condition seen in veterinary clinical practice and causes considerable morbidity in dogs as they age. Synovial fluid analysis is an important tool for diagnosis and treatment of canine joint disease and obtaining a total nucleated cell count (TNCC) is particularly important. The low volume of fluid obtained during arthrocentesis is often insufficient for obtaining an automated TNCC, thereby limiting sample interpretation. The aim of the present study was to investigate whether estimation of TNCC in canine synovial fluid could be achieved by performing manual cell counts on direct smears of fluid. Fifty eight synovial fluid samples, taken by arthrocentesis from 48 dogs, were included in the study. Direct smears of synovial fluid were prepared, and hyaluronidase added before cell counts were obtained using a commercial laser-based instrument. A protocol was established to count nucleated cells in a specific region of the smear, using a serpentine counting pattern; mean number of nucleated cells/400× field was then calculated. There was a positive correlation between the automated TNCC and mean manual cell count, with more variability at higher TNCC. Regression analysis was performed to estimate TNCC from manual counts. By this method, 78% of the samples were correctly predicted to fall into one of three categories (within the reference interval, mildly to moderately elevated, or markedly elevated) relative to the automated TNCC. Intra-observer and inter-observer agreement was good to excellent. The results of the study suggest that interpretation of canine synovial fluid samples of low volume can be aided by manual cell counting of direct smears. PMID:25439439

  3. A Systems Biology Approach to Synovial Joint Lubrication in Health, Injury, and Disease

    PubMed Central

    Hui, Alexander Y.; McCarty, William J.; Masuda, Koichi; Firestein, Gary S.; Sah, Robert L.

    2013-01-01

    The synovial joint contains synovial fluid (SF) within a cavity bounded by articular cartilage and synovium. SF is a viscous fluid that has lubrication, metabolic, and regulatory functions within synovial joints. SF contains lubricant molecules, including proteoglycan-4 and hyaluronan. SF is an ultrafiltrate of plasma with secreted contributions from cell populations lining and within the synovial joint space, including chondrocytes and synoviocytes. Maintenance of normal SF lubricant composition and function are important for joint homeostasis. In osteoarthritis, rheumatoid arthritis, and joint injury, changes in lubricant composition and function accompany alterations in the cytokine and growth factor environment and increased fluid and molecular transport through joint tissues. Thus, understanding the synovial joint lubrication system requires a multi-faceted study of the various parts of the synovial joint and their interactions. Systems biology approaches at multiple scales are being used to describe the molecular, cellular, and tissue components and their interactions that comprise the functioning synovial joint. Analyses of the transcriptome and proteome of SF, cartilage, and synovium suggest that particular molecules and pathways play important roles in joint homeostasis and disease. Such information may be integrated with physicochemical tissue descriptions to construct integrative models of the synovial joint that ultimately may explain maintenance of health, recovery from injury, or development and progression of arthritis. PMID:21826801

  4. Chlamydial infection preceding the development of rheumatoid arthritis: a brief report.

    PubMed

    Jolly, Meenakshi; Curran, J J

    2004-10-01

    Chlamydia trachomatis-triggered reactive arthritis is a well-documented entity that has been extensively described. We do not have a clear understanding about the inflammatory oligoarthritis associated with the presence of this organism. It is rarely cultured from the synovial fluid, but is usually detectable by molecular biological techniques. Typically, Chlamydia trachomatis causes a sterile but inflammatory oligoarthritis. We report an unusual case of inflammatory monoarthritis in a young woman in whom Chlamydia was isolated from the synovial fluid. This is the first case of documented isolation of Chlamydia from synovial fluid, which subsequently was diagnosed as rheumatoid arthritis. PMID:15459816

  5. Relationship between automated total nucleated cell count and enumeration of cells on direct smears of canine synovial fluid.

    PubMed

    Dusick, Allison; Young, Karen M; Muir, Peter

    2014-12-01

    Canine osteoarthritis is a common disorder seen in veterinary clinical practice and causes considerable morbidity in dogs as they age. Synovial fluid analysis is an important tool for diagnosis and treatment of canine joint disease and obtaining a total nucleated cell count (TNCC) is particularly important. However, the low sample volumes obtained during arthrocentesis are often insufficient for performing an automated TNCC, thereby limiting diagnostic interpretation. The aim of the present study was to investigate whether estimation of TNCC in canine synovial fluid could be achieved by performing manual cell counts on direct smears of fluid. Fifty-eight synovial fluid samples, taken by arthrocentesis from 48 dogs, were included in the study. Direct smears of synovial fluid were prepared, and hyaluronidase added before cell counts were obtained using a commercial laser-based instrument. A protocol was established to count nucleated cells in a specific region of the smear, using a serpentine counting pattern; the mean number of nucleated cells per 400 × field was then calculated. There was a positive correlation between the automated TNCC and mean manual cell count, with more variability at higher TNCC. Regression analysis was performed to estimate TNCC from manual counts. By this method, 78% of the samples were correctly predicted to fall into one of three categories (within the reference interval, mildly to moderately increased, or markedly increased) relative to the automated TNCC. Intra-observer and inter-observer agreement was good to excellent. The results of the study suggest that interpretation of canine synovial fluid samples of low volume can be aided by methodical manual counting of cells on direct smears. PMID:25439439

  6. Single Molecule Microscopy Reveals an Increased Hyaluronan Diffusion Rate in Synovial Fluid from Knees Affected by Osteoarthritis

    PubMed Central

    Kohlhof, Hendrik; Gravius, Sascha; Kohl, Sandro; Ahmad, Sufian S.; Randau, Thomas; Schmolders, Jan; Rommelspacher, Yorck; Friedrich, Max; Kaminski, Tim P.

    2016-01-01

    Osteoarthritis is a common and progressive joint disorder. Despite its widespread, in clinical practice only late phases of osteoarthritis that are characterized by severe joint damage are routinely detected. Since osteoarthritis cannot be cured but relatively well managed, an early diagnosis and thereby early onset of disease management would lower the burden of osteoarthritis. Here we evaluated if biophysical parameters of small synovial fluid samples extracted by single molecule microscopy can be linked to joint damage. In healthy synovial fluid (ICRS-score < 1) hyaluronan showed a slower diffusion (2.2 μm2/s, N = 5) than in samples from patients with joint damage (ICRS-score > 2) (4.5 μm2/s, N = 16). More strikingly, the diffusion coefficient of hyaluronan in healthy synovial fluid was on average 30% slower than expected by sample viscosity. This effect was diminished or missing in samples from patients with joint damage. Since single molecule microscopy needs only microliters of synovial fluid to extract the viscosity and the specific diffusion coefficient of hyaluronan this method could be of use as diagnostic tool for osteoarthritis. PMID:26868769

  7. Isolation and characterization of rheumatoid arthritis synovial fibroblasts from primary culture — primary culture cells markedly differ from fourth-passage cells

    PubMed Central

    Zimmermann, Thomas; Kunisch, Elke; Pfeiffer, Robert; Hirth, Astrid; Stahl, Hans-Detlev; Sack, Ulrich; Laube, Anke; Liesaus, Eckehard; Roth, Andreas; Palombo-Kinne, Ernesta; Emmrich, Frank; Kinne, Raimund W

    2001-01-01

    To reduce culture artifacts by conventional repeated passaging and long-term culture in vitro, the isolation of synovial fibroblasts (SFB) was attempted from rheumatoid arthritis (RA) synovial membranes by trypsin/collagenase digest, short-term in vitro adherence (7 days), and negative isolation using magnetobead-coupled anti-CD14 monoclonal antibodies. This method yielded highly enriched SFB (85% prolyl-4-hydroxylase+/74% Thy-1/CD90+ cells; <2% contaminating macrophages; <1% leukocytes/endothelial cells) that, in comparison with conventional fourth-passage RA-SFB, showed a markedly different phenotype and significantly lower proliferation rates upon stimulation with platelet-derived growth factor and IL-1β. This isolation method is simple and reliable, and may yield cells with features closer to the in vivo configuration of RA-SFB by avoiding extended in vitro culture. PMID:11178129

  8. Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses.

    PubMed

    Knych, H K; Harrison, L M; Casbeer, H C; McKemie, D S

    2014-04-01

    Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time-related urine and synovial fluid concentrations following intra-articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra-articular administration of MPA (100 mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77 days postdrug administration and analyzed using tandem liquid chromatography-mass spectrometry (LC-MS/MS). Maximum measured plasma MPA concentrations were 6.06 ± 1.57 at 0.271 days (6.5 h; range: 5.0-7.92 h) and 6.27 ± 1.29 ng/mL at 0.276 days (6.6 h; range: 4.03-12.0 h) for horses that had synovial fluid collected (group 1) and those that did not (group 2), respectively. The plasma terminal half-life was 1.33 ± 0.80 and 0.843 ± 0.414 days for groups 1 and 2, respectively. MPA was undetectable by day 6.25 ± 2.12 (group 1) and 4.81 ± 2.56 (group 2) in plasma and day 17 (group 1) and 14 (group 2) in urine. MPA concentrations in synovial fluid remained above the limit of detection (LOD) for up to 77 days following intra-articular administration, suggesting that plasma and urine concentrations are not a good indicator of synovial fluid concentrations. PMID:23876165

  9. Contributions of the lymphatic and microvascular systems to fluid absorption from the synovial cavity of the rabbit knee.

    PubMed

    Levick, J R

    1980-09-01

    1. The trans-synovial flow (Qs) of Ringer solution from the cavity of immobile knee (stifle) joints was determined in anaesthetized rabbits when intra-articular hydrostatic pressure (PJ) was elevated in steps from 2 to 25 cm H2O. 2. It has been demonstrated previously (Levick, 1978) that slope DQs/dPJ shows an abrupt sixfold increase at a 'breaking point' (PB) around 9 . 5 cm H2O, rising from a mean of 0 . 49 microliter.min-1 cm H2O-1 (PJ less than PB) to 2 . 81 microliter.min-1 cm H2O-1 (PJ greater than PB). 3. Perforation of the synovial intima by an intra-articular cannula increased dQs/dPJ below breaking pressure and thus largely abolished the breaking point phenomenon, indicating that the phenomenon might be simulated by a break-down in synovial resistance to flow. 4. Ligation of the femoral lymph trunks draining the joint did not significantly alter the relationship between Qs and PJ. The slope dQs/dPJ was 0 . 60 +/- 0 . 17 microliter.min-1 cm H2O-1 (mean +/- S.E.) below a breaking pressure of 8 . 8--10.5 cm H2O, and 2 . 90 +/- 0 . 64 microliter.min-1 cm H2O-1 above breaking pressure. Thus changes in synovial lymph flow did not explain the breaking point phenomenon. 5. Interruption of synovial blood flow by vascular clamps or by killing the animal reduced, but did not abolish fluid absorption; nor was the breaking point phenomenon abolished. Slope dQs/dPJ increased from 0 . 37 +/- 0 . 06 microliter.min-1 cm H2O-1 below breaking point (10 . 5 +/- 1 . 0 cm H2O) to between 1 . 82 and 0 . 96 +/- 0 . 15 microliter.min-1 cm H2O-1 above breaking pressure. Fluid accumulated in extra-synovial interstitial spaces. 6. When the synovial intima was divested of its surrounding tissues, lymphatic and vascular supplies by extensive dissection, the denuded synovium still showed a marked increase in hydraulic conductivity at normal breaking pressures. The breaking point phenomenon was therefore not caused by changes in extra-synovial interstitial pressure or compliance. 7. It

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

    SciTech Connect

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

    1989-01-01

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

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

    PubMed

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

    2015-01-01

    Septic arthritis/tenosynovitis in the horse can have life-threatening consequences. The purpose of this cross-sectional retrospective study was to describe ultrasound characteristics of septic arthritis/tenosynovitis in a group of horses. Diagnosis of septic arthritis/tenosynovitis was based on historical and clinical findings as well as the results of the synovial fluid analysis and/or positive synovial culture. Ultrasonographic findings recorded were degree of joint/sheath effusion, degree of synovial membrane thickening, echogenicity of the synovial fluid, and presence of hyperechogenic spots and fibrinous loculations. Ultrasonographic findings were tested for dependence on the cause of sepsis, time between admission and beginning of clinical signs, and the white blood cell counts in the synovial fluid. Thirty-eight horses with confirmed septic arthritis/tenosynovitis of 43 joints/sheaths were included. Degree of effusion was marked in 81.4% of cases, mild in 16.3%, and absent in 2.3%. Synovial thickening was mild in 30.9% of cases and moderate/severe in 69.1%. Synovial fluid was anechogenic in 45.2% of cases and echogenic in 54.8%. Hyperechogenic spots were identified in 32.5% of structures and fibrinous loculations in 64.3%. Relationships between the degree of synovial effusion, degree of the synovial thickening, presence of fibrinous loculations, and the time between admission and beginning of clinical signs were identified, as well as between the presence of fibrinous loculations and the cause of sepsis (P ≤ 0.05). Findings indicated that ultrasonographic findings of septic arthritis/tenosynovitis may vary in horses, and may be influenced by time between admission and beginning of clinical signs. PMID:25046562

  12. Legg-Calvé-Perthes disease produces chronic hip synovitis and elevation of interleukin-6 in the synovial fluid.

    PubMed

    Kamiya, Nobuhiro; Yamaguchi, Ryosuke; Adapala, Naga Suresh; Chen, Elena; Neal, David; Jack, Obrien; Thoveson, Alec; Gudmundsson, Paul; Brabham, Case; Aruwajoye, Olumide; Drissi, Hicham; Kim, Harry K W

    2015-06-01

    Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder of ischemic osteonecrosis of the femoral head. Hip joint synovitis is a common feature of LCPD, but the nature and pathophysiology of the synovitis remain unknown. The purpose of this study was to determine the chronicity of the synovitis and the inflammatory cytokines present in the synovial fluid at an active stage of LCPD. Serial MRI was performed on 28 patients. T2-weighted and gadolinium-enhanced MR images were used to assess synovial effusion and synovial enhancement (hyperemia) over time. A multiple-cytokine assay was used to determine the levels of 27 inflammatory cytokines and related factors present in the synovial fluid from 13 patients. MRI analysis showed fold increases of 5.0 ± 3.3 and 3.1 ± 2.1 in the synovial fluid volume in the affected hip compared to the unaffected hip at the initial and the last follow-up MRI, respectively. The mean duration between the initial and the last MRI was 17.7 ± 8.3 months. The volume of enhanced synovium on the contrast MRI was increased 16.5 ± 8.5 fold and 6.3 ± 5.6 fold in the affected hip compared to the unaffected hip at the initial MRI and the last follow-up MRI, respectively. In the synovial fluid of the affected hips, IL-6 protein levels were significantly increased (LCPD: 509 ± 519 pg/mL, non-LCPD: 19 ± 22 pg/mL; p = 0.0005) on the multi-cytokine assay. Interestingly, IL-1β and TNF-α levels were not elevated. In the active stage of LCPD, chronic hip synovitis and significant elevation of IL-6 are produced in the synovial fluid. Further studies are warranted to investigate the role of IL-6 on the pathophysiology of synovitis in LCPD and how it affects bone healing. PMID:25556551

  13. Cytokine expression and synovial pathology in the initiation and spontaneous resolution phases of adjuvant arthritis: Interleukin-17 expression is upregulated in early disease

    PubMed Central

    Bush, K A; Walker, J S; Lee, C S; Kirkham, B W

    2001-01-01

    The aim of this study was to understand the immune processes controlling the initiation and spontaneous resolution of adjuvant arthritis (AA). We investigated synovial T-cell recruitment and mRNA expression of IL-17 and other important disease related cytokines, IFN-γ, IL-2, IL-4, TNF and TGF-β in inguinal lymph node (ILN) and synovial membrane (SM). Arthritis severity was assessed by a numerical rating score and rats were sacrificed every 3–4 days postadjuvant induction. Further assessment involved quantitative radiology and histology of the ankle joints on each day, and the ILN and SM were removed for RNA extraction. Cytokine mRNA expression was measured using RT-PCR and densitometry. Paraffin sections of rat ankle joints were stained for T-cells (CD3) by immunohistochemistry. In the ILN, there was an increase in IL-17, TNF and IFN-γ expression in the early stages of disease, with a secondary sustained increase in IFN-γ expression. In the SM, there was expression of T-cell cytokines in early arthritis (day 13), and prolonged TNF and TGF-β expression, which reflected disease progression. IL-4 mRNA expression increased in the later stages of AA. Synovial T-cell numbers transiently increased at day 6, and remained high from days 13–28. Increased pro-inflammatory cytokine expression, including IL-17, in the ILN reflects the initiating events in the early stage of disease. IL-17 may therefore play an important role in the pathogenesis of AA. The increase in IL-4 (an anti-inflammatory cytokine) in the SM in the later stages of AA suggests that IL-4 is involved in the spontaneous resolution of AA. The initial increase in IFN-γ in the ILN may reflect a pro-inflammatory response, while the prolonged secondary increase may indicate activation of regulatory T-cells. PMID:11298138

  14. Synovial membrane immunohistology in early-untreated rheumatoid arthritis reveals high expression of catabolic bone markers that is modulated by methotrexate

    PubMed Central

    2013-01-01

    Introduction We aimed to investigate the expression and therapeutic modulation of the receptor activator of the NF-κB ligand (RANKL) system in early-untreated rheumatoid arthritis (RA). Methods In this study, 15 patients with newly diagnosed RA (median symptom duration 7 months) were started on methotrexate (MTX) 20 mg weekly. Synovial biopsies were obtained by needle arthroscopy at baseline and 8 weeks after initiation of therapy. X-rays of the hands and feet were obtained at baseline and 1 year after diagnosis. Immunohistochemistry was performed to detect RANKL, receptor activator of nuclear factor-κB (RANK) and osteoprotegerin (OPG) in the synovial biopsies. The in vitro effect of MTX was tested on RA-derived primary fibroblasts and the osteoblasts-like osteosarcoma cell line (rtPCR, Western blot and ELISA) and in osteoclasts (tartrate-resistant acid phosphatase staining and dentine pit formation assay). Results MTX decreased synovial cellularity as well as RANK expression and the RANKL/OPG ratio. We confirmed this effect by a decrease of the mRNA and protein RANKL/OPG ratio in synovial-derived fibroblasts and osteoblasts-like tumoral cells exposed in vitro to methotrexate. Supernatants from MTX treated osteoblasts-like tumoral cells prevented pre-osteoclast formation in the absence of exogenous RANKL. Furthermore, MTX blocked osteoclastogenesis from peripheral blood mononuclear cells despite the presence of macrophage colony stimulating factor and RANKL, which indicates that MTX directly inhibits osteoclastogenesis. Conclusions The synovial membrane of early-untreated RA is characterized by a high RANKL/OPG ratio that can be reversed by methotrexate. PMID:24295447

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

    SciTech Connect

    Umar, Sadiq; Hedaya, Omar; Singh, Anil K.; Ahmed, Salahuddin

    2015-09-15

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

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

    PubMed

    Umar, Sadiq; Hedaya, Omar; Singh, Anil K; Ahmed, Salahuddin

    2015-09-15

    Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced by monocytes/macrophage that plays a pathological role in rheumatoid arthritis (RA). In this study, we investigate the effect of thymoquinone (TQ), a phytochemical found in Nigella sativa, in regulating TNF-α-induced RA synovial fibroblast (RA-FLS) activation. Treatment with TQ (1-5μM) had no marked effect on the viability of human RA-FLS. Pre-treatment of TQ inhibited TNF-α-induced interleukin-6 (IL-6) and IL-8 production and ICAM-1, VCAM-1, and cadherin-11 (Cad-11) expression in RA-FLS (p<0.01). Evaluation of the signaling events showed that TQ inhibited TNF-α-induced phospho-p38 and phospho-JNK expression, but had no inhibitory effect on NF-κB pathway, in RA-FLS (p<0.05; n=4). Interestingly, we observed that selective down-regulation of TNF-α-induced phospho-p38 and phospho-JNK activation by TQ is elicited through inhibition of apoptosis-regulated signaling kinase 1 (ASK1). Furthermore, TNF-α selectively induced phosphorylation of ASK1 at Thr845 residue in RA-FLS, which was inhibited by TQ pretreatment in a dose dependent manner (p<0.01). Pre-treatment of RA-FLS with ASK1 inhibitor (TC ASK10), blocked TNF-α induced expression of ICAM-1, VCAM-1, and Cad-11. Our results suggest that TNF-α-induced ASK1-p38/JNK pathway is an important mediator of cytokine synthesis and enhanced expression of adhesion molecule in RA-FLS and TQ, by selectively inhibiting this pathway, may have a potential therapeutic value in regulating tissue destruction observed in RA. PMID:26134265

  17. Platelet‑rich plasma promotes the migration and invasion of synovial fibroblasts in patients with rheumatoid arthritis.

    PubMed

    Yan, Shanshan; Yang, Binzhou; Shang, Chen; Ma, Zhongshuang; Tang, Zizheng; Liu, Guiping; Shen, Weigan; Zhang, Yu

    2016-09-01

    Platelet-rich plasma (PRP) is blood plasma that has been enriched with platelets, and the number of platelets is correlated with rheumatoid activity. PRP is a concentrated source of autologous platelets, and contains several different growth factors and cytokines, including platelet‑derived growth factor, transforming growth factor‑β and insulin‑like growth factor‑1, which stimulate healing of bone and soft tissue. Rheumatoid arthritis (RA) is characterized by synovial hyperplasia, cell activation, articular inflammation and invasion of the synovium into the adjacent bone and cartilage. The adhesion of fibroblast‑like synoviocytes (FLSs) onto the extracellular matrix (ECM), migration and invasion are important for the erosion and destruction of the articular cartilage of patients with RA. The aim of the present study was to investigate the effects of PRP on the adhesion, migration and invasion of RA‑FLSs. Scratch and Transwell migration assays determined that PRP at a concentration of 2 and 5% significantly enhanced the migration ability of RA‑FLSs. Treatment of RA‑FLSs with 2 and 5% PRP promoted the adhesion and invasion of the cells. Additionally, the immunofluorescence assay revealed that PRP induced a decrease in the number of centrally located stress fibers and led to an increase in the formation of filopodia and lamellipodia in the detectable leading edge protrusions in RA‑FLSs. In addition, reverse transcription‑quantitative polymerase chain reaction and western blot analysis determined that PRP upregulated the protein and mRNA expression levels of matrix metalloproteinase‑1 (MMP‑1). In conclusion, the promotion of RA‑FLS cell migration, invasion and adhesion on the ECM by PRP may be modulated through the upregulation of MMP‑1 expression and the induction of actin cytoskeletal reorganization. PMID:27431382

  18. Recovery of microorganisms from synovial and pleural fluids of animals using hyperosmolar media.

    PubMed

    Buchanan, A M; Davis, D C; Pedersen, N C; Beaman, B L

    1982-03-01

    L-phase (CWD) broth and plate media were used in parallel with conventional microbiological media during a 3-year period for culturing synovial and pleural fluids of animals. Two kinds of recoveries were obtained where parallel conventional methods were negative: (1) parent or normal bacteria, in very low numbers; and (2) Type B CWD variants in equally low numbers. Organisms in group 1 were: Streptococcus zooepidemicus from horses (2x); beta-hemolytic streptococci, Lancefield Gp. G (2x); Staphylococcus aureus; Actinobacillus, and Actinomyces viscosus. Group 2 consisted of Bacteroides sp., Propionibacterium acnes, and three "Nocardia-like" sp. Catalase + Actinomyces was not recovered equally well on CWD plates as on conventional media with fluids obtained during ampicillin treatment. This occurred in spite of the fact that the CWD media was shown to support growth and reversion of laboratory induced L-phase variants of Nocardia caviae and N. asteroides, and had facilitated recovery of a Bacteroides L-phase variant from a pleural fluid. The nature of this fault in the media is under investigation in this laboratory. PMID:7101719

  19. The influence of hydrostatic pressure on trans-synovial fluid movement and on capsular expansion in the rabbit knee.

    PubMed

    Levick, J R

    1979-04-01

    1. The flow of Ringer solution or paraffin oil from an infusion reservoir into the cavity of the knee (stifle) joint was measured in anesthetized rabbits, as intraarticular pressure was progressively elevated from its intrinsic slightly subatmospheric value to +25 cm H2O. 2. Paraffin oil did not penetrate the tissues lining the joint cavity, yet a continuous flow of oil occurred into the joint at pressures over +2 cm H2O. It was concluded that the joint investment behaved as a visco-elastic tissue. 3. Trans-synovial flow of Ringer solution was calculated by correcting the observed inflow for visco-elastic expansion of the joint capsule. At intra-articular pressures +2 to +9 cm H2O, trans-synovial flow increased at an average rate of 0.49 microliter min-1.cm H2O-1. The hydraulic conductivity of the synovium was therefore similar to that of subcutaneous connective tissue. At around +9 cm H2O, the 'breaking pressure', the slope of the pressure-flow relationship increased by almost sixfold to 2.81 microliter min-1.cm H2O-1. 4. Changes in joint visco-elasticity, synovial surface area, blood pressure, colloid osmotic pressure of plasma and of joint fluid, and inflammation were excluded as explanations of the marked increase in rate of fluid absorption, which is tentatively attributed to increases in synovial hydraulic conductivity. Some physiological and clinical implications of the data are discussed. PMID:458708

  20. Effects of regional limb perfusion volume on concentrations of amikacin sulfate in synovial and interstitial fluid samples from anesthetized horses.

    PubMed

    Godfrey, Jennifer L; Hardy, Joanne; Cohen, Noah D

    2016-06-01

    OBJECTIVE To evaluate the effect of volume of IV regional limb perfusion (IVRLP) on amikacin concentrations in synovial and interstitial fluid of horses. ANIMALS 8 healthy adult horses. PROCEDURES Each forelimb was randomly assigned to receive IVRLP with 4 mL of amikacin sulfate solution (250 mg/mL) plus 56 mL (total volume, 60 mL) or 6 mL (total volume, 10 mL) of lactated Ringer solution. Horses were anesthetized, and baseline synovial and interstitial fluid samples were collected. A tourniquet was placed, and the assigned treatment was administered via the lateral palmar digital vein. Venous blood pressure in the distal portion of the limb was recorded. Additional synovial fluid samples were collected 30 minutes (just before tourniquet removal) and 24 hours after IVRLP began; additional interstitial fluid samples were collected 6 and 24 hours after IVRLP began. RESULTS 30 minutes after IVRLP began, mean amikacin concentration in synovial fluid was significantly greater for the large-volume (459 μg/mL) versus small-volume (70 μg/mL) treatment. Six hours after IVRLP, mean concentration in interstitial fluid was greater for the large-volume (723 μg/mL) versus small-volume (21 μg/mL) treatment. Peak venous blood pressure after large-volume IVRLP was significantly higher than after small-volume IVRLP, with no difference between treatments in time required for pressure to return to baseline. CONCLUSIONS AND CLINICAL RELEVANCE Study findings suggested that large-volume IVRLP would deliver more amikacin to metacarpophalangeal joints of horses than would small-volume IVRLP, without a clinically relevant effect on local venous blood pressure, potentially increasing treatment efficacy. PMID:27227495

  1. Comprehensive protein profiling of synovial fluid in osteoarthritis following protein equalization

    PubMed Central

    Peffers, M.J.; McDermott, B.; Clegg, P.D.; Riggs, C.M.

    2015-01-01

    Summary Objective The aim of the study was to characterise the protein complement of synovial fluid (SF) in health and osteoarthritis (OA) using liquid chromatography mass spectrometry (LC-MS/MS) following peptide-based depletion of high abundance proteins. Design SF was used from nine normal and nine OA Thoroughbred horses. Samples were analysed with LC-MS/MS using a NanoAcquity™ LC coupled to an LTQ Orbitrap Velos. In order to enrich the lower-abundance protein fractions protein equalisation was first undertaken using ProteoMiner™. Progenesis-QI™ LC-MS software was used for label-free quantification. In addition immunohistochemistry, western blotting and mRNA expression analysis was undertaken on selected joint tissues. Results The number of protein identifications was increased by 33% in the ProteoMiner™ treated SF compared to undepleted SF. A total of 764 proteins (462 with≥2 significant peptides) were identified in SF. A subset of 10 proteins were identified which were differentially expressed in OA SF. S100-A10, a calcium binding protein was upregulated in OA and validated with western blotting and immunohistochemistry. Several new OA specific peptide fragments (neopeptides) were identified. Conclusion The protein equalisation method compressed the dynamic range of the synovial proteins identifying the most comprehensive SF proteome to date. A number of proteins were identified for the first time in SF which may be involved in the pathogenesis of OA. We identified a distinct set of proteins and neopeptides that may act as potential biomarkers to distinguish between normal and OA joints. PMID:25819577

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

    PubMed

    Liram, N; Gomori, M; Perouansky, M

    2000-01-01

    Of the 600 species of sea urchins, approximately 80 may be venomous to humans. The long spined or black sea urchin, Diadema setosum may cause damage by the breaking off of its brittle spines after they penetrate the skin. Synovitis followed by arthritis may be an unusual but apparently not a rare sequel to such injury, when implantation occurs near a joint. In this case report, osseous changes were not seen by plain x-rays. Magnetic resonance imaging (MRI) was used to expose the more salient features of both soft tissue and bone changes of black sea urchin puncture injury 30 months after penetration. In all likelihood, this type of injury may be more common than the existing literature at present suggests. It is believed to be the first reported case in this part of the world as well as the first MRI study describing this type of joint pathology. Local and systemic reactions to puncture injuries from sea urchin spines have been described previously. These may range from mild, local irritation lasting a few days to granuloma formation, infection and on occasions systemic illness. The sea urchin spines are composed of calcium carbonate with proteinaceous covering. The covering tends to cause immune reactions of variable presentation. There are only a handful of reported cases with sea urchin stings on record, none of them from the Red Sea. However, this condition is probably more common than is thought and can present difficulty in diagnosis. In this case report, the inflammation responded well to heat treatment, mobilization and manipulation of the joint in its post acute and chronic stages. As some subtle changes in soft tissues and the changes in bone were not seen either on plain x-rays or ultrasound scan, gadolinium-enhanced MRI was used to unveil the marked changes in the joint. PMID:10689244

  3. Lipid peroxidation-mediated inflammation promotes cell apoptosis through activation of NF-κB pathway in rheumatoid arthritis synovial cells.

    PubMed

    Yin, Geng; Wang, Ying; Cen, Xiao-Min; Yang, Min; Liang, Yan; Xie, Qi-Bing

    2015-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of multiple joints. The central pathogenesis of RA is the proliferation of synovial fibroblasts in response to inflammatory cytokines. However, some of the targeted therapies for inflammation reactions do not display significant clinical improvement after initiation of therapy. Thus, the relationship between inflammatory responses and RA therapy is still incompletely understood. In the present study, we proposed to determine whether enhanced inflammations may lead to cell apoptosis in rheumatoid arthritis synoviocytes. Our results indicated that products of lipid peroxidations, 4-HNE, may induce synovial intrinsic inflammations by activating NF-κB pathways and it may lead to cell apoptosis. Pharmacological inhibition of NF-κB activation may reduce the 4-HNE mediated inflammation responses and subsequent cell apoptosis. Our results may help to clarify the role of inflammations on RA development and imply that blocking NF-κB activation may be partly beneficial for human RA therapy. These findings might provide a mechanism-based rationale for developing new strategy to RA clinical therapy. PMID:25741130

  4. Pharmacokinetics of danofloxacin and N-desmethyldanofloxacin in adult horses and their concentration in synovial fluid.

    PubMed

    Lopez, B S; Giguère, S; Berghaus, L J; Mullins, M A; Davis, J L

    2015-04-01

    The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N-desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N-desmethyldanofloxacin were measured by UPLC-MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half-life of 8.00 ± 0.48 h. Maximum plasma concentration (Cmax ) of N-desmethyldanofloxacin (0.151 ± 0.038 μg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 μg/mL) than after IG administration (0.99 ± 0.1 μg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 μg/mL) and i.m. (0.70 ± 0.35 μg/mL) than after IG (0.20 ± 0.12 μg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 μg/mL for i.v. and i.m. administration and 0.12 μg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50. PMID:25224604

  5. Identification of prostaglandin E2 and leukotriene B4 in the synovial fluid of painful, dysfunctional temporomandibular joints.

    PubMed

    Quinn, J H; Bazan, N G

    1990-09-01

    It has been hypothesized that prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) should be present in the synovial fluid of inflamed, dysfunctional temporomandibular joints. An assay to identify PGE2 and LTB4 and platelet-activating factor (PAF) was used, and a strong correlation between the levels of these lipid mediators of pain and inflammation and an index of clinical joint pathology was found. PMID:2168477

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

    PubMed Central

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

    2009-01-01

    Objective: To determine which of the changes in synovial tissue correlates best with clinical response associated with effective therapy (adalimumab) to facilitate the planning of future studies with therapeutic agents for psoriatic arthritis (PsA). Methods: A total of 24 patients with active PsA were randomised to receive adalimumab (n = 12) or placebo (n = 12) for 4 weeks. Synovial biopsies were obtained before and after 4 weeks of treatment. Immunohistochemical analysis was performed to characterise the cell infiltrate, expression of cytokines and matrix metalloproteinases (MMPs) and vascularity. Sections were analysed by digital image analysis. Statistical analysis was performed using covariance analysis. Results: The mean Disease Activity Score in 28 joints (DAS28) after 4 weeks was 1.92 units lower (95% confidence interval (CI) 1.07 to 2.77) after adalimumab therapy compared with placebo. Paired pretreatment and post-treatment synovial samples were available from 19 patients. Many cell types were reduced after adalimumab treatment compared to placebo. After applying a ranked analysis of covariance (ANCOVA) model to correct for baseline imbalances, a significant effect of treatment was observed on CD3-positive cells: there was a median reduction of 248 cells/mm2 after adalimumab versus placebo treatment (p = 0.035). In addition, the expression of MMP13 was significantly reduced after active treatment: the integrated optical density (IOD)/mm2 was 18 190 lower after adalimumab treatment as compared to placebo (p = 0.033). Conclusion: Adalimumab therapy in PsA is associated with a marked reduction in T cell infiltration and MMP13 expression in synovial tissue, suggesting that these parameters could be used as biomarkers that are sensitive to change after active treatment in small proof of concept studies in PsA. PMID:18647851

  7. Inhibitor-free DNA for real-time PCR analysis of synovial fluid from horses, cattle and pigs.

    PubMed

    Schneeweiss, Wilfried; Stanek, Christian; Wagner, Martin; Hein, Ingeborg

    2007-03-31

    The potential of five different commercial DNA isolation methods to remove real-time PCR inhibitors from the synovial fluid of horses, cattle and pigs was investigated. All kits with the exception of one included a silica column-based purification of the DNA. With the fifth kit, DNA purification is achieved by removing contaminating macromolecules by a desalting process. We used a recently developed method based on comparison of the real-time PCR signal of an artificial target incorporated into each PCR reaction in the presence of the isolated DNA from the sample, and in control samples containing water instead of isolated DNA. This was followed by statistical analysis of the data. Inhibition and subsequent reduction of the endpoint fluorescence in the real-time PCR reaction was encountered in many cases. Less frequently, the target copy number in the samples was underestimated. However, we found no experimental evidence of a negative influence of the reduced endpoint fluorescence signal on the detection limit of the real-time PCR assay. All kits tested were useful for analyzing pelleted synovial fluid from horses, cattle and pigs. When analyzing non-pelleted synovial fluid, three kits - two based on silica columns and one employing a desalting process - yielded inhibitor-free DNA for real-time PCR analysis. PMID:17222992

  8. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis.

    PubMed

    Kriegsmann, Mark; Randau, Thomas M; Gravius, Sascha; Lisenko, Katharina; Altmann, Carolin; Arens, Norbert; Kriegsmann, Jörg

    2016-07-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease with a heterogeneous clinical presentation affecting about 1 % of adults in developed countries. Currently, the diagnosis is based on the revised criteria of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) from 2010. These criteria include clinical and laboratory parameters. Because of the variability of the clinical picture, delayed diagnosis of RA occurs in a significant subset of patients. Therefore, the discovery of novel biomarkers that improve the diagnosis of RA is of particular interest. Recently, it became evident that miRNAs have regulatory activities in physiologic processes and human diseases. Upregulation of miR-146a, miR-155, and miR-223 has been shown in various compartments such as serum, blood, synovial fluid, and tissues in patients with RA. A total of 87 samples were analyzed (RA 50, osteoarthritis (OA) 37). RNA was isolated from formalin-fixed paraffin-embedded synovial tissue (FFPE). The relative expression of miR-146a, miR-155, and miR-223 was determined by comparison to a housekeeping RNA molecule (snRNA U6) and an RNA pool from histologically and clinically verified OA samples. miR-146a, miR-155, and miR-223 were significantly elevated in RA compared to OA synovial tissues (p < 0.001). A strong correlation between the miRNAs could be observed. The sensitivity and specificity for the detection of RA were 0.76/0.80 (miR-146a), 0.80/0.95 (miR-155), and 0.86/0.81 (miR-223). The combination of miR-155 and miR-223 resulted in the highest area under the curve (AUC 0.92) with a sensitivity and specificity of 0.84/0.91, respectively. Significantly higher expression levels of miR-146a, miR-155, and miR-223 in FFPE synovial tissue samples of patients with established RA compared to patients with OA were shown. The usefulness of these miRs for the differential diagnosis of early phases of RA against OA remains to be investigated. PMID:27079198

  9. Synovial fluid pretreatment with hyaluronidase facilitates isolation of CD44+ extracellular vesicles.

    PubMed

    Boere, Janneke; van de Lest, Chris H A; Libregts, Sten F W M; Arkesteijn, Ger J A; Geerts, Willie J C; Nolte-'t Hoen, Esther N M; Malda, Jos; van Weeren, P René; Wauben, Marca H M

    2016-01-01

    Extracellular vesicles (EVs) in synovial fluid (SF) are gaining increased recognition as important factors in joint homeostasis, joint regeneration, and as biomarkers of joint disease. A limited number of studies have investigated EVs in SF samples of patients with joint disease, but knowledge on the role of EVs in healthy joints is lacking. In addition, no standardized protocol is available for isolation of EVs from SF. Based on the high viscosity of SF caused by high concentrations of hyaluronic acid (HA) - a prominent extracellular matrix component - it was hypothesized that EV recovery could be optimized by pretreatment with hyaluronidase (HYase). Therefore, the efficiency of EV isolation from healthy equine SF samples was tested by performing sequential ultracentrifugation steps (10,000g, 100,000g and 200,000g) in the presence or absence of HYase. Quantitative EV analysis using high-resolution flow cytometry showed an efficient recovery of EVs after 100,000g ultracentrifugation, with an increased yield of CD44+ EVs when SF samples were pretreated with HYase. Morphological analysis of SF-derived EVs with cryo-transmission-electron microscopy did not indicate damage by high-speed ultracentrifugation and revealed that most EVs are spherical with a diameter of 20-200 nm. Further protein characterization by Western blotting revealed that healthy SF-derived EVs contain CD9, Annexin-1, and CD90/Thy1.1. Taken together, these data suggest that EV isolation protocols for body fluids that contain relatively high amounts of HA, such as SF, could benefit from treatment of the fluid with HYase prior to ultracentrifugation. This method facilitates recovery and detection of CD44+ EVs within the HA-rich extracellular matrix. Furthermore, based on the findings presented here, it is recommended to sediment SF-derived EVs with at least 100,000g for optimal EV recovery. PMID:27511891

  10. Synovial fluid pretreatment with hyaluronidase facilitates isolation of CD44+ extracellular vesicles

    PubMed Central

    Boere, Janneke; van de Lest, Chris H. A.; Libregts, Sten F. W. M.; Arkesteijn, Ger J. A.; Geerts, Willie J. C.; Nolte-'t Hoen, Esther N. M.; Malda, Jos; van Weeren, P. René; Wauben, Marca H. M.

    2016-01-01

    Extracellular vesicles (EVs) in synovial fluid (SF) are gaining increased recognition as important factors in joint homeostasis, joint regeneration, and as biomarkers of joint disease. A limited number of studies have investigated EVs in SF samples of patients with joint disease, but knowledge on the role of EVs in healthy joints is lacking. In addition, no standardized protocol is available for isolation of EVs from SF. Based on the high viscosity of SF caused by high concentrations of hyaluronic acid (HA) – a prominent extracellular matrix component – it was hypothesized that EV recovery could be optimized by pretreatment with hyaluronidase (HYase). Therefore, the efficiency of EV isolation from healthy equine SF samples was tested by performing sequential ultracentrifugation steps (10,000g, 100,000g and 200,000g) in the presence or absence of HYase. Quantitative EV analysis using high-resolution flow cytometry showed an efficient recovery of EVs after 100,000g ultracentrifugation, with an increased yield of CD44+ EVs when SF samples were pretreated with HYase. Morphological analysis of SF-derived EVs with cryo-transmission-electron microscopy did not indicate damage by high-speed ultracentrifugation and revealed that most EVs are spherical with a diameter of 20–200 nm. Further protein characterization by Western blotting revealed that healthy SF-derived EVs contain CD9, Annexin-1, and CD90/Thy1.1. Taken together, these data suggest that EV isolation protocols for body fluids that contain relatively high amounts of HA, such as SF, could benefit from treatment of the fluid with HYase prior to ultracentrifugation. This method facilitates recovery and detection of CD44+ EVs within the HA-rich extracellular matrix. Furthermore, based on the findings presented here, it is recommended to sediment SF-derived EVs with at least 100,000g for optimal EV recovery. PMID:27511891

  11. A crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the reticuloendothelial system in mediating experimental arthritis

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Biologics directed against tumor-necrosis-factor (TNF)-α are efficacious in the treatment of RA. However, the role of TNF receptor-1 (TNFR1) in mediating the TNFα effects in RA has not been elucidated and conflicting data exist in experimental arthritis models. The objective is to investigate the role of TNFR1 in the synovial lining cells (SLC) and the reticuloendothelial system (RES) during experimental arthritis. Methods Third generation of adenovirus serotype 5 were either injected locally in the knee joint cavity or systemically by intravenous injection into the retro-orbital venous sinus to specifically target SLC and RES, respectively. Transduction of organs was detected by immunohistochemistry of the eGFP transgene. An adenoviral vector containing a short hairpin (sh) RNA directed against TNFR1 (HpTNFR1) was constructed and functionally evaluated in vitro using a nuclear factor-kappaB (NF-κB) reporter assay and in vivo in streptococcal cell wall-induced arthritis (SCW) and collagen-induced arthritis (CIA). Adenoviruses were administered before onset of CIA, and the effect of TNFR1 targeting on the clinical development of arthritis, histology, quantitative polymerase chain reaction (qPCR), cytokine analyses and T-cell assays was evaluated. Results Systemic delivery of Ad5.CMV-eGFP predominantly transduced the RES in liver and spleen. Local delivery transduced the synovium and not the RES in liver, spleen and draining lymph nodes. In vitro, HpTNFR1 reduced the TNFR1 mRNA expression by three-fold resulting in a 70% reduction of TNFα-induced NF-κB activation. Local treatment with HpTNFR1 markedly reduced mRNA and protein levels of interleukin (IL)-1β and IL-6 in SLC during SCW arthritis and ameliorated CIA. Systemic targeting of TNFR1 in RES of liver and spleen by systemic delivery of Ad5 virus encoding for a small hairpin RNA against TNFR1

  12. Histamine and substance P in synovial fluid of patients with temporomandibular disorders.

    PubMed

    Li, W; Long, X; Jiang, S; Li, Y; Fang, W

    2015-05-01

    Although psychosocial factors and malocclusion are regarded as potential causes of temporomandibular disorders (TMD), the underlying pathogenesis is poorly understood. Recent studies suggest that substance P (SP), which has been associated with both psychosocial factors and malocclusion, and histamine, whose release can be induced by SP, may be implicated in the pathogenetic process. This study was designed to measure the concentration of histamine and SP in synovial fluid (SF) of both 38 patients with TMD and 11 healthy controls, and analyse the correlation between histamine and SP. Patients with TMD were divided into three subgroups: displaced disc with reduction (DDR), displaced disc without reduction (DDNR) and osteoarthritis (OA), with 10, 13, 15 subjects in every subgroup, respectively. After collecting SF samples, histamine and SP levels were measured by enzyme-linked immunosorbent assay analysis (ELISA) and calibrated by bicinchoninic acid (BCA)-quantified protein level in the samples. The results suggest that OA group presented a significantly higher level of both histamine and SP than DDNR, DDR and healthy control groups. Histamine or SP in DDR and DDNR groups tend to be higher than control group, but no significance was found. Painful TMJs show higher histamine and SP than painless TMJs. Correlation analysis reveals a significant correlation between histamine and SP concentrations. Collectively, this study showed the changes of histamine and SP in the SF from different stages of TMD and found a significant correlation between the two substances, suggesting their potential implication in the pathogenesis of TMD. PMID:25545415

  13. Role of Phenol-Soluble Modulins in Formation of Staphylococcus aureus Biofilms in Synovial Fluid

    PubMed Central

    Dastgheyb, Sana S.; Villaruz, Amer E.; Le, Katherine Y.; Tan, Vee Y.; Duong, Anthony C.; Chatterjee, Som S.; Cheung, Gordon Y. C.; Joo, Hwang-Soo; Hickok, Noreen J.

    2015-01-01

    Staphylococcus aureus is a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specific S. aureus surface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such as the polysaccharide intercellular adhesin (PIA), with the bacterial cell surface. Together, our findings support a two-step model of staphylococcal prosthetic joint infection: As we previously reported, interaction of S. aureus surface proteins with host matrix proteins such as fibrin initiates agglomeration; our present results show that, thereafter, the bacterial agglomerates grow to extremely large sizes owing to the lack of PSM expression under the specific conditions present in joints. Our findings provide a mechanistic explanation for the reported extreme resistance of joint infection to antibiotic treatment, lend support to the notions that Agr functionality and PSM production play a major role in defining different forms of S. aureus infection, and have important implications for antistaphylococcal therapeutic strategies. PMID:25964472

  14. Facilitation of bone resorption activities in synovial lavage fluid patients with mandibular condyle fractures.

    PubMed

    Takano, H; Takahashi, T; Nakata, A; Nogami, S; Yusa, K; Kuwajima, S; Yamazaki, M; Fukuda, M

    2016-05-01

    The aim of this study was to investigate the bone resorption effect of the mediators delivered in joint cavity of patients with mandibular condyle fractures by detecting osteoclast markers using cellular biochemistry methods, and by analysing bone resorption activities via inducing osteoclast differentiation of the infiltrated cells from arthrocentesis. Sixteen joints in 10 patients with mandibular condyle fractures were evaluated. The control group consisted of synovial fluid (SF) samples from seven joints of four volunteers who had no clinical signs or symptoms involving the temporomandibular joint (TMJ) or disc displacement. We collected SF cells from all patients during therapeutic arthrocentesis. The infiltrating cells from TMJ SF were cultured, differentiated into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and examined bone resorption activities. We also investigated factors related to osteoclast induction of SF, using ELISA procedures. Osteoclast-like cells were induced from the SF cells obtained from all patients with condylar fractures. These multinucleated giant cells were positive for TRAP and actin, and had the ability to absorb dentin slices. The levels of macrophage colony-stimulating factor (M-CSF), prostaglandin E2 (PGE2), soluble form of receptor activator of nuclear factor kappa-B ligand (sRANKL) and osteoprotegerin (OPG), in SF samples from the patients, were significantly higher than in the controls. These findings indicate that bone resorption activities in SF from patients with mandibular condyle fractures were upregulated and may participate in the pathogenesis and wound healing. PMID:26946239

  15. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis

    PubMed Central

    Gobezie, Reuben; Kho, Alvin; Krastins, Bryan; Sarracino, David A; Thornhill, Thomas S; Chase, Michael; Millett, Peter J; Lee, David M

    2007-01-01

    The development of increasingly high-throughput and sensitive mass spectroscopy-based proteomic techniques provides new opportunities to examine the physiology and pathophysiology of many biologic fluids and tissues. The purpose of this study was to determine protein expression profiles of high-abundance synovial fluid (SF) proteins in health and in the prevalent joint disease osteoarthritis (OA). A cross-sectional study of 62 patients with early OA (n = 21), patients with late OA (n = 21), and control individuals (n = 20) was conducted. SF proteins were separated by using one-dimensional PAGE, and the in-gel digested proteins were analyzed by electrospray ionization tandem mass spectrometry. A total of 362 spots were examined and 135 high-abundance SF proteins were identified as being expressed across all three study cohorts. A total of 135 SF proteins were identified. Eighteen proteins were found to be significantly differentially expressed between control individuals and OA patients. Two subsets of OA that are not dependent on disease duration were identified using unsupervised analysis of the data. Several novel SF proteins were also identified. Our analyses demonstrate no disease duration-dependent differences in abundant protein composition of SF in OA, and we clearly identified two previously unappreciated yet distinct subsets of protein profiles in this disease cohort. Additionally, our findings reveal novel abundant protein species in healthy SF whose functional contribution to SF physiology was not previously recognized. Finally, our studies identify candidate biomarkers for OA with potential for use as highly sensitive and specific tests for diagnostic purposes or for evaluating therapeutic response. PMID:17407561

  16. Effect of synovial fluid, phosphate-buffered saline solution, and water on the dissolution and corrosion properties of CoCrMo alloys as used in orthopedic implants.

    PubMed

    Lewis, A C; Kilburn, M R; Papageorgiou, I; Allen, G C; Case, C P

    2005-06-15

    The corrosion and dissolution of high- and low-carbon CoCrMo alloys, as used in orthopedic joint replacements, were studied by immersing samples in phosphate-buffered saline (PBS), water, and synovial fluid at 37 degrees C for up to 35 days. Bulk properties were analyzed with a fine ion beam microscope. Surface analyses by X-ray photoelectron spectroscopy and Auger electron spectroscopy showed surprisingly that synovial fluid produced a thin oxide/hydroxide layer. Release of ions into solution from the alloy also followed an unexpected pattern where synovial fluid, of all the samples, had the highest Cr concentration but the lowest Co concentration. The presence of carbide inclusions in the alloy did not affect the corrosion or the dissolution mechanisms, although the carbides were a significant feature on the metal surface. Only one mechanism was recognized as controlling the thickness of the oxide/hydroxide interface. The analysis of the dissolved metal showed two mechanisms at work: (1) a protein film caused ligand-induced dissolution, increasing the Cr concentration in synovial fluid, and was explained by the equilibrium constants; (2) corrosion at the interface increased the Co in PBS. The effect of prepassivating the samples (ASTM F-86-01) did not always have the desired effect of reducing dissolution. The release of Cr into PBS increased after prepassivation. The metal-synovial fluid interface did not contain calcium phosphate as a deposit, typically found where samples are exposed to calcium rich bodily fluids. PMID:15900610

  17. Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs

    SciTech Connect

    Lee, Won-Jae; Hah, Young-Sool; Ock, Sun-A.; Lee, Jae-Hoon; Jeon, Ryong-Hoon; Park, Ji-Sung; Lee, Sang-Il; Rho, Na-Young; Rho, Gyu-Jin; Lee, Sung-Lim

    2015-05-01

    The in vitro differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (P<0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (P<0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (P<0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (P<0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (P<0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial in vivo immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice. - Highlights: • Immunosuppressive capacity of BM-, SM-, and SF-MSCs was evaluated in an RA model. • Proliferation, pluripotency and chondrogenic differentiation capacity were higher in SF-MSCs. • SF-MSCs exhibited improved therapeutic effects than BM-MSCs. • SF-MSCs may have applications as immunosuppressive therapy in autoimmune diseases.

  18. Proteomic analysis of synovial fluid as an analytical tool to detect candidate biomarkers for knee osteoarthritis

    PubMed Central

    Liao, Weixiong; Li, Zhongli; Zhang, Hao; Li, Ji; Wang, Ketao; Yang, Yimeng

    2015-01-01

    We conducted research to detect the proteomic profiles in synovial fluid (SF) from knee osteoarthritis (OA) patients to better understand the pathogenesis and aetiology of OA. Our long-term goal is to identify reliable candidate biomarkers for OA in SF. The SF proteins obtained from 10 knee OA patients and 10 non-OA patients (9 of whom were patients with a meniscus injury in the knee; 1 had a discoid meniscus in the knee, and all exhibited intact articular cartilage) were separated by two-dimensional electrophoresis (2-DE). The repeatability of the obtained protein spots regarding their intensity was tested via triplicate 2-DE of selected samples. The observed protein expression patterns were subjected to statistical analysis, and differentially expressed protein spots were identified via matrix-assisted laser desorption/ionisation-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). Our analyses showed low intrasample variability and clear intersample variation. Among the protein spots observed on the gels, there were 29 significant differences, of which 22 corresponded to upregulation and 7 to downregulation in the OA group. One of the upregulated protein spots was confirmed to be haptoglobin by mass spectrometry, and the levels of haptoglobin in SF are positively correlated with the severity of OA (r = 0.89, P < 0.001). This study showed that 2-DE could be used under standard conditions to screen SF samples and identify a small subset of proteins in SF that are potential markers associated with OA. Spots of interest identified by mass spectrometry, such as haptoglobin, may be associated with OA severity. PMID:26617706

  19. Spontaneous establishment of an Epstein-Barr virus-infected fibroblast line from the synovial tissue of a rheumatoid arthritis patient.

    PubMed Central

    Koide, J; Takada, K; Sugiura, M; Sekine, H; Ito, T; Saito, K; Mori, S; Takeuchi, T; Uchida, S; Abe, T

    1997-01-01

    An Epstein-Barr virus (EBV)-infected fibroblast line, designated DSEK, was spontaneously established from synovial tissue of a patient with rheumatoid arthritis (RA). DSEK cells expressed EBV nuclear antigens EBNA-1 and EBNA-2 and latent membrane protein LMP-1. Cell surface markers of DSEK cells were similar to those of EBV-negative fibroblast clones derived from synoviocytes and were negative for lymphocyte and macrophage markers. DSEK cells expressed CD44, CD58, and HLA-DR antigens and spontaneously produced interleukin-10 basic fibroblast growth factor and transforming growth factor beta1. These results indicate that rheumatoid synoviocytes can be a target for EBV infection and suggest that EBV may play a role in the pathogenesis of RA. PMID:9032386

  20. SYNOVIAL CHONDROMATOSIS

    PubMed Central

    Lasmar, Neylor Pace; Vieira, Rodrigo Barreiros; Rosa, Juraci de Oliveira; Lasmar, Rodrigo Campos Pace; Scarpa, André Campos

    2015-01-01

    A 34-year-old male patient presented severe pain in his left knee in association with functional incapacitation, with no apparent triggering factor. He sought medical attention in December 2006, at which time he was prescribed NSAIDs. After a year, he reported increased swelling and pain at the site. He was referred to a knee specialist with a suspected meniscal injury. Upon examination, severe swelling of the joint, with movement limitation, severe pain and negative joint aspiration, was found. Since the simple radiographic results were normal, an MRI of the knee was requested. The MRI revealed a large accumulation of fluid inside the joint, together with marked synovial proliferation, especially focal thickening in clumps with an intermediate signal in T1 and T2, and a discrete hyposignal in T2 that was suggestive of pigmented villonodular synovitis with intact meniscus and ligaments. The patient underwent arthroscopy on the left knee, which revealed whitish irregular fragments, and then underwent arthrotomy with removal of the lesion and extensive synovectomy. The material was sent for anatomopathological examination, which showed the presence of synovial chondromatosis. Eight months after the surgery, the patient does not have any complaints, with a range of motion of 130° in the left knee without joint effusion or signs of inflammation. Synovial chondromatosis is a rare benign type of metaplasia of the synovial membrane that leads to the formation of cartilaginous free bodies in the joint space. It is difficult to diagnose because 95% of the nodules, when not calcified, can be overlooked radiologically. PMID:27047814

  1. [Novel immunodiagnostics for inflammatory arthritis].

    PubMed

    Wahle, M; Kling, E

    2016-05-01

    Immunodiagnostics play an important role in the differential diagnostics of arthritis but the test results must be interpreted with respect to the clinical context. The detection of antibodies against citrullinated proteins has significantly improved the immunodiagnostics of arthritis, whereas the importance of testing for rheumatoid factor has decreased due to the low specificity. Antibodies against carbamylated or oxidized proteins will expand the immunodiagnostics of arthritis (especially rheumatoid arthritis) in the future. In contrast, the determination of cytokine concentrations in plasma or synovial fluid plays a subordinate role in the differential diagnostics of arthritis. Indirect immunofluorescence continues to be the gold standard in the detection of antinuclear antibodies (ANA) and in the case of positive results further testing for antigen specificity should be carried out. The presence of ANA is not necessarily associated with autoimmune diseases. An example of a non-pathogenic ANA is anti-DFS70 antibodies. PMID:27142378

  2. Agreement of manual cell counts and automated counts of the scil Vet abc Plus(+) hematology analyzer for analysis of equine synovial fluid.

    PubMed

    Van de Water, Eline; Oosterlinck, Maarten; Duchateau, Luc; Pille, Frederik

    2016-06-01

    The purpose of this study was to determine whether the scil Vet abc Plus(+) (SCIL Animal Care Company, Altorf, France), an impedance hematology analyzer, can accurately quantify and differentiate nucleated blood cells (NBCs) in equine synovial fluid. Synovial fluid samples (n=242) in different stages of experimentally induced inflammation were analyzed with and without hyaluronidase pretreatment and compared to manual hemocytometer counts and smear reviews. No significant effect of hyaluronidase pretreatment was observed. Total nucleated cell counts of the scil Vet abc Plus(+) were significantly higher compared to the manual method (P=0.02), yet the difference was small and clinically irrelevant (ratio manual/automated count equal to 0.97 with 95% CI [0.95, 1.00]). Differential cell counts of the scil Vet abc Plus(+) were not accurate. In conclusion, the scil Vet abc Plus(+) hematology analyzer is highly accurate for quantification, but not accurate for differentiation of NBCs in equine synovial fluid. PMID:27234537

  3. Upregulation of fibroblast growth factor 1 in the synovial membranes of patients with late stage osteoarthritis.

    PubMed

    Li, R; Wang, B; He, C Q; Yang, Y Q; Guo, H; Chen, Y; Du, T H

    2015-01-01

    Osteoarthritis (OA) is a degenerative disease of the systemic joint that involves multiple cytokines and growth factors. Fibroblast growth factor 1 (FGF-1) is increased in patients with rheumatic arthritis. The aim of this study was to determine whether the expression and secretion of FGF-1 differed in synovial tissue from patients with late stage OA from that in normal tissues. We selected eight patients with late stage OA and eight healthy donors for this study. An enzyme-linked immunosorbent assay was used to determine the amount of FGF-1 in the synovial fluid and in the culture medium of synovial fibroblasts. Real time quantitative polymerase chain reaction (qPCR) analysis was performed to examine the expression levels of FGF-1 and FGF receptor 2 (FGFR2) in synovial and cartilage tissues. We detected FGF-1 in the synovial fluid from all eight donors, as well as in the culture medium of synovial fibroblasts. Synovial fluid from patients with OA and culture medium of OA synovial fibroblasts contained significantly more FGF-1 than those from controls. FGF-1 expression was also lower in the synovial membranes of normal donors than in those of OA patients. FGFR2 expression was also higher in OA cartilage than in normal cartilage. Overall, these results demonstrated that FGF-1 synthesis and secretion by synovial fibroblasts were significantly increased in OA. FGFR2 expression was also shown to be upregulated in patients with OA. These findings suggest that increased FGF-1 signaling correlates with an OA pathological condition. PMID:26400350

  4. Intraarticular volume and clearance in human synovial effusions

    SciTech Connect

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

    1985-04-01

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

  5. Arthritis

    MedlinePlus

    ... or have trouble moving around, you might have arthritis. Most kinds of arthritis cause pain and swelling in your joints. Joints ... joint can become severely damaged. Some kinds of arthritis can also cause problems in your organs, such ...

  6. Hyaluronidase treatment of synovial fluid to improve assay precision for biomarker research using multiplex immunoassay platforms.

    PubMed

    Jayadev, Chethan; Rout, Raj; Price, Andrew; Hulley, Philippa; Mahoney, David

    2012-12-14

    Synovial fluid (SF) is a difficult biological matrix to analyse due to its complex non-Newtonian nature. This can result in poor assay repeatability and potentially inefficient use of precious samples. This study assessed the impact of SF treatment by hyaluronidase and/or dilution on intra-assay precision using the Luminex and Meso Scale Discovery (MSD) multiplex platforms. SF was obtained from patients with knee osteoarthritis at the time of joint replacement surgery. Aliquots derived from the same sample were left untreated (neat), 2-fold diluted, 4-fold diluted or treated with 2mg/ml testicular hyaluronidase (with 2-fold dilution). Preparation methods were compared in a polysterene-bead Luminex 10-plex (N=16), magnetic-bead Luminex singleplex (N=7) and MSD 4-plex (N=7). Each method was assessed for coefficient of variation (CV) of replicate measurements, number of bead events (for Luminex assays) and dilution-adjusted analyte concentration. Percentage recovery was calculated for dilutions and HAse treatment. Hyaluronidase treatment significantly increased the number of wells with satisfactory bead events/region (95%) compared to neat (48%, p<0.001) in the polystyrene-bead Luminex assay, but the magnetic-bead Luminex assay achieved ≥50 bead events irrespective of treatment method. Hyaluronidase treatment resulted in lower intra-assay CVs for detectable ligands (group average CV<10%) than neat, 2-fold and 4-fold dilution (CV~25% for all, p<0.05) in both polystyrene- and magnetic-bead Luminex assays. In addition, measured sample concentrations were higher and recovery was poor (elevated) after hyaluronidase treatment. In the MSD 4-plex, within-group comparison of the intra-assay CV or concentration was not conclusively influenced by SF preparation. However, only hyaluronidase treatment resulted in CV<25% for all samples for TNF-α. There was no effect on analyte concentrations or recovery. Hyaluronidase treatment can improve intra-assay precision and assay signal

  7. Comparison of human mesenchymal stem cells derived from bone marrow, synovial fluid, adult dental pulp, and exfoliated deciduous tooth pulp.

    PubMed

    Isobe, Y; Koyama, N; Nakao, K; Osawa, K; Ikeno, M; Yamanaka, S; Okubo, Y; Fujimura, K; Bessho, K

    2016-01-01

    Populations of pluripotent stem cells were isolated from bone marrow, synovial fluid, adult dental pulp, and exfoliated deciduous teeth and their multipotentiality properties compared. Osteogenic, chondrogenic, adipogenic, and neurogenic differentiation potentials were examined. Bone marrow mesenchymal stem cells (BMMSCs) and synovial fluid-derived cells (SFCs) showed the highest levels of osteogenesis as expressed by alkaline phosphatase (ALP) activity (0.54±0.094 U/mg protein and 0.57±0.039 U/mg protein, respectively; P=0.60) and by osteocalcin (BGLAP; determined by real-time RT-PCR). SFCs showed the highest levels of chondrogenesis as expressed by ALP activity (1.75±0.097 U/mg protein) and of COL2A1 and COL10A1 by real-time PCR. In terms of adipogenesis, lipid vesicles were observed in the BMMSCs and SFCs. Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) exhibited neurogenesis potential, as shown by increases in expression of class III β-tubulin (TUBB3) and microtubule-associated protein 2 (MAP2) on RT-PCR. Variability was found in the differentiation potential corresponding to the tendency of the original tissue to differentiate. It is suggested that the cell type should be selected depending on the regenerative treatment regimen. PMID:26235629

  8. A Customized Raman System for Point-of-Care Detection of Arthropathic Crystals in the Synovial Fluid

    PubMed Central

    Li, Bolan; Yang, Shan; Akkus, Ozan

    2014-01-01

    Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) are the most frequently observed crystals in joint space, leading to painful arthropathies. Correct diagnosis of the crystal identity is critical for the appropriate course of treatment. In this work, a custom Raman device in combination with a practical and efficient sample preparation method is used for chemically selective diagnosis of MSU and CPPD crystals in an automated fashion. The samples were prepared by a brief enzymatic digestion treatment of synovial fluid followed by a customized filtration process which was able to congregate crystals over a submillimeter sized spot. The data acquisition and collection was automated to collect multiple spectra distributed over the filtration spot. The performance of the cost-efficient Raman system was compared to a research-grade high fidelity Raman instrument. The custom-designed Raman device could detect MSU crystals at sub-clinical concentration of 0.1 μg/mL, and 1 μg/mL for CPPD crystals. This practical sample preparation approach in tandem with the low-cost customized Raman device has a potential to be a novel tool for point-and-shoot Raman diagnosis of arthritic crystals in synovial fluid at the point of care. PMID:24419093

  9. Diagnostic Value of T-cell Interferon-γ Release Assays on Synovial Fluid for Articular Tuberculosis: A Pilot Study

    PubMed Central

    Cheng, Xin-He; Bian, Sai-Nan; Zhang, Yue-Qiu; Zhang, Li-Fan; Shi, Xiao-Chun; Yang, Bo; Zhang, Feng-Chun; Liu, Xiao-Qing

    2016-01-01

    Background: Tuberculosis (TB) remains a major global public health challenge. Articular TB is an important form of extrapulmonary tuberculosis, and its diagnosis is difficult because of the low sensitivity of traditional methods. The aim of this study was to analyze the diagnostic value of T-SPOT.TB on synovial fluid for the diagnosis of articular TB. Methods: Patients with suspected articular TB were enrolled consecutively between August 2011 and December 2015. T-SPOT.TB was performed on both synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs). The final diagnosis of articular TB was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on SFMCs and PBMCs were analyzed. Results: Twenty patients with suspected articular TB were enrolled. Six were diagnosed with articular TB, and 14 patients were diagnosed with other diseases. Sensitivity and specificity were 83% and 86% for T-SPOT.TB on SFMCs, and 67% and 69% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on SFMCs were 71% and 92%, respectively. The PPV and NPV were 50% and 82% for T-SPOT.TB on PBMCs. Conclusion: Sensitivity, specificity, and NPV of T-SPOT.TB on SFMCs appeared higher than that on PBMCs, indicating that T-SPOT.TB on SFMCs might be a rapid and accurate diagnostic test for articular TB. PMID:27174325

  10. Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee Joint

    PubMed Central

    Zhang, Congming; Wei, Xiaochun; Chen, Chongwei; Cao, Kun; Li, Yongping; Jiao, Qiang; Ding, Juan; Zhou, Jingming; Fleming, Braden C.; Chen, Qian; Shang, Xianwen; Wei, Lei

    2014-01-01

    To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh) in synovial fluid (SF) and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA) group by IHC and fluorescence molecular tomography in vivo respectively. Ihh expression was increased 5.2-fold in OA cartilage, 3.1-fold in relative normal OA cartilage, and 1.71-fold in OA SF compared to normal control samples. The concentrations of Ihh in cartilage and SF samples was significantly increased in early-stage OA samples when compared to normal samples (r = 0.556; p < 0.001); however, there were no significant differences between normal samples and late-stage OA samples. Up-regulation of Ihh protein was also an early event in the surgery-induced OA models. Increased Ihh is associated with the severity of OA cartilage damage. Elevated Ihh content in human knee joint synovial fluid correlates with early cartilage lesions. PMID:24786088

  11. Quantitative and qualitative analysis of polyethylene wear particles in synovial fluid of patients with total knee arthroplasty. A preliminary report.

    PubMed

    Bosco, J; Benjamin, J; Wallace, D

    1994-12-01

    Synovial fluid from 13 knees undergoing revision total knee arthroplasty was subjected to chemical digestion and ultrafiltration. Scanning electron microscopy was used to visualize high-density polyethylene particles filtered from the fluid, and the images were analyzed using digital imaging software. This data were correlated with polyethylene wear patterns seen at the time of revision surgery. Patients' prostheses with gross polyethylene wear were differentiated from those with surface deformation and burnishing. The knees had been in situ for periods ranging from 3 to 112 months, and included 6 different prosthetic designs. The average area of the polyethylene particles measured ranged from 41 to 701 mu 2, and the total number of particles identified for each sample ranged from 38 to 279 mu 2. The largest particle identified had a surface area of 17,500 mu 2. Using the fluid volume analyzed, the particle area per milliliter of synovial fluid examined was calculated, and values ranged from 6.22 x 10(4) to 2.06 x 10(6) mu 2/ml. Visualization of high-density polyethylene using scanning electron microscopy allows greater resolution of morphologic detail than is possible with routine histologic examination using light microscopy. There were trends toward increasing particle size and total particle area in patients with gross polyethylene wear. The area of high-density polyethylene per milliliter of fluid in patients with gross wear was found to be statistically greater than that of patients without gross wear (p = 0.047). This technique offers a potentially valuable method of evaluating the status of high-density-polyethylene bearing surfaces in situ using a noninvasive technique. PMID:7994947

  12. Investigation of the Frictional Response of Osteoarthritic Human Tibiofemoral Joints and the Potential Beneficial Tribological Effect of Healthy Synovial Fluid

    PubMed Central

    Caligaris, Matteo; Canal, Clare E.; Ahmad, Christopher S.; Gardner, Thomas R.; Ateshian, Gerard A.

    2009-01-01

    Objective This study tests the hypothesis that the natural progression of osteoarthritis (OA) in human joints leads to an increase in the friction coefficient. This hypothesis is based on the expectation that the wear observed in OA may be exacerbated by higher friction coefficients. A corollary hypothesis is that healthy synovial fluid (SF) may help mitigate the increase in the friction coefficient in diseased joints. Design The friction coefficient of human tibiofemoral joints with varying degrees of OA was measured in healthy bovine SF and physiological buffered saline (PBS). Two testing configurations were adopted, one that promotes sustained cartilage interstitial fluid pressurization to investigate the effectiveness of this mechanism with advancing OA, and another that allows interstitial fluid pressure to subside to investigate the effectiveness of boundary lubrication. Results Eight specimens were visually staged to be normal or mildly degenerated (stages ≤2 on a scale of 1 to 4) and eight others had progressive degeneration (stages > 2 and ≤ 3). No statistical differences were found in the friction coefficient with increasing OA, whether in migrating or stationary contact area configurations; however, the friction coefficient was significantly lower in SF than PBS in both configurations. Conclusions The friction coefficient of human tibiofemoral cartilage does not necessarily increase with naturally increasing OA, for visual stages ranging from 1 to 3. This outcome may be explained by the fact that interstitial fluid pressurization is not necessarily defeated by advancing degeneration. This study also demonstrates that healthy synovial fluid decreases the friction coefficient of OA joints relative to PBS. PMID:19410031

  13. Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis.

    PubMed Central

    Koch, A E; Kunkel, S L; Harlow, L A; Mazarakis, D D; Haines, G K; Burdick, M D; Pope, R M; Walz, A; Strieter, R M

    1994-01-01

    We and others have shown that cells obtained from inflamed joints of rheumatoid arthritis (RA) patients produce interleukin-8, a potent chemotactic cytokine for neutrophils (PMNs). However, IL-8 accounted for only 40% of the chemotactic activity for PMNs found in these synovial fluids. Currently, we have examined the production of the novel PMN chemotactic cytokine, epithelial neutrophil activating peptide-78 (ENA-78), using peripheral blood, synovial fluid, and synovial tissue from 70 arthritic patients. RA ENA-78 levels were greater in RA synovial fluid (239 +/- 63 ng/ml) compared with synovial fluid from other forms of arthritis (130 +/- 118 ng/ml) or osteoarthritis (2.6 +/- 1.8 ng/ml) (P < 0.05). RA peripheral blood ENA-78 levels (70 +/- 26 ng/ml) were greater than normal peripheral blood levels (0.12 +/- 0.04 ng/ml) (P < 0.05). Anti-ENA-78 antibodies neutralized 42 +/- 9% (mean +/- SE) of the chemotactic activity for PMNs found in RA synovial fluids. Isolated RA synovial tissue fibroblasts in vitro constitutively produced significant levels of ENA-78, and this production was further augmented when stimulated with tumor necrosis factor-alpha (TNF-alpha). In addition RA and osteoarthritis synovial tissue fibroblasts as well as RA synovial tissue macrophages were found to constitutively produce ENA-78. RA synovial fluid mononuclear cells spontaneously produced ENA-78, which was augmented in the presence of lipopolysaccharide. Immunohistochemical localization of ENA-78 from the synovial tissue of patients with arthritis or normal subjects showed that the predominant cellular source of this chemokine was synovial lining cells, followed by macrophages, endothelial cells, and fibroblasts. Synovial tissue macrophages and fibroblasts were more ENA-78 immunopositive in RA than in normal synovial tissue (P < 0.05). These results, which are the first demonstration of ENA-78 in a human disease state, suggest that ENA-78 may play an important role in the recruitment of PMNs

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

    PubMed Central

    Amanat, Suheil; Ahmed, Abdulkhaled; Armstrong, Malcolm; Sharma, Pankaj; Qamruddin, Ahmed

    2014-01-01

    We quantify the false-negative diagnostic rate of septic arthritis using Gram-stain microscopy of synovial fluid and compare this to values reported in the peer-reviewed literature. We propose a method of improving the diagnostic value of Gram-stain microscopy using Lithium Heparin containers that prevent synovial fluid coagulation. Retrospective study of the Manchester Royal Infirmary microbiology database of patients undergoing synovial fluid Gram-stain and culture between December 2003 and March 2012 was undertaken. The initial cohort of 1896 synovial fluid analyses for suspected septic arthritis was reduced to 143 after exclusion criteria were applied. Analysis of our Gram-stain microscopy yielded 111 false-negative results from a cohort size of 143 positive synovial fluid cultures, giving a false-negative rate of 78%. We report a false-negative rate of Gram-stain microscopy for septic arthritis of 78%. Clinicians should therefore avoid the investigation until a statistically significant data set confirms its efficacy. The investigation's value could be improved by using Lithium Heparin containers to collect homogenous synovial fluid samples. Ongoing research aims to establish how much this could reduce the false-negative rate. PMID:24678320

  15. Transmission electron microscopic identification of silicon-containing particles in synovial fluid: potential confusion with calcium pyrophosphate dihydrate and apatite crystals.

    PubMed Central

    Bardin, T; Schumacher, H R; Lansaman, J; Rothfuss, S; Dryll, A

    1984-01-01

    Silicon-containing particles were identified by transmission electron microscopy (TEM) in thin sections of two synovial fluids, which also contained calcium pyrophosphate dihydrate (CPPD) crystals, aspirated during acute attacks of pseudogout. Such particles, which are interpreted as probably being artefacts from glassware, were electron dense and similar in appearance to some CPPD or hydroxyapatite crystals. Images PMID:6476921

  16. Cervical myelopathy associated with extradural synovial cysts in 4 dogs.

    PubMed

    Levitski, R E; Chauvet, A E; Lipsitz, D

    1999-01-01

    Three Mastiffs and 1 Great Dane were presented to the University of Wisconsin Veterinary Medical Teaching Hospital for cervical myelopathy based on history and neurologic examination. All dogs were males and had progressive ataxia and tetraparesis. Degenerative arthritis of the articular facet joints was noted on survey spinal radiographs. Myelography disclosed lateral axial compression of the cervical spinal cord medial to the articular facets. Extradural compressive cystic structures adjacent to articular facets were identified on magnetic resonance imaging (1 dog). High protein concentration was the most important finding on cerebrospinal fluid analysis. Dorsal laminectomies were performed in all dogs for spinal cord decompression and cyst removal. Findings on cytologic examination of the cystic fluid were consistent with synovial fluid, and histopathologic results supported the diagnosis of synovial cysts. All dogs are ambulatory and 3 are asymptomatic after surgery with a follow-up time ranging from 1 to 8 months. This is the 1st report of extradural synovial cysts in dogs, and synovial cysts should be a differential diagnosis for young giant breed dogs with cervical myelopathy. PMID:10357105

  17. MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis

    PubMed Central

    Tchetverikov, I; Ronday, H; van El, B; Kiers, G; Verzijl, N; TeKoppele, J; Huizinga, T; DeGroot, J; Hanemaaijer, R

    2004-01-01

    Methods: ProMMP-1, -2, -3, -8, -9, TIMP-1, levels of MMP/α2-macroglobulin complexes, and collagen degradation products were measured by sandwich ELISA, activity assays, and HPLC in paired SF and serum samples from 15 patients with RA and 13 with OA. Results: MMPs were higher in SF of patients with RA than in OA or controls. MMP levels in SF of patients with OA were higher than in controls. In serum, levels of proMMP-3, -8 and -9 were higher in patients with RA than in OA or controls, whereas only proMMP-8 and -9 were higher in serum of patients with OA than in controls. A strong correlation was seen between serum and SF levels of MMP-8 and -9 in RA. Increased levels of MMP/α2-macroglobulin complexes indicated an MMP/TIMP imbalance in serum and SF in RA. SF hydroxyproline correlated significantly with SF levels of proMMP-9 in RA. Conclusions: Systemic MMP-8 and -9 levels represent the situation in the inflamed joint; MMP-9 is likely to be involved in degradation of joint collagen. The hypothesis of MMP/TIMP imbalance in RA is strengthened. PMID:15194590

  18. Arthritis

    MedlinePlus

    ... when taking arthritis medicines . Over-the-counter medicines: Acetaminophen (Tylenol) is often the first medicine tried. Take up to 4000 mg a day (two arthritis-strength Tylenol every 8 hours). To prevent damage to your ...

  19. Preventing Friction Induced Chondrocyte Apoptosis: A Comparison of Human Synovial Fluid and Hylan G-F 20

    PubMed Central

    Waller, Kimberly A; Zhang, Ling X; Fleming, Braden C; Jay, Gregory D

    2013-01-01

    Objectives Symptomatic osteoarthritis (OA) is a common painful disease with limited treatment options. A rising number of OA patients have been treated with intraarticular injections of hyaluronic acid, including the high molecular weight hylan G-F 20, which is injected following arthrocentesis. This study investigated the effectiveness of hylan G-F 20 to lower coefficient of friction (COF) and prevent chondrocyte apoptosis in vitro. Methods A disc-on-disc bovine cartilage bearing was used to measure the static and kinetic COF when lubricated with hylan G-F 20, human synovial fluid (HSF) and phosphate buffered saline (PBS). Following friction testing, we stained paraffin embedded sections of these cartilage bearings for activated caspase-3, a marker of apoptosis. Results Bearings lubricated with hylan G-F 20 had kinetic COF values that were similar to bearings lubricated with PBS, but significantly higher than those lubricated with HSF. There were no significant differences in static COF values in bearings lubricated with hylan G-F 20 as compared to PBS or HSF. However, bearings lubricated with HSF had a significantly lower static COF values compared to bearings lubricated with PBS. The mean percentage of caspase-3 positive chondrocytes in the superficial and upper intermediate zones of bearings lubricated with hylan G-F 20 were significantly higher when compared to bearings lubricated with HSF or unloaded controls, but significantly lower than those lubricated with PBS. Conclusion These findings indicate that joint lubrication may prevent chondrocyte apoptosis by lowering the COF. Furthermore, removal of synovial fluid prior to hylan G-F 20 injection may be detrimental to cartilage health. PMID:22660808

  20. [Synovial tumors and tumor-like lesions].

    PubMed

    Doepfer, A-K; Meurer, A

    2015-10-01

    Synovial tumors comprise a variety of lesions, including those with benign and aggressive neoplastic changes as well as inflammatory causes. In this article we focus on neoplastic tumors. Synovial tumors with other etiologies, such as sarcoidosis, granuloma, synovitis, or gouty arthritis, are not dealt with here. Through a precise differentiation between these disease entities can an optimization of treatment be achieved. PMID:26370407

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

    PubMed Central

    2012-01-01

    Background Rheumatoid arthritis (RA), a chronic autoimmune disease, affects sufferers in many different ways. Treatment of this chronic condition is particularly challenging. Traditional Chinese Medicine (TCM) provides alternatives. Bizhongxiao decoction (BZX) is a TCM complex, which has been used clinically for many years to treat RA. The purpose of this study is to compare the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels in rats with RA, and to elucidate its mechanism of action. Methods Ninety healthy normal female SD rats were randomly divided into six groups: normal (control), model, BZX decoction, and the three dismantled formulae (I: heat-clearing and detoxication, II: dissipating dampness, and III: blood circulation promotion). Apart from the normal (control) group, the rats in each group were injected subcutaneously with bovine type II collagen and complete Freund adjuvant to establish a collagen-induced arthritis model, so that inhibition of foot swelling in the rats by BZX decoction and its dismantled formulae could be observed. Immunohistochemistry was used to assess the levels of the inflammatory cytokines IL-1 and TNF in synovial joints at various time points. Results Twenty-one days after the model was established, the levels of TNF and IL-1 were significantly higher in the model group, BZX decoction group and dismantled formula groups I, II and III than in the normal controls (P < 0.05). The levels of these cytokines were significantly higher in the model group than the BZX decoction or the three dismantled formula groups (P <0.01). At longer times, the TNF and IL-1 levels in model group rose gradually; those in the BZX decoction and dismantled formula groups were gradually reduced. The cytokine levels in the BZX decoction group were lower than in the three dismantled formula groups and continued to decline. Conclusions BZX decoction and the three dismantled formulae examined down-regulated the inflammatory

  2. Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis

    PubMed Central

    Joyce-Shaikh, Barbara; Bigler, Michael E.; Chao, Cheng-Chi; Murphy, Erin E.; Blumenschein, Wendy M.; Adamopoulos, Iannis E.; Heyworth, Paul G.; Antonenko, Svetlana; Bowman, Edward P.; McClanahan, Terrill K.; Phillips, Joseph H.

    2010-01-01

    DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type–specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders. PMID:20212065

  3. Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

    PubMed

    Joyce-Shaikh, Barbara; Bigler, Michael E; Chao, Cheng-Chi; Murphy, Erin E; Blumenschein, Wendy M; Adamopoulos, Iannis E; Heyworth, Paul G; Antonenko, Svetlana; Bowman, Edward P; McClanahan, Terrill K; Phillips, Joseph H; Cua, Daniel J

    2010-03-15

    DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders. PMID:20212065

  4. Increasing production of matrix metalloproteinases, tumor necrosis factor-α, vascular endothelial growth factor and prostaglandin E2 in rheumatoid arthritis synovial fibroblasts by different adiponectin isoforms in a concentration-dependent manner.

    PubMed

    Li, B T; Zhang, F Z; Xu, T S; Ding, R; Li, P

    2015-01-01

    Adipokines have been known to play a significant role in rheumatic disease via synovial fibroblasts. However, to date, the concentration effects of adiponectin isoforms on the pathophysiology of rheumatoid arthritis (RA) have not been extensively studied. Therefore, the present study examined the different effects of the adiponectin isoforms on rheumatoid arthritis synovial fibroblasts (RASF) and investigated the relations between the concentration of individual adiponectin isoforms and the production of the inflammatory factors of RASF. Articular synovial tissues were obtained from the patients fulfilled with diagnostic criteria of RA, and health people. RASF and human fibroblast—like synoviocytes (HFLS) were isolated and cultured. They were stimulated with increasing concentrations of 25 μg/ml, 50 μg/ml, and 100μg/ml of different human adiponectin isoforms. The levels of matrix metalloproteinase (MMP)—3, MMP—10, tumor necrosis factor (TNF)—α, vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in culture supernatants were measured by immunoassays. The results showed the levels of MMP—3, MMP—10, TNF—α, VEGF and PGE2 were significantly increased in RASF which were treated with individual adiponectin isoforms compared to untreated RASF (p<0.01), and the increases also had significances compared to HFLS which were treated with the same conditions (p<0.05). Moreover, the effect of HMW (high molecular weight)/ MMW (middle molecular weight) was the strongest among them. In conclusion, all three adiponectin isoforms may contribute to proinflammatory effect by stimulating the production of MMP—3, MMP—10, TNF—α, VEGF and PGE2 of RASF in a concentration—dependent manner. HMW/MMW adiponectin could play an important role in matrix destroying and synovial vascular creating of the pathology of RA. PMID:26567601

  5. From Synovial Tissue to Peripheral Blood: Myeloid Related Protein 8/14 Is a Sensitive Biomarker for Effective Treatment in Early Drug Development in Patients with Rheumatoid Arthritis

    PubMed Central

    Choi, Ivy Y.; Gerlag, Danielle M.; Holzinger, Dirk; Roth, Johannes; Tak, Paul P.

    2014-01-01

    Objective The change in number of CD68-positive sublining macrophages in serial synovial biopsies has been successfully used to discriminate on the group level between effective and ineffective treatment during early drug development in rheumatoid arthritis (RA) patients. Measurement of a soluble biomarker would clearly have practical advantages. Therefore, we investigated the sensitivity to change of myeloid related protein (MRP)8/14 in serum. Methods 139 RA patients who received known effective biologics (infliximab, adalimumab and rituximab) and 28 RA patients who received placebo/ineffective therapies were included. MRP8/14 levels were analyzed in baseline and follow-up serum samples and the standardized response mean (SRM) was calculated to determine the sensitivity to change of MRP8/14 in comparison to C-reactive protein (CRP) levels and the disease activity score evaluated in 28 joints (DAS28). Results In patients treated with effective treatment, the SRM for MRP8/14 was moderate (0.56), but in patients treated with placebo/ineffective treatment the SRM was 0.06, suggesting that this biomarker is perhaps not susceptible to placebo effects in proof-of-concept studies of relatively short duration. In contrast, the SRM for DAS28 was high for effective treatment (1.07), but also moderate for ineffective treatment (0.58), representing the placebo effect. The SRM for CRP was low in the effective (0.33) and ineffective (0.23) treatment groups. Conclusion These data support the notion that quantification of changes in MRP8/14 serum levels could be used to predict potential efficacy of novel antirheumatic drugs in an early stage of drug development. A positive result would support the rationale for larger, conventional clinical trials to determine whether the effects are clinically relevant. PMID:25166859

  6. Influence of cartilage interstitial fluid on the mRNA levels of matrix proteins, cytokines, metalloproteases and their inhibitors in synovial membrane.

    PubMed

    Hyc, Anna; Moskalewski, Stanislaw; Osiecka-Iwan, Anna

    2016-09-01

    Articular cartilage and the synovial membrane both ensure the smooth action of synovial joints; however, the influence of chondrocytes on synovial metabolism remains unclear. The secretory activity of chondrocytes is usually studied in cell cultures and may differ from that in intact cartilage. According to McCutchen's theory of 'weeping' joint lubrication, loading of the articular cartilage during motion squeezes the fluid with lubricating properties from the cartilage. The purpose of the study was to obtain cartilage interstitial fluid (CIF) from intact cartilage and to evaluate its influence on gene expression in the synovial membrane cells. CIF was rinsed out from the cartilage of newborn rats at a pressure of three bar. The chondrocytes survived rinsing and grew in culture. Cytokines in CIF were detected using the enzyme-linked immunosorbent assay (ELISA). The influence of CIF and CIF-like cocktail (all cytokines found in CIF) on gene expression in the synovial membrane cells was studied after a 4 h-incubation, by real-time PCR. Data were analyzed using the Wilcoxon matched-pair test or by the Mann‑Whitney U test. CIF contained basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF)‑1, transforming growth factor β1 (TGFβ1), bone morphogenetic protein 7 (BMP7), macrophage (M)-colony-stimulating factor (CSF), granulocyte (G)-CSF and leukemia inhibitory factor (LIF). CIF stimulated the expression of hyaluronan synthase (HAS)1 and 2, lubricin, collagen I, versican, aggrecan, matrix metalloproteinases (MMPs)2 and 3, tissue inhibitors of metalloproteinases (TIMPs) 1-3, interleukin (IL)-6 and TGFβ1, and decreased the expression of tumor necrosis factor (TNF) and IL-1β. Incubation of the synovial membrane with CIF-like cocktail partially imitated the effects of CIF. Analysis of CIF composition may help to characterize the secretory activity of chondrocytes in their natural environment under various physiological and

  7. Destructive arthritis of the wrist and palmoplantar pustulosis.

    PubMed

    Goupille, P; Pizzuti, P; Jattiot, F; Valat, J P

    1994-01-01

    The authors report a case of destructive arthritis of the right wrist occurring in a 29-year-old Algerian man, associated with palmoplantar pustulosis and HLA B27 antigen. Joint fluid and synovial biopsy were sterile and the course was favourable with surgical synovectomy and nonsteroidal antiinflammatory drugs. Usually, arthritis associated with palmoplantar pustulosis is of the non-erosive type but cases of destructive arthritis have been reported. This condition is probably a new member of the seronegative spondylarthropathy group. PMID:8070165

  8. Intracellular and extracellular CPPD crystals are a regular feature in synovial fluid from uninflamed joints of patients with CPPD related arthropathy

    PubMed Central

    Martinez, S; Pascual, E

    2005-01-01

    Objectives: To determine whether calcium pyrophosphate dihydrate (CPPD) crystals can be found in the synovial fluid of non-inflamed joints in patients with CPPD related arthropathy; if so, to determine whether they interact with cells and produce subclinical inflammation in this setting. Methods: 74 synovial fluid samples were obtained from non-inflamed knees of 74 patients with CPPD related arthropathy. Identification of CPPD crystals and synovial fluid cell counts were done manually in undiluted samples using a haematocytometric chamber. A supravital stain (Testsimplets, Boehringer Mannheim) was used to carry out differential counts and to assess the presence of intracellular crystals. Results: All 74 samples contained CPPD crystals. The mean cell count was 301.4 cells/µl (95% confidence interval (CI), 216.6 to 386.4; range 22 to 2302.5). Mononuclear cells accounted for 83.2% (95% CI, 80.4% to 86.1%; range 43% to 99%), the rest being polymorphonuclear (PMN) cells (16.8% (95% CI, 13.9% to 19.6%; range 1% to 57%)). All the samples contained intracellular CPPD crystals, which were found in 24.0% of all the cells (95% CI, 20.1% to 27.9%; range 1% to 78%). Most of the intracellular crystals were inside mononuclear cells (22.2% of all the cells (95% CI, CI 18.5% to 25.9%)), although some PMN also contained them (1.8% of all the cells (95% CI, 1.1% to 2.4%)). Conclusions: CPPD crystals are normally found in synovial fluid of non-inflamed joints of patients with CPPD related arthropathy, and they interact with cells. The raised cell counts and percentage of PMN suggest mild subclinical inflammation in these joints. PMID:15941838

  9. B lymphocyte function in patients with rheumatoid arthritis: impact of regulatory T lymphocytes and macrophages--modulation by antirheumatic drugs.

    PubMed

    Petersen, J

    1988-04-01

    The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells

  10. Fibroblast growth factor-21 concentration in serum and synovial fluid is associated with radiographic bone loss of knee osteoarthritis.

    PubMed

    Li, Zhan-Chun; Xiao, Jie; Wang, Gang; Li, Mao-Qiang; Hu, Kong-Zu; Ma, Tao; Wang, Wei-Li; Liu, Zu-De; Zhang, Ji-Dong

    2015-04-01

    We aimed to evaluate whether FGF-21 concentration in serum and synovial fluid (SF) is associated with radiographic bone loss of knee osteoarthritis (OA). A total of 186 OA patients and 108 controls were recruited. The radiographic bone loss of knee OA was assessed by the Ahlbäck grading scale. FGF-21 concentration in serum and SF was measured by enzyme-linked immunosorbent assay (ELISA). We demonstrated that OA patients had significantly higher serum FGF-21 concentration compared with controls (204.30 [range 158.25-279.16] ng/L vs. 130.72 [range 94.93-218.03] ng/L, p < 0.01). FGF-21 concentration in serum was well correlated with that in paired SF samples (r = 0.668, p < 0.001). In OA patients, those with a higher Ahlbäck grade had significantly higher serum and SF FGF-21 concentration (p < 0.001 for both). FGF-21 concentration in serum and SF was significantly and independently associated with the Ahlbäck grade (r = 0.403, p < 0.001 and r = 0.410, p < 0.001; respectively). These findings indicated that FGF-21 might be a potential biomarker for predicting bone loss of OA. Therapeutic interventions by blocking FGF-21 signaling pathways to delay the degenerative process of OA warrants further investigations. PMID:25549692

  11. Expression of vaspin in the joint and the levels in the serum and synovial fluid of patients with osteoarthritis

    PubMed Central

    Bao, Jia-Peng; Jiang, Li-Feng; Chen, Wei-Ping; Hu, Peng-Fei; Wu, Li-Dong

    2014-01-01

    The aim of this study was to determine the expression of vaspin in the joint and investigate the distribution between paired serum and synovial fluid (SF) in osteoarthritis (OA) patients, and serum in healthy controls. The gene expression of vaspin was measured by quantitative real-time polymerase chain reaction (qPCR) in the OA joint tissues. The vaspin protein expression in the cartilage, synovium and osteophyte from OA patients who required total knee replacement (TKR) were detected by immunohistochemistry (IHC). Levels of vaspin in serum and SF were analyzed by enzyme-linked immunosorbent assay (ELISA), including 26 OA patients and 23 healthy controls. All the joint tissues including cartilage, synovium, meniscus, infrapatellar fat pad and osteophyte from OA patients expressed vaspin messenger RNA (mRNA), and the expression of vaspin protein was observed in OA cartilage, synovium and osteophyte. Furthermore, serum vaspin was reduced in OA patients compared to healthy controls, and serum vaspin levels from OA patients exceed those in the paired SF. Serum or SF vaspin were not related to age, gender, or body mass index (BMI). These results suggest that vaspin may be involved in the pathophysiology of OA and may have local effects in the joint during the process of OA. PMID:25419381

  12. Peripheral blood and synovial fluid T cells differ in their response to alloantigens and recall antigens presented by dendritic cells.

    PubMed Central

    Stagg, A J; Harding, B; Hughes, R A; Keat, A; Knight, S C

    1991-01-01

    Properties of T cells from inflammatory lesions were analysed by comparing the response of peripheral blood (PB) and synovial fluid (SF) T cells from 19 patients with a range of arthropathies to enriched allogeneic dendritic cells (DC) in a primary mixed leucocyte reaction (MLR). In 17 patients the proliferative response of SF T cells was significantly (P less than 0.05) less than that of PB lymphocytes. The reduced response of SF T cells was observed in all disease categories studied and could not be attributed to differences in cell number requirements or response kinetics. Addition of recombinant interleukin-2 enhanced the response of SF T cells in a dose-dependent manner. Cell mixing experiments suggested that active suppression was not the underlying mechanism of the poor MLR response of SF T cells. In contrast to the MLR response. SF T cells were able to mount vigorous proliferative responses to recall antigen presented by autologous antigen-presenting cells. The possibility is discussed that T cells compartmentalized at inflammatory lesions are a unique population with a diminished ability to interact with DC and respond to primary stimuli but an ability to respond to secondary antigenic challenge. PMID:1826648

  13. Tribological investigation of diamond-like carbon coated micro-dimpled surface under bovine serum and osteoarthritis oriented synovial fluid

    NASA Astrophysics Data System (ADS)

    Ghosh, Subir; Choudhury, Dipankar; Roy, Taposh; Mamat, Azuddin Bin; Masjuki, H. H.; Pingguan-Murphy, Belinda

    2015-06-01

    Osteoarthritis-oriented synovial fluid (OASF), i.e., that typical of a patient with osteoarthritis, has different physical and biological characteristics than bovine serum (BS), a lubricant widely used in biotribological investigations. Micro-dimpled and diamond-like carbon- (DLC) coated surfaces are key emerging interfaces for orthopedic implants. In this study, tribological performances of dimpled surfaces, with and without DLC coating, have been investigated under both BS and OASF. The friction tests were performed utilizing a pin on a disk tribometer, whereas contact pressure, speed, and temperature were simulated to a ‘medium walking gait’ of hip joint conditions. The mechanical properties of the specimen and the physical properties of the lubricant were characterized before the friction test. Raman analysis was conducted to identify the coating condition both before and after the test. The DLC-coated dimpled surface showed maximum hardness and residual stress. A DLC-coated dimpled surface under an OASF lubricated condition yielded a lower friction coefficient and wear compared to those of plain and dimpled specimens. The higher graphitization of coated materials with increasing load was confirmed by Raman spectroscopy.

  14. Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis

    PubMed Central

    Zhang, Yibo; Lee, Seung Yoon Celine; Zhang, Yun; Furst, Daniel; Fitzgerald, John; Ozcan, Aydogan

    2016-01-01

    Gout is a form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in a joint. Diagnosis of gout relies on identification of MSU crystals under a compensated polarized light microscope (CPLM) in synovial fluid aspirated from the patient’s joint. The detection of MSU crystals by optical microscopy is enhanced by their birefringent properties. However, CPLM partially suffers from the high-cost and bulkiness of conventional lens-based microscopy, and its relatively small field-of-view (FOV) limits the efficiency and accuracy of gout diagnosis. Here we present a lens-free polarized microscope which adopts a novel differential and angle-mismatched polarizing optical design achieving wide-field and high-resolution holographic imaging of birefringent objects with a color contrast similar to that of a standard CPLM. The performance of this computational polarization microscope is validated by imaging MSU crystals made from a gout patient’s tophus and steroid crystals used as negative control. This lens-free polarized microscope, with its wide FOV (>20 mm2), cost-effectiveness and field-portability, can significantly improve the efficiency and accuracy of gout diagnosis, reduce costs, and can be deployed even at the point-of-care and in resource-limited clinical settings. PMID:27356625

  15. Characterisation of synovial fluid and infrapatellar fat pad derived mesenchymal stromal cells: The influence of tissue source and inflammatory stimulus

    PubMed Central

    Garcia, John; Wright, Karina; Roberts, Sally; Kuiper, Jan Herman; Mangham, Chas; Richardson, James; Mennan, Claire

    2016-01-01

    The infrapatellar fat pad (FP) and synovial fluid (SF) in the knee serve as reservoirs of mesenchymal stromal cells (MSCs) with potential therapeutic benefit. We determined the influence of the donor on the phenotype of donor matched FP and SF derived MSCs and examined their immunogenic and immunomodulatory properties before and after stimulation with the pro-inflammatory cytokine interferon-gamma (IFN-γ). Both cell populations were positive for MSC markers CD73, CD90 and CD105, and displayed multipotency. FP-MSCs had a significantly faster proliferation rate than SF-MSCs. CD14 positivity was seen in both FP-MSCs and SF-MSCs, and was positively correlated to donor age but only for SF-MSCs. Neither cell population was positive for the co-stimulatory markers CD40, CD80 and CD86, but both demonstrated increased levels of human leukocyte antigen-DR (HLA-DR) following IFN-γ stimulation. HLA-DR production was positively correlated with donor age for FP-MSCs but not SF-MSCs. The immunomodulatory molecule, HLA-G, was constitutively produced by both cell populations, unlike indoleamine 2, 3-dioxygenase which was only produced following IFN-γ stimulation. FP and SF are accessible cell sources which could be utilised in the treatment of cartilage injuries, either by transplantation following ex-vivo expansion or endogenous targeting and mobilisation of cells close to the site of injury. PMID:27073003

  16. Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis

    NASA Astrophysics Data System (ADS)

    Zhang, Yibo; Lee, Seung Yoon Celine; Zhang, Yun; Furst, Daniel; Fitzgerald, John; Ozcan, Aydogan

    2016-06-01

    Gout is a form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in a joint. Diagnosis of gout relies on identification of MSU crystals under a compensated polarized light microscope (CPLM) in synovial fluid aspirated from the patient’s joint. The detection of MSU crystals by optical microscopy is enhanced by their birefringent properties. However, CPLM partially suffers from the high-cost and bulkiness of conventional lens-based microscopy, and its relatively small field-of-view (FOV) limits the efficiency and accuracy of gout diagnosis. Here we present a lens-free polarized microscope which adopts a novel differential and angle-mismatched polarizing optical design achieving wide-field and high-resolution holographic imaging of birefringent objects with a color contrast similar to that of a standard CPLM. The performance of this computational polarization microscope is validated by imaging MSU crystals made from a gout patient’s tophus and steroid crystals used as negative control. This lens-free polarized microscope, with its wide FOV (>20 mm2), cost-effectiveness and field-portability, can significantly improve the efficiency and accuracy of gout diagnosis, reduce costs, and can be deployed even at the point-of-care and in resource-limited clinical settings.

  17. Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis.

    PubMed

    Zhang, Yibo; Lee, Seung Yoon Celine; Zhang, Yun; Furst, Daniel; Fitzgerald, John; Ozcan, Aydogan

    2016-01-01

    Gout is a form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in a joint. Diagnosis of gout relies on identification of MSU crystals under a compensated polarized light microscope (CPLM) in synovial fluid aspirated from the patient's joint. The detection of MSU crystals by optical microscopy is enhanced by their birefringent properties. However, CPLM partially suffers from the high-cost and bulkiness of conventional lens-based microscopy, and its relatively small field-of-view (FOV) limits the efficiency and accuracy of gout diagnosis. Here we present a lens-free polarized microscope which adopts a novel differential and angle-mismatched polarizing optical design achieving wide-field and high-resolution holographic imaging of birefringent objects with a color contrast similar to that of a standard CPLM. The performance of this computational polarization microscope is validated by imaging MSU crystals made from a gout patient's tophus and steroid crystals used as negative control. This lens-free polarized microscope, with its wide FOV (>20 mm(2)), cost-effectiveness and field-portability, can significantly improve the efficiency and accuracy of gout diagnosis, reduce costs, and can be deployed even at the point-of-care and in resource-limited clinical settings. PMID:27356625

  18. Saline breast implant fluid collection and reactive arthritis in a patient with streptococcal toxic shock syndrome.

    PubMed

    Kohannim, Omid; Rubin, Zachary; Taylor, Mihaela

    2011-03-01

    Streptococcal toxic shock syndrome is a potentially lethal condition with an increasing incidence over the last 30 years. We present the case of a 55-year-old patient with signs and symptoms of streptococcal toxic shock syndrome. This patient's presentation was unique in that it was followed by an accumulation of fluid at her breast implant in addition to a polyarticular reactive arthritis. We propose that the patient's reactive arthritis is consistent with the diagnosis of post-streptococcal reactive arthritis, a variant of acute rheumatic fever, which similarly to its variant is immunologically driven. We hypothesize that the fluid collection around the patient's breast implant was triggered by her infection and was also immunologically mediated. PMID:21325958

  19. Acute Septic Arthritis

    PubMed Central

    Shirtliff, Mark E.; Mader, Jon T.

    2002-01-01

    Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection. PMID:12364368

  20. Effects of glucosamine-chondroitin combination on synovial fluid IL-1β, IL-6, TNF-α and PGE2 levels in internal derangements of temporomandibular joint

    PubMed Central

    Esen, Emin; Tatli, Ufuk

    2015-01-01

    Background The aim of the present study was to evaluate the effects of glucosamine-chondroitin sulphate combination on internal derangements of temporomandibular joint in clinical and biochemical manners. Material and Methods This randomized clinical study included 31 cases reporting joint tenderness, in which disc displacement was detected on MR imaging. In all patients, synovial fluid sampling was performed under local anesthesia. In the study group, the patients were prescribed a combination of 1500 mg glucosamine and 1200 mg chondroitin sulphate, while patients in the control group were only prescribed 50 mg tramadol HCl (twice daily) for pain control. After 8 weeks, synovial fluid sampling was repeated in the same manner. The levels of pain, maximum mouth opening (MMO), synovial fluid IL-1ß, IL-6, TNF-α and PGE2 measured before and after pharmacological intervention were compared. Results The reduction in pain levels was significant in both groups. There was no significant difference between two groups in terms of pain reduction. The improvement in MMO was significant in the study group but it was not in the control group. The MMO improvement was significantly higher in the study group compared to the control group. In the study group, significant decrease was observed in PGE2 level, while the decreases in IL-1β, IL-6 and TNF-α levels were not significant. In the control group, no significant decrease was observed in any of the inflammatory cytokines after 8 weeks, moreover IL-1ß and IL-6 levels were increased. Alterations of IL-1ß and IL-6 levels were significant in study group while TNF-α and PGE2 levels were not, compared to control group. Conclusions In conclusion, these results might suggest that glucosamine-chondroitin combination significantly increases the MMO and decreases the synovial fluid IL1β and IL6 levels in internal derangements of TMJ compared to tramadol. The modifications of synovial fluid TNF-α and PGE2 levels do not reach

  1. Arthritis

    MedlinePlus

    ... Difficulty moving a joint (called "limited range of motion") Some types of arthritis may cause joint deformity. ... exercise). Walking is a good example. Range of motion exercises for flexibility. Strength training for muscle tone. ...

  2. Juxtafacet Spinal Synovial Cysts

    PubMed Central

    2016-01-01

    Study Design This was a retrospective study. Purpose To study the surgical outcome of synovial cysts of the lumbar spine through posterior laminectomy in combination with transpedicular screw fixation. Overview of Literature Synovial cysts of the lumbar spine contribute significantly to narrowing of the spinal canal and lateral thecal sac and nerve root compression. Cysts form as a result of arthrotic disruption of the facet joint, leading to degenerative spondylolisthesis in up to 40% of patients. Methods Retrospective data from 6 patients, treated during the period of March 2007 to February 2011, were analyzed. All preoperative and postoperative manifestations, extension/flexion radiographs, magnetic resonance imaging, and computed tomography records were reviewed. All underwent surgery for synovial cysts with excision and decompression combined with posterior fixation. The result of surgery was evaluated with Macnab's classification. An excellent or good outcome was considered as satisfactory. Japanese Orthopedic Association Scale was used for evaluation of back pain. Results All patients included in this study had excellent outcomes as regarding to improvement of all preoperative manifestations and returning to normal daily activities. Only 2 cases developed postoperative transient cerebro-spinal fluid leak and were treated conservatively and improved during the follow up period. Conclusions Although this study included a small number of cases and we could not have statistically significant results, the good outcome of decompression of synovial cysts combined with posterior fixation and fusion encouraged us to recommend this approach for patients with juxtafacet synovial cysts. PMID:26949457

  3. Macroscopic assessment of cartilage shear: effects of counter-surface roughness, synovial fluid lubricant, and compression offset.

    PubMed

    Nguyen, Quynhhoa T; Wong, Benjamin L; Chun, June; Yoon, Yeoung C; Talke, Frank E; Sah, Robert L

    2010-06-18

    During joint articulation, cartilage is subjected to compression, shear, and sliding, mechanical factors that regulate and affect cartilage metabolism. The objective of this study was to use an in vitro material-on-cartilage shear test to elucidate the effects of counter-surface roughness (Polished, Mildly rough, and Rough), lubricants (phosphate buffered saline (PBS) and bovine synovial fluid (bSF)), and compression offset on the shearing and sliding of normal human talar cartilage under dynamic lateral displacement. Peak shear stress (sigma(xz,m)) and strain (E(xz,m)) increased with increasing platen roughness and compression offset, and were 30% higher with PBS than with bSF. Compared to PBS, bSF was more effective as a lubricant for P than for M and R platens as indicated by the higher reduction in kinetic friction coefficient (-60% vs. -20% and -19%, respectively), sigma(xz,m) (-50% vs. -14% and -17%) and E(xz,m) (-54% vs. -19% and -17%). Cartilage shear and sliding were evident for all counter-surfaces either at low compression offset (10%) or with high lateral displacement (70%), regardless of lubricant. An increase in tissue shear occurred with either increased compression offset or increased surface roughness. This material and biomechanical test system allow control of cartilage sigma(xz,m) and E(xz,m), and hence, sliding magnitude, for an imposed lateral displacement. It therefore can facilitate study of cartilage mechanobiological responses to distinct regimes of cartilage loading and articulation, such as shear with variable amounts of sliding. PMID:20189572

  4. Synovial Fluid Macrophage Migration Inhibitory Factor Levels Correlate with Severity of Self-Reported Pain in Knee Osteoarthritis Patients

    PubMed Central

    Zhang, Pei-liang; Liu, Jun; Xu, Li; Sun, Yan; Sun, Xue-cheng

    2016-01-01

    Background Inflammation is considered as one of the main pathogeneses in OA-induced pain. Macrophage migration inhibitory factor (MIF) is a well known pro-inflammatory cytokine. We aimed to determine whether MIF levels in serum and synovial fluid (SF) are associated with severity of OA-induced pain. Material/Methods We recruited 226 patients with knee OA and 106 controls. Self-reported pain severity of OA patients was evaluated using the Western Ontario McMaster University Osteoarthritis (WOMAC) pain scores. MIF levels were detected using enzyme-linked immunosorbent assay (ELISA). Results OA patients had similar serum MIF levels compared to controls (11.93 [5.68–18.10] vs. 10.06 [6.60–14.61] ng/ml, P>0.05). In OA patients, MIF levels in SF were dramatically lower compared to paired serum samples (3.39 [1.87–5.89] vs. 11.93 [5.68–18.10] ng/ml, P<0.01). MIF levels in SF were significantly correlated with WOMAC pain scores (r=0.237, P<0.001), but MIF levels in serum had no significant correlation with WOMAC pain scores (r=0.009, P=0.898). Conclusions MIF levels in SF, but not in serum, were independently associated with the severity of self-reported pain in OA patients. The inhibition of MIF signaling pathways may be a novel therapeutic approach for ameliorating OA-induced pain. PMID:27342658

  5. Cartilage Shear Kinematics During Tibio-Femoral Articulation: Effect of Acute Joint Injury & Tribosupplementation on Synovial Fluid Lubrication

    PubMed Central

    Wong, Benjamin L.; Kim, Seung Hyun Chris; Antonacci, Jennifer M.; McIlwraith, C. Wayne; Sah, Robert L.

    2009-01-01

    Objective To determine the effects of acute injury and tribosupplementation by hyaluronan (HA) on synovial fluid (SF) modulation of cartilage shear during tibio-femoral articulation. Methods Human osteochondral blocks from the lateral femoral condyle (LFC) and tibial plateau (LTP) were apposed, compressed 13%, and subjected to sliding under video microscopy. Tests were conducted with equine SF from normal joints (NL-SF), SF from acutely injured joints (AI-SF), and AI-SF to which HA was added (AI-SF+HA). Local and overall shear strain (Exz) and the lateral displacement (Δx) at which Exz reached 50% of peak values (Δx1/2) were determined. Results During articulation, LFC and LTP cartilage Exz increased with Δx and peaked when surfaces slid, with peak Exz being maintained during sliding. With AI-SF as lubricant, surface and overall Δx1/2 were ~40% and ~20% higher, respectively than values with NL-SF and AI-SF+HA as lubricant. Also, peak Exz was markedly higher with AI-SF as lubricant than with NL-SF as lubricant, both near the surface (~80%) and overall (50–200%). Following HA supplementation to AI-SF, Exz was reduced from values with AI-SF alone by 30–50% near the surface and 20–30% overall. Magnitudes of surface and overall Exz were markedly (~50–80%) higher in LTP cartilage than LFC cartilage for all lubricants. Conclusion Acute injury impairs SF function, elevating cartilage Exz markedly during tibio-femoral articulation; such elevated Exz may contribute to post-injury associated cartilage degeneration. Since HA partially restores the function of AI-SF, as indicated by Exz, tribosupplements may be beneficial in restoring cartilage mechanobiology. PMID:20004636

  6. Macroscopic Assessment of Cartilage Shear: Effects of Counter-surface Roughness, Synovial Fluid Lubricant, and Compression Offset

    PubMed Central

    Nguyen, Quynhhoa T.; Wong, Benjamin L.; Chun, June; Yoon, Yeoung C.; Talke, Frank E.; Sah, Robert L.

    2010-01-01

    During joint articulation, cartilage is subjected to compression, shear, and sliding, mechanical factors that regulate and affect cartilage metabolism. The objective of this study was to use an in vitro material-on-cartilage shear test to elucidate the effects of counter-surface roughness (Polished, Mildly rough, and Rough), lubricants (phosphate buffered saline (PBS) and bovine synovial fluid (bSF)), and compression offset on the shearing and sliding of normal human talar cartilage under dynamic lateral displacement. Peak shear stress (σxz,m) and strain (Exz,m) increased with increasing platen roughness and compression offset, and were 30% higher with PBS than with bSF. Compared to PBS, bSF was more effective as a lubricant for P than for M and R platens as indicated by the higher reduction in kinetic friction coefficient (−60% vs. − 20% and −19%, respectively), σxz,m (−50% vs. −14% and −17%) and Exz,m (−54% vs. −19% and − 17%). Cartilage shear and sliding were evident for all counter-surfaces either at low compression offset (10%) or with high lateral displacement (70%), regardless of lubricant. An increase in tissue shear occurred with either increased compression offset or increased surface roughness. This material and biomechanical test system allow control of cartilage σxz,m and Exz,m, and hence, sliding magnitude, for an imposed lateral displacement. It therefore can facilitate study of cartilage mechanobiological responses to distinct regimes of cartilage loading and articulation, such as shear with variable amounts of sliding. PMID:20189572

  7. Identification of nanobacteria in human arthritic synovial fluid by method validated in human blood and urine using 200 nm model nanoparticles.

    PubMed

    Tsurumoto, Toshiyuki; Zhu, Dan; Sommer, Andrei P

    2008-05-01

    Earlier we introduced a biosensor for the identification of nanobacteria in water drops. Here, we generalize its principle and apply it to identify nanobacteria in synovial fluid from a patient with osteoarthritis. Results indicate the prevalence of nanobacteria in the synovial fluid. The identification method is applicable to body fluids such as unfiltered human blood and urine, is independent of culturing procedures, and permits for a rapid detection of nanoparticles in liquid drops. In view of increasing clinical evidence on a contribution of nanobacteria in disease, their reported detection in HIV-infected people in South Africa, laboratory experiments indicating the excretion of viable (i.e., propagating) nanobacteria from humans via urine, the use of human excreta in agricultural irrigation, models predicting an injection of nanoaerosols contained in irrigation water enriched with human excreta into the atmosphere, and the identification of nanobacteria in the terrestrial atmosphere, promote the identification method described in this work to an important tool to monitor nanobacteria in body fluids and environmental samples. PMID:18522113

  8. Oral rosmarinic acid-enhanced Mentha spicata modulates synovial fluid biomarkers of inflammation in horses challenged with intra-articular LPS.

    PubMed

    Pearson, W; Fletcher, R S; Kott, L S

    2012-10-01

    A biological extract of high-rosmarinic acid mint (HRAM) has previously demonstrated inhibitory effects on lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)), nitric oxide (NO) and glycosaminoglycan (GAG) release in vitro. This study was undertaken to determine whether HRAM added to feed produces similar effects in horses challenged with intra-articular LPS. Eight horses received HRAM (0 or 28.1 ± 1.3 g/day; n = 4 per group) in their feed for 24 days in a blinded manner. On day 21, all horses received an intra-articular injection of LPS (0.3 ng) into their left or right intercarpal joint. Synovial fluid (SF) samples were taken on postinjection day (PID)-21 (i.e. prior to commencement of supplementation), PID0, PID0.25, PID0.5, PID1 and PID3 and analysed for PGE(2), GAG, NO, protein and total nucleated cells counts. Blood biochemistry and haematology screens were conducted at PID-21, PID0, PID1 and PID3. There was a significant reduction in LPS-induced PGE(2) and GAG in SF in horses supplemented with HRAM compared with controls and a tendency to increase complement recognition protein accumulation in synovial fluid of HRAM horses. Plasma from HRAM horses had reduced total white blood cells, segmented neutrophils (compared with baseline concentrations) and lymphocytes (compared with controls), and increased SF nucleated cell count (compared with baseline concentrations and controls). It is concluded that HRAM offered as part of the feed alter biomarkers of inflammation in SF of LPS-challenged horses. Larger studies that seek to clarify effects of HRAM on synovial fluid cell counts and possible role of HRAM-induced interference with complement signalling are warranted. PMID:22070392

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

    SciTech Connect

    Ahmed, Salahuddin; Riegsecker, Sharayah; Beamer, Maria; Rahman, Ayesha; Bellini, Joseph V.; Bhansali, Pravin; Tillekeratne, L.M. Viranga

    2013-07-15

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

  10. Femoral neck erosions: sign of hip joint synovial disease

    SciTech Connect

    Goldberg, R.P.; Weissman, B.N.; Naimark, A.

    1983-07-01

    Pathologic synovial processes in the hip joint can cause characteristic extrinsic erosions of the femoral neck, which in extreme cases produce an ''apple core'' appearance. Nine such cases of synovial diseases, including synovial osteochondromatosis, pigmented villonodular synovitis, rheumatoid arthritis, and amyloidosis, that demonstrate this radiographic finding are presented. The anatomic relations of the hip joint that result in theis appearance, differential diagnosis, and radiographic techniques useful in diagnosis are discussed.

  11. Synovial Fluid C-reactive Protein as a Diagnostic Marker for Periprosthetic Joint Infection: A Systematic Review and Meta-analysis

    PubMed Central

    Wang, Chi; Wang, Qi; Li, Rui; Duan, Jin-Yan; Wang, Cheng-Bin

    2016-01-01

    Background: Periprosthetic joint infection (PJI) is the main cause of failure following total joint arthroplasty. Until now, the diagnosis of PJI is still confronted with technical limitations, and the question of whether synovial fluid biomarker, C-reactive protein (CRP), can provide high value in the diagnosis of PJI remains unanswered and, therefore, was the aim of the study. Methods: First, we conducted a systematic review on CRP in the diagnosis of PJI by searching online databases using keywords such as “periprosthetic joint infection”, “synovial fluid”, and “C-reactive protein”. Eligible studies providing sufficient data to construct 2 × 2 contingency tables were then selected based on the list of criteria and the quality of included studies was assessed subsequently. Finally, the reported sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curve, and the area under the SROC (AUSROC) were pooled together and used to evaluate overall diagnostic performance. Results: Seven studies were included in our review, six of which comprising a total of 456 participants were further investigated in our meta-analysis. The pooled sensitivity, specificity, and DOR were 0.92 (95% confidence interval [CI]: 0.86–0.96), 0.90 (95% CI: 0.87–0.93), and 101.40 (95% CI: 48.07–213.93), respectively. The AUSROC was 0.9663 (standard error, 0.0113). Conclusions: Synovial fluid CRP is a good biomarker for the diagnosis of PJI with high sensitivity and specificity. PMID:27503025

  12. Semi-Permeable Membrane Retention of Synovial Fluid Lubricants Hyaluronan and Proteoglycan 4 for a Biomimetic Bioreactor

    PubMed Central

    Blewis, Megan E.; Lao, Brian J.; Jadin, Kyle D.; McCarty, William J.; Bugbee, William D.; Firestein, Gary S.

    2010-01-01

    Synovial fluid (SF) contains lubricant macromolecules, hyaluronan (HA), and proteoglycan 4 (PRG4). The synovium not only contributes lubricants to SF through secretion by synoviocyte lining cells, but also concentrates lubricants in SF due to its semi-permeable nature. A membrane that recapitulates these synovium functions may be useful in a bioreactor system for generating a bioengineered fluid (BF) similar to native SF. The objectives were to analyze expanded polytetrafluoroethylene membranes with pore sizes of 50 nm, 90 nm, 170 nm, and 3 μm in terms of (1) HA and PRG4 secretion rates by adherent synoviocytes, and (2) the extent of HA and PRG4 retention with or without synoviocytes adherent on the membrane. Experiment 1: Synoviocytes were cultured on tissue culture (TC) plastic or membranes ± IL-1β + TGF-β1 + TNF-α, a cytokine combination that stimulates lubricant synthesis. HA and PRG4 secretion rates were assessed by analysis of medium. Experiment 2: Bioreactors were fabricated to provide a BF compartment enclosed by membranes ± adherent synoviocytes, and an external compartment of nutrient fluid (NF). A solution with HA (1 mg/mL, MW ranging from 30 to 4,000 kDa) or PRG4 (50 μg/mL) was added to the BF compartment, and HA and PRG4 loss into the NF compartment after 2, 8, and 24 h was determined. Lubricant loss kinetics were analyzed to estimate membrane permeability. Experiment 1: Cytokine-regulated HA and PRG4 secretion rates on membranes were comparable to those on TC plastic. Experiment 2: Transport of HA and PRG4 across membranes was lowest with 50 nm membranes and highest with 3 μm membranes, and transport of high MW HA was decreased by adherent synoviocytes (for 50 and 90 nm membranes). The permeability to HA mixtures for 50 nm membranes was ~20 × 10−8 cm/s (− cells) and ~5 × 10−8 cm/s (+ cells), for 90 nm membranes was ~35 × 10−8 cm/s (− cells) and ~ 19 × 10−8 cm/s (+ cells), for 170 nm membranes was ~74 × 10−8 cm/s (± cells

  13. Hyaluronan and synovial joint: function, distribution and healing

    PubMed Central

    2013-01-01

    Synovial fluid is a viscous solution found in the cavities of synovial joints. The principal role of synovial fluid is to reduce friction between the articular cartilages of synovial joints during movement. The presence of high molar mass hyaluronan (HA) in this fluid gives it the required viscosity for its function as lubricant solution. Inflammation oxidation stress enhances normal degradation of hyaluronan causing several diseases related to joints. This review describes hyaluronan properties and distribution, applications and its function in synovial joints, with short review for using thiol compounds as antioxidants preventing HA degradations under inflammation conditions. PMID:24678248

  14. Synovial Fluid Analysis

    MedlinePlus

    ... with pseudogout. Infectious disease tests – in addition to chemistry tests, other tests may be performed to look ... Health Professionals ©2001 - by American Association for Clinical Chemistry • Contact Us | Terms of Use | Privacy We comply ...

  15. Heat Shock Protein 96 is Elevated in Rheumatoid Arthritis and Activates Macrophages primarily via TLR2 Signaling

    PubMed Central

    Huang, Qi-Quan; Sobkoviak, Rudina; Jockheck-Clark, Angela; Shi, Bo; Mandelin, Arthur M.; Tak, Paul Peter; Haines, G Kennith; Nicchitta, Christopher V.; Pope, Richard M.

    2010-01-01

    Macrophages are important mediators of chronic inflammation and are prominent in the synovial lining and sublining of patients with rheumatoid arthritis (RA). Recently, we demonstrated increased toll like receptor (TLR) 2 and 4 expression and increased response to microbial TLR2 and TLR4 ligands in macrophages from the joints of RA. The current study characterized the expression of the 96-kDa heat shock glycoprotein (gp96) in the joints of RA and its role as an endogenous TLR ligand to promote innate immunity in RA. Gp96 was increased in RA compared with osteoarthritis and arthritis-free control synovial tissues. The expression of gp96 strongly correlated with inflammation and synovial lining thickness. Gp96 was increased in synovial fluid from the joints of RA compared with disease controls. Recombinant gp96 was a potent activator of macrophages, and the activation was mediated primarily through TLR2 signaling. The cellular response to gp96 was significantly stronger with RA synovial macrophages compared to peripheral blood monocytes from RA or healthy controls. The transcription of TLR2, TNFα and IL-8, but not TLR4, was significantly induced by gp96, and the induction was significantly greater in purified RA synovial macrophages. The expression of TLR2, but not TLR4, on synovial fluid macrophages strongly correlated with the level of gp96 in the synovial fluid. The present study documents the potential role of gp96 as an endogenous TLR2 ligand in RA and provides insight into the mechanism by which gp96 promotes the chronic inflammation of RA, identifying gp96 as a potential new therapeutic target. PMID:19342676

  16. Wide-field synovial fluid imaging using polarized lens-free on-chip microscopy for point-of-care diagnostics of gout (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhang, Yibo; Lee, Seung Yoon; Zhang, Yun; Furst, Daniel; Fitzgerald, John; Ozcan, Aydogan

    2016-03-01

    Gout and pseudogout are forms of crystal arthropathy caused by monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals in the joint, respectively, that can result in painful joints. Detecting the unique-shaped, birefringent MSU/CPPD crystals in a synovial fluid sample using a compensated polarizing microscope has been the gold-standard for diagnosis since the 1960's. However, this can be time-consuming and inaccurate, especially if there are only few crystals in the fluid. The high-cost and bulkiness of conventional microscopes can also be limiting for point-of-care diagnosis. Lens-free on-chip microscopy based on digital holography routinely achieves high-throughput and high-resolution imaging in a cost-effective and field-portable design. Here we demonstrate, for the first time, polarized lens-free on-chip imaging of MSU and CPPD crystals over a wide field-of-view (FOV ~ 20.5 mm2, i.e., <20-fold larger compared a typical 20X objective-lens FOV) for point-of-care diagnostics of gout and pseudogout. Circularly polarizer partially-coherent light is used to illuminate the synovial fluid sample on a glass slide, after which a quarter-wave-plate and an angle-mismatched linear polarizer are used to analyze the transmitted light. Two lens-free holograms of the MSU/CPPD sample are taken, with the sample rotated by 90°, to rule out any non-birefringent objects within the specimen. A phase-recovery algorithm is also used to improve the reconstruction quality, and digital pseudo-coloring is utilized to match the color and contrast of the lens-free image to that of a gold-standard microscope image to ease the examination by a rheumatologist or a laboratory technician, and to facilitate computerized analysis.

  17. Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation

    SciTech Connect

    Gaston, J.S.; Strober, S.; Solovera, J.J.; Gandour, D.; Lane, N.; Schurman, D.; Hoppe, R.T.; Chin, R.C.; Eugui, E.M.; Vaughan, J.H.

    1988-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.

  18. Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction

    PubMed Central

    Mastbergen, Simon C; Jones, Elena; Calder, Stuart J; Lafeber, Floris P J G; McGonagle, Dennis

    2016-01-01

    Objectives Knee joint distraction (KJD) is a novel, but poorly understood, treatment for osteoarthritis (OA) associated with remarkable ‘spontaneous’ cartilage repair in which resident synovial fluid (SF) multipotential mesenchymal stromal cells (MSCs) may play a role. We hypothesised that SF hyaluronic acid (HA) inhibited the initial interaction between MSCs and cartilage, a key first step to integration, and postulate that KJD environment favoured MSC/cartilage interactions. Methods Attachment of dual-labelled SF-MSCs were assessed in a novel in vitro human cartilage model using OA and rheumatoid arthritic (RA) SF. SF was digested with hyaluronidase (hyase) and its effect on adhesion was observed using confocal microscopy. MRI and microscopy were used to image autologous dual-labelled MSCs in an in vivo canine model of KJD. SF-HA was investigated using gel electrophoresis and densitometry. Results Osteoarthritic-synovial fluid (OA-SF) and purified high molecular weight (MW) HA inhibited SF-MSC adhesion to plastic, while hyase treatment of OA-SF but not RA-SF significantly increased MSC adhesion to cartilage (3.7-fold, p<0.05) These differences were linked to the SF mediated HA-coat which was larger in OA-SF than in RA-SF. OA-SF contained >9 MDa HA and this correlated with increases in adhesion (r=0.880). In the canine KJD model, MSC adhesion to cartilage was evident and also dependent on HA MW. Conclusions These findings highlight an unappreciated role of SF-HA on MSC interactions and provide proof of concept that endogenous SF-MSCs are capable of adhering to cartilage in a favourable biochemical and biomechanical environment in OA distracted joints, offering novel one-stage strategies towards joint repair. PMID:25948596

  19. Attempts to identify viruses in rheumatoid synovial cells.

    PubMed Central

    Norval, M; Marmion, B P

    1976-01-01

    Synovial fibroblast cell strains derived from the synovial membranes of 7 patients with rheumatoid arthritis were examined for the presence of viruses, in particular leucoviruses. Seven similar synovial strains derived from patients with other arthritic conditions were used as a control group. Evidence of the presence of a virus or a viral genome was looked for by several methods of induction followed by 3H-uridine labelling of the cultures. In addition, the culture supernatant, after induction and after the synovial strains had been co-cultivated with a variety of cell lines from several species, was assayed for the presence of viral RNA-dependent DNA polymerase activity. The DNA-polymerase activity of the synovial cells themselves was also determined. No evidence was found by any of these techniques to indicate the presence of virus or viral information within the synovial fibroblasts. Images PMID:60087

  20. Modulation of TNF-induced macrophage polarization by synovial fibroblasts.

    PubMed

    Donlin, Laura T; Jayatilleke, Arundathi; Giannopoulou, Eugenia G; Kalliolias, George D; Ivashkiv, Lionel B

    2014-09-01

    Mesenchymal stromal cells have emerged as powerful modulators of the immune system. In this study, we explored how the human macrophage response to TNF is regulated by human synovial fibroblasts, the representative stromal cell type in the synovial lining of joints that become activated during inflammatory arthritis. We found that synovial fibroblasts strongly suppressed TNF-mediated induction of an IFN-β autocrine loop and downstream expression of IFN-stimulated genes (ISGs), including chemokines CXCL9 and CXCL10 that are characteristic of classical macrophage activation. TNF induced the production of soluble synovial fibroblast factors that suppressed the macrophage production of IFN-β, and cooperated with TNF to limit the responsiveness of macrophages to IFN-β by suppressing activation of Jak-STAT signaling. Genome-wide transcriptome analysis showed that cocultured synovial fibroblasts modulate the expression of approximately one third of TNF-regulated genes in macrophages, including genes in pathways important for macrophage survival and polarization toward an alternatively activated phenotype. Pathway analysis revealed that gene expression programs regulated by synovial fibroblasts in our coculture system were also regulated in rheumatoid arthritis synovial macrophages, suggesting that these fibroblast-mediated changes may contribute to rheumatoid arthritis pathogenesis. This work furthers our understanding of the interplay between innate immune and stromal cells during an inflammatory response, one that is particularly relevant to inflammatory arthritis. Our findings also identify modulation of macrophage phenotype as a new function for synovial fibroblasts that may prove to be a contributing factor in arthritis pathogenesis. PMID:25057003

  1. An Unusual Association: Iliopsoas Bursitis Related to Calcium Pyrophosphate Crystal Arthritis

    PubMed Central

    Di Carlo, Marco; Draghessi, Antonella; Carotti, Marina; Salaffi, Fausto

    2015-01-01

    A 71-year-old man with osteoarthritis and chondrocalcinosis came to our observation developing a swelling in the groin region after a recent left colectomy for adenocarcinoma. The imaging techniques revealed the presence of an iliopsoas bursitis in connection with the hip. The synovial fluid analysis detected the presence of calcium pyrophosphate (CPP) crystals and allowed the final and unusual diagnosis of iliopsoas bursitis related to acute CPP crystal hip arthritis. PMID:26550514

  2. Legionella pneumophila Arthritis: use of medium specific for Mycobacteria for isolation of L. pneumophila in culture of articular fluid specimens.

    PubMed

    Bemer, Pascale; Leautez, Sophie; Ninin, Emmanuelle; Jarraud, Sophie; Raffi, François; Drugeon, Henri

    2002-07-01

    We report the first case, to our knowledge, of acute purulent arthritis due to Legionella pneumophila in an immunosuppressed patient. L. pneumophila was isolated from samples of blood and articular fluid cultured with use of medium specific for mycobacteria (Bactec 13A medium). PMID:12060893

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

    PubMed

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

    2010-05-01

    Curcumin, a major component of turmeric, has been shown to exhibit anti-oxidant and anti-inflammatory activities. The present study was performed to determine whether curcumin is efficacious against both collagen-induced arthritis (CIA) in mice and IL-1beta-induced activation in fibroblast-like synoviocytes (FLSs). DBA/1 mice were immunized with bovine type II collagen (CII) and treated with curcumin every other day for 2weeks after the initial immunization. For arthritis, we evaluated the incidence of disease and used an arthritis index based on paw thickness. In vitro proliferation of CII- or concanavalin A-induced splenic T cells was examined using IFN-gamma production. Pro-inflammatory cytokines TNF-alpha and IL-1beta were examined in the mouse ankle joint and serum IgG1 and IgG2a isotypes were analyzed. The expression levels of prostaglandin E(2) (PGE(2)), cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) in human FLSs were also determined. The results showed that compared with untreated CIA mice, curcumin-treated mice downregulated clinical arthritis score, the proliferation of splenic T cells, expression levels of TNF-alpha and IL-1beta in the ankle joint, and expression levels of IgG2a in serum. Additionally, by altering nuclear factor (NF)-kappaB transcription activity in FLSs, curcumin inhibited PGE(2) production, COX-2 expression, and MMP secretion. These results suggest that curcumin can effectively suppress inflammatory response by inhibiting pro-inflammatory mediators and regulating humoral and cellular immune responses. PMID:20188213

  4. Synovial chondrosarcoma

    PubMed Central

    Confalonieri, Norberto

    2016-01-01

    Background Synovial chondrosarcoma (SCH) is a very rare tumor arising in the intra-articular cavity. In the majority of literature reports it is described as a malignant transformation of a pre-existing synovial chondromatosis (SC). We reported a systematic review of primary and secondary SCH described in the literature with the aim to recollect data from different case-reports and case-series, trying to summarize general aspects of this very rare disease. Methods We collected 42 abstracts in the form of case series and case reports, which reported 67 cases of SCH. Studies were taken into account only if they proved a histological diagnosis of SCH, either primary or secondary, with or without evidence of pre-existing SC. Results The average age of SCH was 56.9 years, with prevalence for male sex. The average time of malignant transformation was 11.2 years. The most affected joint was the knee (47.7%), followed by hip (34.3%) and ankle (5.9%). SCH was described as de novo sarcoma only in 13 cases (19%). Surgery ended up with amputation in 59.7% of cases. Local recurrence rate was 28.3%. Conclusions We concluded that prognosis of SCH is worse than conventional one and we speculated this is due to the difficult site of the tumor (intraarticular), diagnostic delay and inappropriate previous treatments. We consider that a rapid deterioration of a SC or rapid recurrence after synoviectomy should be considered suspicious of malignant transformation and should be treated in a reference center.

  5. Destruction of articular cartilage by alpha2 macroglobulin elastase complexes: role in rheumatoid arthritis

    PubMed Central

    Moore, A.; Appelboam, A.; Kawabata, K.; Da Silva, J. A P; D'Cruz, D.; Gowland, G.; Willoughby, D.

    1999-01-01

    contained α2M, and not with fractions expected to contain free enzyme.
CONCLUSIONS—The data suggest that synovial fluid α2M elastase complexes can degrade cartilage matrix in rheumatoid arthritis.

 Keywords: alpha1 antitrypsin; alpha2 macroglobulin; glycosaminoglycans; neutrophil elastase; proteoglycans; synovial fluid PMID:10343526

  6. Comparison of synovial fluid, urine, and serum ion levels in metal-on-metal total hip arthroplasty at a minimum follow-up of 18 years.

    PubMed

    Lass, Richard; Grübl, Alexander; Kolb, Alexander; Stelzeneder, David; Pilger, Alexander; Kubista, Bernd; Giurea, Alexander; Windhager, Reinhard

    2014-09-01

    Diagnosis of adverse reactions to metal debris in metal-on-metal hip arthroplasty is a multifactorial process. Systemic ion levels are just one factor in the evaluation and should not be relied upon solely to determine the need for revision surgery. Furthermore, the correlation between cobalt or chromium serum, urine, or synovial fluid levels and adverse local tissue reactions is still incompletely understood. The hypothesis was that elevated serum and urine metal-ion concentrations are associated with elevated local metal-ion concentrations in primary total hip arthroplasties (THA) and with failure of metal-on-metal articulations in the long-term. In our present study, we evaluated these concentrations in 105 cementless THA with metal-on-metal articulating surfaces with small head diameter at a minimum of 18 years postoperatively. Spearman correlation showed a high correlation between the joint fluid aspirate concentration of cobalt and chromium with the serum cobalt (r = 0.81) and chromium level (r = 0.77) in patients with the THA as the only source of metal-ions. In these patients serum metal-ion analysis is a valuable method for screening. In patients with more than one source of metal or renal insufficiency additional investigations, like joint aspirations are an important tool for evaluation of wear and adverse tissue reactions in metal-on-metal THA. PMID:24841922

  7. Increased levels of matrix metalloproteinase-3 in the sera and synovial fluids of patients with pustulotic arthro-osteitis associated with palmoplantar pustulosis: report of 2 cases.

    PubMed

    Yamamoto, Toshiyuki

    2013-07-01

    Pustulotic arthro-osteitis (PAO) is occasionally seen in patients with palmoplantar pustulosis (PPP); however, its pathogenesis is still obscure. Herein, two patients with PAO associated with PPP were described. Both patients developed hydrarthrosis on the knees, along with sternocostoclavicular pain. Detail examination revealed odontogenic infection in both cases. Matrix metalloproteinase-3 (MMP-3) is a useful marker reflecting the activity of rheumatoid arthritis. In this study, MMP-3 levels in the sera as well as joint fluids were examined. Serum MMP-3 levels were increased in both cases (274 ng/ml in Case 1 and 242 ng/ml in Case 2, normal; 17.3-59.7). Also, MMP-3 concentration in the joint fluids was markedly elevated (Case 1 > 80,000 ng/ml and 48,000 ng/ml in Case 2). Our studies suggest that MMP-3 may play a role in the pathogenesis of joint involvement of PPP. PMID:22441965

  8. Identification of the major fibroblast growth factors released spontaneously in inflammatory arthritis as platelet derived growth factor and tumour necrosis factor-alpha.

    PubMed Central

    Thornton, S C; Por, S B; Penny, R; Richter, M; Shelley, L; Breit, S N

    1991-01-01

    Rheumatoid arthritis is characterized by chronic inflammation and proliferation of a number of important elements within the joint including the synovial fibroblasts. Elevated levels of a number of cytokines such as Il-1, IL-2, IL-6, interferon-gamma (IFN-gamma), transforming growth factor-beta and tumour necrosis factor-alpha (TNF-alpha) have been detected in the synovial fluid of patients with rheumatoid arthritis and other inflammatory arthritides. It seems likely that local release of such mediators may be responsible for the proliferation and overgrowth of connective tissue elements in these disorders. In order to ascertain whether there was evidence to suggest local production or release of fibroblast growth factors in the joint in inflammatory arthritis, and to determine their identity, cells were obtained from the synovial fluid of 15 patients with chronic inflammatory arthritides. All subjects' synovial fluid cells spontaneously released growth factor activity for fibroblasts. This was present in large amounts, being detectable in culture supernatants diluted to a titre of at least 1/625. By a series of depletion experiments using solid-phase bound antibodies to cytokines, it was possible to demonstrate that this activity was due to TNF-alpha and platelet-derived growth factor (PDGF). Thus, this study showed for the first time that functionally active PDGF was released from synovial fluid cells. Both PDGF and TNF-alpha appeared to contribute in approximately equal amounts to this fibroblast growth factor activity, and were synergistic in effect. Thus this study provides evidence for the local production and release of these two cytokines and suggests that together they are the dominant factors in fibroblast proliferation within the synovial cavity. PMID:1914237

  9. Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties

    PubMed Central

    Matharu, G. S.; Mittal, S.; Pynsent, P. B.; Buckley, C. D.; Revell, M. P.

    2016-01-01

    Objectives T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty. Methods In this prospective case-control study, PB and SF were obtained from 22 patients (23 hips) undergoing revision of MoM (n = 14) and MoP (n = 9) hip arthroplasties, with eight controls provided from primary hip osteoarthritis cases awaiting arthroplasty. Lymphocyte subtypes in samples were analysed using flow cytometry. Results The percentages of CD4+ T-cell subtypes in PB were not different between groups. The CD4+ T-cells in the SF of MoM hips showed a completely different distribution of phenotypes compared with that found in the PB in the same patients, including significantly decreased CD4+ T-central memory cells (p < 0.05) and increased T-effector memory cells (p < 0.0001) in the SF. Inducible co-stimulator (ICOS) was the only co-stimulatory molecule with different expression on CD4+ CD28+ cells between groups. In PB, ICOS expression was increased in MoM (p < 0.001) and MoP (p < 0.05) cases compared with the controls. In SF, ICOS expression was increased in MoM hips compared with MoP hips (p < 0.05). Conclusions Increased expression of ICOS on CD4+ T-cells in PB and SF of patients with failed arthroplasties suggests that these cells are activated and involved in generating immune responses. Variations in ICOS expression between MoM and MoP hips may indicate different modes of arthroplasty failure. Cite this article: Professor P. A. Revell. Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties. Bone Joint Res 2016;5:52–60

  10. Evidence that Chlamydia trachomatis causes seronegative arthritis in women.

    PubMed Central

    Taylor-Robinson, D; Thomas, B J; Dixey, J; Osborn, M F; Furr, P M; Keat, A C

    1988-01-01

    Chlamydia trachomatis elementary bodies (EBs) were found in synovial membranes or synovial fluid cell deposits from five of 15 women with seronegative mono- or oligoarthritis by means of a fluorescein conjugated anti-chlamydial monoclonal antibody (Micro Trak; Syva). Genital tract specimens were taken from only five of the patients, one of whom had intra-articular EBs, but none was chlamydia positive. Six of 10 patients tested were HLA-B27 positive, and chlamydial IgG antibody, measured by microimmunofluorescence, was present at a titre of 1/greater than or equal to 64 in the sera of five of the 15 patients, three of the five having EBs in their joints. In contrast, chlamydial EBs were not detected in the joints of a control group of 10 other women, most of whom had rheumatoid arthritis. None of them was HLA-B27 positive, and only one had a chlamydial antibody titre of 1/greater than or equal to 64. Neither Mycoplasma hominis nor ureaplasmas were isolated from the synovial fluids of seven patients and five controls who were tested. Antibody to M genitalium, however, was detected in five of the 10 patients but in none of the controls. This evidence apart, there was no other suggest that mycoplasmas or ureaplasmas might be responsible for arthritis which could not be attributed to chlamydiae. PMID:3365028

  11. Macrophage migration inhibitory factor: a potential therapeutic target for rheumatoid arthritis

    PubMed Central

    Kim, Kyoung-Woon; Kim, Hae-Rim

    2016-01-01

    Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients. PMID:27169879

  12. Macrophage migration inhibitory factor: a potential therapeutic target for rheumatoid arthritis.

    PubMed

    Kim, Kyoung-Woon; Kim, Hae-Rim

    2016-07-01

    Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients. PMID:27169879

  13. Psoriatic Arthritis

    MedlinePlus

    ... physical exam as well as x rays or magnetic resonance imaging (MRI) of the affected joints. Although there is no lab test to diagnose psoriatic arthritis, your doctor may order tests on blood or joint fluid to rule out other forms of arthritis with ...

  14. Infectious Arthritis

    MedlinePlus

    ... Another form of reactive arthritis starts with eating food or handling something that has bacteria on it. To diagnose infectious arthritis, your health care provider may do tests of your blood, urine, and joint fluid. Treatment includes medicines and sometimes surgery.

  15. Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts

    SciTech Connect

    Sandler, Charlotta; Joutsiniemi, Saima; Lindstedt, Ken A.; Juutilainen, Timo; Kovanen, Petri T.; Eklund, Kari K. . E-mail: kari.eklund@hus.fi

    2006-08-18

    Synovial fibroblast is the key cell type in the growth of the pathological synovial tissue in arthritis. Here, we show that platelet-derived growth factor (PDGF) is a potent mitogen for synovial fibroblasts isolated from patients with rheumatoid arthritis. Inhibition of PDGF-receptor signalling by imatinib mesylate (1 {mu}M) completely abrogated the PDGF-stimulated proliferation and inhibited approximately 70% of serum-stimulated proliferation of synovial fibroblasts. Similar extent of inhibition was observed when PDGF was neutralized with anti-PDGF antibodies, suggesting that imatinib mesylate does not inhibit pathways other than those mediated by PDGF-receptors. No signs of apoptosis were detected in synovial fibroblasts cultured in the presence of imatinib. These results suggest that imatinib mesylate specifically inhibits PDGF-stimulated proliferation of synovial fibroblasts, and that inhibition of PDGF-receptors could represent a feasible target for novel antirheumatic therapies.

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

    PubMed Central

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

    2012-01-01

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

  17. B Cell Lymphoma mimicking Rheumatoid Arthritis.

    PubMed

    Cosatti, M A; Pisoni, C N; Altuve, J L; Lorente, C

    2016-01-01

    Non Hodking´s lymphoma (NHL) may involve bones but synovial involvement is uncommon. We describe a patient who presented with polyarthritis, sicca symptoms and rash suggestive of rheumatoid arthritis. An atypical skin rash prompted skin and synovial biopsies. A diagnosis of synovial and skin malignant large B-cell lymphoma anaplastic subtype was performed. Chemotherapy with dexamethasone, vincristine and rituximab was started. Following treatment the patient had complete resolution of cutaneous and articular lymphoma manifestations. PMID:27419896

  18. Acute pseudoseptic arthritis and palmoplantar pustulosis.

    PubMed

    Chamot, A M; Vion, B; Gerster, J C

    1986-01-01

    The case of a 60-year-old woman who developed acute peripheral arthritis of a pseudoseptic character (high synovial leucocytosis and fever) associated to a palmoplantar pustulosis is reported. PMID:3514079

  19. Minimal physiologically-based pharmacokinetic (mPBPK) model for a monoclonal antibody against interleukin-6 in mice with collagen-induced arthritis.

    PubMed

    Chen, Xi; Jiang, Xiling; Jusko, William J; Zhou, Honghui; Wang, Weirong

    2016-06-01

    Therapeutic monoclonal antibodies (mAb) targeting soluble inflammatory cytokines exert their pharmacological effects in rheumatoid arthritis through binding and neutralizing free cytokines in target tissue sites. Therefore suppression of free cytokines in such sites directly relates to the magnitude of therapeutic response. Although the interrelationships between mAb and cytokines have been examined in the systemic circulation, less is known about the interaction of mAb and cytokines in inflamed joints. In the present study, the interplay between the mAb, CNTO 345, and its target IL-6 in serum as well as ankle joint synovial fluid were characterized in collagen-induced arthritic mice. A minimal physiologically-based pharmacokinetic model with target-mediated drug disposition (TMDD) features in serum and ankle joint synovial fluid was developed for the assessment of the TMDD dynamics of CNTO 345 and IL-6. Our model indicates that TMDD kinetics in ankle joints differ greatly from that in serum. The differences can be attributed to the limited tissue distribution of CNTO 345 in ankle joint synovial fluid, the significant rise of the IL-6 baseline in ankle joint synovial fluid in comparison with serum, and the relative time-scales of elimination rates between CNTO 345, free IL-6 and CNTO 345-IL-6 complex in serum and ankle joint synovial fluid. PMID:27119518

  20. High prevalence of Kingella kingae in joint fluid from children with septic arthritis revealed by the BACTEC blood culture system.

    PubMed Central

    Yagupsky, P; Dagan, R; Howard, C W; Einhorn, M; Kassis, I; Simu, A

    1992-01-01

    In an effort to improve detection of fastidious organisms, joint fluid aspirates of pediatric patients were inoculated into BACTEC 460 aerobic blood culture bottles, in addition to cultures on solid media. Culture records for the 1988 to 1991 period were reviewed to compare the performance of both methods for the recovery of pathogens. Overall, 216 children underwent a diagnostic joint tap, and 63 specimens grew significant organisms, including Kingella kingae in 14. While both methods were comparable for recovery of usual pathogens, with a single exception, K. kingae isolates were detected by the BACTEC system only. K. kingae appears to be a more common cause of septic arthritis in children than has been previously recognized. The BACTEC blood culture system enhances the recovery of K. kingae from joint fluid and improves bacteriologic diagnosis of pediatric septic arthritis. PMID:1583131

  1. A study on FoxP3 and Tregs in paired samples of peripheral blood and synovium in rheumatoid arthritis

    PubMed Central

    Shalini P., Usha; Debnath, Tanya; JVS, Vidyasagar; Kamaraju, Suguna R.; Kancherla, Ravindranath; Chelluri, Lakshmi K.

    2016-01-01

    There is an increasing evidence suggesting the role of fork head boxP3 (FoxP3) in the development and the regulation of CD4+CD25+ Treg cells. T-cell regulatory mechanisms in rheumatoid arthritis patients were evaluated by the contributing factors such as pro-inflammatory cytokines, circulating immune complexes, HLA DR expression, ligand binding biomarkers, FoxP3 expression in paired samples of peripheral blood (PB) and synovial fluid (SF). These cellular responses were further correlated with the humoral immune responses such as anti-cyclic citrullinated peptides IgG (CCP), circulating immune complex-c1q IgG (CIC), immunoglobulin G (IgG) and immunoglobulin M (IgM) of the rheumatoid arthritis factor (RAF). The results suggest a definitive role of Tregs in the homeostatic control because there is an increase in FoxP3 (37%) and HLA-DR (45%) expression in the synovial fluid as compared to PB. Furthermore, humoral responses as a downstream effector mechanism are positively correlated with the pathogenesis of rheumatoid arthritis (RA). A positive relationship exists between quantitative anti-CCP production and the expression of HLA-DR. The study relates an increased and pivotal role of B cell activation in the synovial fluid thereby permitting the need to ablate the targeted B cell immune responses. PMID:26862306

  2. A Case of Polyarticular Pasteurella multocida Septic Arthritis

    PubMed Central

    Nitoslawski, Sarah; McConnell, Todd M.; Semret, Makeda; Stein, Michael A.

    2016-01-01

    A 76-year-old man with a history of osteoarthritis presents with right leg erythema and inability to weight-bear and pain in his right shoulder. Synovial fluid cell count of the knee and shoulder showed abundant neutrophils, and cultures of the knee showed growth of Pasteurella multocida. The patient owned four cats with which he had frequent contact, but history and physical examination elicited no evidence of scratches or bites. This case highlights the invasive potential of Pasteurella multocida in an immunocompetent individual and its capacity to cause septic arthritis in the setting of frequent animal contact. PMID:27366169

  3. Mycoplasma alkalescens-induced arthritis in dairy calves.

    PubMed

    Bennett, R H; Jasper, D E

    1978-02-15

    Mycoplasma alkalescens was isolated from 6 of 7 synovial fluid samples taken by arthrocentesis from 3-week- to 4-month-old Holstein-Friesian calves with severe arthritis (tibiotarsal or carpal joints). Approximately 30 of 215 calves in the herd were affected. In one 6-week-old calf, M alkalescens was isolated from the liver, right tibiotarsal joint, right and left popliteal lymph nodes, and an exposed umbilical artery. Intraarticular inoculations of broth cultures of M alkalescens initially induced a febrile response and then severe fibrinopurulent arthritis. Intravenous inoculation of M alkalescens induced only a febrile response. The natural disease may have been a complication of umbilical exposure to M alkalescens, causing omphaloarteritis and subsequent arthritis. Before and during the arthritis problem, the umbilicus of newborn calves was dipped in an organic iodine product with 10% glycerin, marketed as a postmilking teat dip. After the cause of the arthritis was determined, the umbilicus of each newborn calf was treated with 7% tincture of iodine and no new cases of arthritis occurred. PMID:624670

  4. Tribocorrosive behaviour of commonly used temporomandibular implants in a synovial fluid-like environment: Ti-6Al-4V and CoCrMo

    NASA Astrophysics Data System (ADS)

    Royhman, D.; Yuan, J. C.; Shokuhfar, T.; Takoudis, C.; Sukotjo, C.; Mathew, M. T.

    2013-10-01

    The temporomandibular joint implant metal alloys, Ti6Al4V and CoCrMo, (n = 3/group) were tested under free-potential and potentiostatic conditions using a custom-made tribocorrosion apparatus. Sliding duration (1800 cycles), frequency (1.0 Hz) and load (16 N) mimicked the daily mastication process. Synovial-like fluid (bovine calf serum, pH = 7.6 at 37 °C) was used to simulate the in vivo environment. Changes in friction coefficient were monitored throughout the sliding process. Changes in surface topography, total weight loss and roughness values were calculated using scanning electron microscopy and white-light interferometry. Finally, statistical analyses were performed using paired t-tests to determine significance between regions within each metal type and also independent sample t-tests to determine statistical significance between metal alloy types. Ti6Al4V demonstrated a greater decrease of potential than CoCrMo, a higher weight loss from wear (Kw = 257.8 versus 2.62 µg p < 0.0001), a higher weight loss from corrosion (Kc = 17.44 versus 0.14 µg p < 0.0001) and a higher weight loss from the combined effects of wear and corrosion (Kwc = 275.28 versus 2.76 µg p < 0.0001). White-light interferometry measurements demonstrated a greater difference in surface roughness inside the wear region in Ti6Al4V than CoCrMo after the sliding (Ra = 323.80 versus 70.74 nm p < 0.0001). In conclusion, CoCrMo alloy shows superior anti-corrosive and biomechanical properties.

  5. Correlation of changes in pain intensity with synovial fluid adenosine triphosphate levels after treatment of patients with osteoarthritis of the knee with high-molecular-weight hyaluronic acid.

    PubMed

    Kumahashi, Nobuyuki; Naitou, Kohei; Nishi, Hideyuki; Oae, Kazunori; Watanabe, Yohei; Kuwata, Suguru; Ochi, Mitsuo; Ikeda, Mitsugu; Uchio, Yuji

    2011-06-01

    We sought to determine whether a clinical association exists between osteoarthritis (OA)-associated knee pain and adenosine triphosphate (ATP) levels in synovial fluid (SF). A total of 28 patients with 28 primary OA knees were included. They routinely received intra-articular injection of high-molecular-weight hyaluronic acid (HA) once weekly for 5 weeks (treated group). Eight patients without knee pain who had undergone an operation for anterior or posterior cruciate ligament reconstruction 2 years ago were also examined (control group). SF and blood ATP concentrations, total amount of ATP, total SF volume, and Visual Analogue Scale (VAS) scores in all patients were measured and we compared pre-treatment values with those 1 week after the final treatment. We evaluated the correlation of change in total ATP (ΔATP) and change in VAS score (ΔVAS), ΔVAS and change in SF volume (ΔSF), and ATP concentration in SF and blood. In the treated group, SF ATP concentration, total amount of ATP, SF volume, and VAS score were all significantly lower post-treatment than pre-treatment (p = 0.0005, 0.0003, 0.0022, and < 0.0001, respectively). In treated group, ΔVAS was significantly associated with ΔATP (r = 0.56, p = 0.0032), ΔSF was significantly associated with ΔVAS (r = 0.78, p < 0.0001), and total amount of SF ATP and SF volume at pre-treatment were significantly higher than the control group (p < 0.0001, p < 0.0001) We demonstrated an association between SF ATP level changes and OA knee pain, which should facilitate a further understanding of OA pain mechanisms. PMID:20627733

  6. 5. Diagnosis and Treatment of Lyme Arthritis

    PubMed Central

    Arvikar, Sheila L.; Steere, Allen C.

    2015-01-01

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

  7. Yersinia arthritis: a clinical, immunological, and family study of 2 cases.

    PubMed Central

    Sheldon, P J; Mair, N S; Fox, E

    1982-01-01

    We describe 2 patients who presented with yersinia arthritis within a period of 5 months in Leicester. Both were HLA B27 positive. Arthritis followed 2 to 3 weeks after pneumonia, abdominal pain, dysuria, and evidence of hepatic involvement in the first case, and dysuria and conjunctivitis in the second. Immunological studies showed the presence of IgM, IgG, and IgA antibodies at a significant level against Yersinia enterocolitica serotype O:3 in serum and synovial fluid, and immune complexes in the serum of the first case and synovial fluid of both. Arthropathy resolved after 16 weeks in the first case and 12 weeks in the second, the latter requiring systemic corticosteroids. Family studies revealed psoriatic spondylarthritis in the brother, and bilateral sacroiliitis in the mother of the second case. Both were HLA B27 positive. These are the fourth and fifth reported cases of yersinia arthritis in Britain. We believe the condition is probably underdiagnosed and that yersiniosis should be considered as a possibility in otherwise unexplained arthritis. PMID:6978685

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

    PubMed Central

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

    1980-01-01

    Experiments were designed to correlate morphologic lesions with the presence of caprine arthritis-encephalitis virus (CAEV). Twenty-one cesarean-derived goat kids were infected with 10(6) to 10(7) TCID50 of virus, killed sequentially, and examined for viral antigens by immunofluorescence, viral infectivity by isolation and titration, and morphologic changes by light microscopy. Fluorescent viral antigens were detected from 1 to 10 days postinoculation (DPI) and only in synovial cells. Virus was reisolated from several joints and from brain 0.5 to 79 DPI. Increases in synovial fluid cell counts were noted by 1 DPI, and morphologic changes in synovial membranes were present from 3 to 45 DPI. Joint lesions progressed from mild synovial cell hyperplasia and perivascular mononuclear cell infiltration to severe synovial cell hyperplasia and mononuclear cell infiltration with villous hypertrophy. Lesions elsewhere were mild, consisting only of perivascular mononuclear cell infiltrates. Eleven cesarean-derived control goats were negative for viral antigens, virus, and morphologic lesions. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:6990770

  9. Utility of synovial biopsy

    PubMed Central

    2009-01-01

    Synovial biopsies, gained either by blind needle biopsy or minimally invasive arthroscopy, offer additional information in certain clinical situations where routine assessment has not permitted a certain diagnosis. In research settings, synovial histology and modern applications of molecular biology increase our insight into pathogenesis and enable responses to treatment with new therapeutic agents to be assessed directly at the pathophysiological level. This review focuses on the diagnostic usefulness of synovial biopsies in the light of actual developments. PMID:19951395

  10. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis.

    PubMed

    Kurowska-Stolarska, Mariola; Alivernini, Stefano; Ballantine, Lucy E; Asquith, Darren L; Millar, Neal L; Gilchrist, Derek S; Reilly, James; Ierna, Michelle; Fraser, Alasdair R; Stolarski, Bartosz; McSharry, Charles; Hueber, Axel J; Baxter, Derek; Hunter, John; Gay, Steffen; Liew, Foo Y; McInnes, Iain B

    2011-07-01

    MicroRNA (miRNA) species (miR) regulate mRNA translation and are implicated as mediators of disease pathology via coordinated regulation of molecular effector pathways. Unraveling miR disease-related activities will facilitate future therapeutic interventions. miR-155 recently has been identified with critical immune regulatory functions. Although detected in articular tissues, the functional role of miR-155 in inflammatory arthritis has not been defined. We report here that miR-155 is up-regulated in synovial membrane and synovial fluid (SF) macrophages from patients with rheumatoid arthritis (RA). The increased expression of miR-155 in SF CD14(+) cells was associated with lower expression of the miR-155 target, Src homology 2-containing inositol phosphatase-1 (SHIP-1), an inhibitor of inflammation. Similarly, SHIP-1 expression was decreased in CD68(+) cells in the synovial lining layer in RA patients as compared with osteoarthritis patients. Overexpression of miR-155 in PB CD14(+) cells led to down-regulation of SHIP-1 and an increase in the production of proinflammatory cytokines. Conversely, inhibition of miR-155 in RA synovial CD14(+) cells reduced TNF-α production. Finally, miR-155-deficient mice are resistant to collagen-induced arthritis, with profound suppression of antigen-specific Th17 cell and autoantibody responses and markedly reduced articular inflammation. Our data therefore identify a role of miR-155 in clinical and experimental arthritis and suggest that miR-155 may be an intriguing therapeutic target. PMID:21690378

  11. [Immunomorphological characteristics of the synovial membrane in rheumatic diseases].

    PubMed

    Radenska-Lopovok, S G

    2016-01-01

    The synovial membrane is frequently a target in rheumatic diseases. A search for diagnostic criteria and determination of changes in the pathological process necessitate standardized biopsy diagnostic techniques and quantification of morphological changes using digital imaging methods. The paper considers main methods for obtaining synovial membrane samples. It presents major morphological and immunohistochemical variations in synovitis in the presence of rheumatoid arthritis, ankylosing spondylitis, and osteoarthrosis. It shows different immunological and autoinflammatory mechanisms of these diseases. Synovial membrane inflammation in rheumatoid arthritis, ankylosing spondylitis, and osteoarthrosis is characterized by different components of morphogenesis, which is proven by the expression of different cell markers. Rheumatoid synovitis is an autoinflammatory process; synovitis in ankylosing spondylitis is characterized by autoinflammatory processes; biomechanical factors as joint inflammation triggers are leading in osteoarthrosis. PMID:27600785

  12. Mesenchymal Stem Cells Obtained from Synovial Fluid Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells on a Matrigel Coating Exhibited Enhanced Proliferation and Differentiation Potential

    PubMed Central

    Zhang, Hong; Liu, Wen-Jing; Jiang, Rui; Li, Wen-Yu; Zheng, You-Hua; Zhang, Zhi-Guang

    2015-01-01

    Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) serve as a promising source for cell-based therapies in regenerative medicine. However, optimal methods for transforming iPSCs into MSCs and the characteristics of iPSC-MSCs obtained from different methods remain poorly understood. In this study, we developed a one-step method for obtaining iPSC-MSCs (CD146+STRO-1+ MSCs) from human synovial fluid MSC-derived induced iPSCs (SFMSC-iPSCs). CD146-STRO-1-SFMSCs were reprogrammed into iPSCs by transduction with lentivirus-mediated Sox2, Oct-3/4, klf4, and c-Myc. SFMSC-iPSCs were maintained with mTeSR1 medium in Matrigel-coated culture plates. Single dissociated cells were obtained by digesting the SFMSC-iPSCs with trypsin. The dissociated cells were then plated into Matrigel-coated culture plate with alpha minimum essential medium supplemented with 10% fetal bovine serum, 1× Glutamax, and the ROCK inhibitor Y-27632. Cells were then passaged in standard cell culture plates with alpha minimum essential medium supplemented with 10% fetal bovine serum and 1× Glutamax. After passaging in vitro, the cells showed a homogenous spindle-shape similar to their ancestor cells (SFMSCs), but with more robust proliferative activity. Flow cytometric analysis revealed typical MSC surface markers, including expression of CD73, CD90, CD105, and CD44 and lack of CD45, CD34, CD11b, CD19, and HLA-DR. However, these cells were positive for CD146 and stro-1, which the ancestor cells were not. Moreover, the cells could also be induced to differentiate in osteogenic, chondrogenic, and adipogenic lineages in vitro. The differentiation potential was improved compared with the ancestor cells in vitro. The cells were not found to exhibit oncogenicity in vivo. Therefore, the method presented herein facilitated the generation of STRO-1+CD146+ MSCs from SFMSC-iPSCs exhibiting enhanced proliferation and differentiation potential. PMID:26649753

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

    PubMed

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

    2015-06-01

    Mycoplasmas, including Ureaplasma and Mycoplasma species, are uncommon but important causes of septic arthritis, especially affecting immunosuppressed patients. Many of the reported cases have been associated with congenital immunodeficiency disorders, especially hypogammaglobulinemia. Mycoplasmas are difficult to grow in the laboratory, and these infections may be underdiagnosed using culture techniques. We report a case of a 21-year-old woman with juvenile idiopathic arthritis and hip arthroplasties treated with rituximab and adalimumab who developed urogenital infections and soft tissue abscesses followed by knee arthritis with negative routine cultures. Ureaplasma species was identified from synovial fluid on 2 separate occasions using a broad-range 16S ribosomal RNA gene polymerase chain reaction. Azithromycin led to rapid improvement in symptoms, but after completion of therapy, involvement of the hip prosthesis became apparent, and again, 16S rRNA gene polymerase chain reaction was positive for Ureaplasma species. The literature is reviewed with a discussion of risk factors for Mycoplasma septic arthritis, clinical presentation, methods of diagnosis, and treatment. PMID:26010188

  14. Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications.

    PubMed Central

    Colville-Nash, P R; Scott, D L

    1992-01-01

    Rheumatoid arthritis can be considered as one of the family of 'angiogenesis dependent diseases'. Angiogenesis in rheumatoid arthritis is controlled by a variety of factors found in the synovial fluid and pannus tissue. Modulation of the angiogenic component of the disease may alter the pathogenesis of the condition, and subsequent cartilage and joint destruction, by reducing the area of the endothelium in the pannus and restricting pannus growth. Current therapeutic strategies exert, to varying extents, an inhibitory effect on the angiogenic process. In particular, the mode of action of the slow acting antirheumatic drugs may be due to their effect on the angiogenic response. The development of novel angiostatic treatments for chronic inflammatory joint disease may lead to a new therapeutic approach in controlling disease progression. PMID:1378718

  15. Deficient cytokine control modulates temporomandibular joint pain in rheumatoid arthritis.

    PubMed

    Ahmed, Neveen; Catrina, Anca I; Alyamani, Ahmed O; Mustafa, Hamid; Alstergren, Per

    2015-08-01

    The aim was to investigate how endogenous cytokine control of tumor necrosis factor (TNF) influences temporomandibular joint (TMJ) pain in relation to the role of anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA). Twenty-six consecutive patients with TMJ RA were included. Temporomandibular joint pain intensity was assessed at rest, on maximum mouth opening, on chewing, and on palpation. Mandibular movement capacity and degree of anterior open bite (a clinical sign of structural destruction of TMJ tissues) were also assessed. Systemic inflammatory activity was assessed using the Disease Activity Score in 28 joints (DAS28) for rheumatoid arthritis. Samples of TMJ synovial fluid and blood were obtained and analyzed for TNF, its soluble receptor, soluble TNF receptor II (TNFsRII), and ACPA. A high concentration of TNF in relation to the concentration of TNFsRII in TMJ synovial fluid was associated with TMJ pain on posterior palpation on maximum mouth opening. The ACPA concentration correlated significantly to the TNF concentration, but not to the TNFsRII concentration, indicating that increased inflammatory activity is mainly caused by an insufficient increase in anti-inflammatory mediators. This study indicates that TMJ pain on palpation in patients with RA is related to a deficiency in local cytokine control that contributes to increased inflammatory activity, including sensitization to mechanical stimuli over the TMJ. PMID:26010823

  16. Extradural spinal synovial cysts in nine dogs.

    PubMed

    Dickinson, P J; Sturges, B K; Berry, W L; Vernau, K M; Koblik, P D; Lecouteur, R A

    2001-10-01

    Nine dogs presenting for investigation of cervical or thoracolumbar myelopathies were diagnosed with extradural spinal synovial cysts. Degenerative disease affecting the articular facets or intervertebral discs was present on plain spinal radiographs in all cases. Myelography was consistent with dorsolateral, extradural spinal cord compression. Two groups of dogs were identified: (1) young, giant breed dogs with multiple cysts involving one or more levels of the cervical spinal cord; and (2) older, large breed dogs with solitary cysts involving the thoracolumbar spinal cord. The synovial cysts constituted the major compressive lesions in four of the dogs. Analysis of lumbar cerebrospinal fluid demonstrated albuminocytological dissociation, consistent with chronic compressive myelopathy, in six dogs. All dogs underwent decompressive surgery and the diagnosis of synovial cysts was confirmed histologically. The mean follow-up period was 17 months (range four to 36 months). At the time of follow-up, all dogs were fully ambulatory with improved neurological function compared with that at initial presentation. PMID:11688527

  17. Melorheostosis mimicking synovial osteochondromatosis.

    PubMed

    Wadhwa, Vibhor; Chhabra, Avneesh; Samet, Jonathan D

    2014-01-01

    Melorheostosis is an uncommon, sporadic, sclerosing bone lesion that may affect the adjacent soft tissues. It has been associated with many entities such as osteopoikilosis, soft tissue vascular malformations, bone and soft tissue tumors, nephrotic syndrome, segmental limb contractures, osteosarcoma, desmoid tumor, and mesenteric fibromatosis. Synovial osteochondromatosis is a benign neoplasia of the hyaline cartilage presenting as nodules in the subsynovial tissue of a joint or tendon sheath. The intra-articular extension of melorheostosis mimicking synovial osteochondromatosis has not been reported before. In this article, the authors describe an unusual case mimicking synovial chondromatosis arising as a result of melorheostosis and their characteristic imaging findings. PMID:25971832

  18. Septic Arthritis in the Temporomandibular Joint

    PubMed Central

    Al-Khalisy, Hassan Mahdi; Nikiforov, Ivan; Mansoora, Qurat; Goldman, John; Cheriyath, Pramil

    2015-01-01

    Septic arthritis of the temporomandibular joint (TMJ) is a rare event that has only been reported a few dozen times worldwide. This case is remarkable for septic arthritis of the TMJ joint in an otherwise healthy male. Case Report: A 24-year-old male presented to the emergency department with periauricular swelling, erythema, fever, myalgia's and generalized joint pain. He had previously sought medical attention and was placed on ciprofloxacin. However, he developed facial swelling and a rash and had to discontinue the antibiotic. On physical exam the patient had a large swelling and tenderness in his left periauricular area, with erythema and deviation of the right mandible which limited his ability to open the mouth. A computed tomography showed mild asymmetric soft tissue swelling in the left pharyngeal region but did not show joint effusion. Subsequent magnetic resonance imaging did show effusion of the joint space. The effusion was drained, and the synovial fluid was submitted for gram stain, culture, and sensitivity. The cultures grew menthicillin sensitive Staphyloccocus Aureus. The patient was discharged to complete a two week course of intravenous (IV) Ceftriaxone and IV Vancomycin via home infusion. Conclusion: Septic Arthritis of the TMJ is a rare event with very specific clinical symptoms. Due to the low sensitivity of the computed tomography scan, magnetic resonance imaging should be considered when computed tomography scan is negative for TMJ effusion. PMID:26713295

  19. Arthroscopic Management of Synovial Osteochondromatosis of the Hip.

    PubMed

    Blitzer, Charles M; Scarano, Kyle A

    2015-06-01

    Synovial osteochondromatosis is a benign metaplasia of the synovium resulting in the formation of osteocartilaginous nodules within the synovial lining. At presentation, radiographs typically reveal these nodules to have broken free from the synovial lining, becoming loose bodies residing in the free space of the affected joint. These fragments readily receive the necessary nutrients for continued growth from the synovial fluid in which they reside. Controversy exists over the management of the disease. Some physicians call for arthrotomy with a complete synovectomy, whereas others vouch for a minimally invasive arthroscopic approach. In the case described here, the surgeon decided on hip arthroscopy to treat synovial osteochondromatosis in a 61-year-old woman. All but one loose body that was adherent in the anterior hip capsule was successfully removed and the patient recovered promptly. This case highlights the importance of hip arthroscopy and its usefulness not only in treating conditions such as synovial osteochondromatosis, but also in accurately diagnosing them. Recognition and management of hip conditions such as synovial osteochondromatosis through arthroscopy result in minimally invasive treatment and decreased morbidity and may markedly accelerate patient rehabilitation. It is the authors' belief that this unique case further suggests the practicality of using hip arthroscopy to successfully treat synovial osteochondromatosis. PMID:26091229

  20. Intra-Articular Fms-Like Tyrosine Kinase 3 Ligand Expression Is a Driving Force in Induction and Progression of Arthritis

    PubMed Central

    Dehlin, Mats; Bokarewa, Maria; Rottapel, Robert; Foster, Simon J.; Magnusson, Mattias; Dahlberg, Leif E.; Tarkowski, Andrej

    2008-01-01

    Background One of the hallmarks of rheumatoid arthritis (RA) is hyperplasia and inflammation of the synovial tissue being characterized by in situ occurrence of highly differentiated leukocytes. Fms-like tyrosine kinase 3 (Flt3) has a crucial role in hematopoiesis, regulation of cell proliferation, differentiation and apoptosis. Typically, Flt3 is expressed on early myeloid and lymphoid progenitors and is activated by its soluble ligand (Flt3-L). The highly differentiated cellular pattern in the synovium of the RA patients made us hypothesize that Flt3-L, with its ability to induce proliferation and differentiation, could be of importance in induction and/or progression of arthritis. Methodology/Principal Findings To investigate occurrence of Flt3-L in RA we have measured its levels in matched serum and synovial fluid samples from 130 patients and 107 controls. To analyse the pro-inflammatory role of Flt3-L, we continuously overexpressed this protein locally in healthy mouse joints using homologous B-cell line transfected with Flt3-L gene. Additionally, recombinant Flt3-L was instillated intra-articularly in combination with peptidoglycans, a Toll Like Receptor 2-ligand with stong arthritogenic properties. Our results show significantly higher levels of Flt3-L in the synovial fluid as compared to serum levels in RA subjects (p = 0.0001). In addition, RA synovial fluid levels of Flt-3-L were significantly higher than these obtained from synovial fluids originating from non-inflammatory joint diseases (p = 0.022). Intra-articular administration of B-cell line transfected with Flt3-L gene resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and only in a minority of cases caused synovial proliferation! Flt3-ligand potentiated peptidoglycan induced arthritis as compared to mice injected with peptidoglycan alone (p<0.05). Conclusions/Significance Our findings indicate that Flt3

  1. Characterization of IL-7 and IL-7R in the pathogenesis of Rheumatoid Arthritis

    PubMed Central

    Pickens, Sarah R.; Chamberlain, Nathan D.; Volin, Michael V.; Pope, Richard M.; Talarico, Nicholas E; Mandelin, Arthur M.; Shahrara, Shiva

    2012-01-01

    Objective The aim of the study was to characterize the expression of IL-7 and IL-7R in rheumatoid arthritis (RA) synovial tissue and to examine their regulation and pathogenic role in macrophages, endothelial cells and RA synovial tissue fibroblasts. Methods Expression of IL-7 and IL-7R was demonstrated in RA and normal synovial tissues employing immunohistochemistry. Expression and regulation of IL-7 and IL-7R was determined in RA peripheral blood in vitro differentiated macrophages, RA synovial tissue fibroblasts and human microvascular endothelial cells (HMVECs) by real-time RT-PCR and/or flow cytometry. Next, IL-7 activated macrophages, RA fibroblasts and endothelial cells were examined for production of proangiogenic factors employing ELISA. Results IL-7 and IL-7R were coexpressed on RA synovial tissue lining and sublining macrophages and endothelial cells. Consistently, expression of IL-7 and its receptor were significantly elevated in RA synovial fluid and peripheral blood macrophages as well as RA fibroblasts compared to normal cells. TLR4 ligation and stimulation with TNF-α modulated expression of IL-7 and IL-7R on RA macrophages and HMVECs. However, in RA fibroblasts only expression of IL-7R was increased by LPS and TNF-α activation. IL-7 also mediated RA pathogenesis by inducing production of potent proangiogenic factors from macrophages and endothelial cells. Conclusion We identify, for the first time, regulators of IL-7 and IL-7R expression in RA fibroblasts, RA peripheral blood in vitro differentiated macrophages and endothelial cells and we document a novel role of IL-7 in RA angiogenesis. PMID:21647866

  2. Brucella arthritis of the knee, 1 year after revision of anterior cruciate ligament reconstruction.

    PubMed

    Papastergiou, S G; Koukoulias, N E; Koumis, P; Kyparlis, D; Santas, R

    2011-01-01

    Brucellosis is a zoonotic infection with a broad spectrum of clinical manifestations. The authors report the first case in the literature of septic arthritis of the knee 1 year after revision of anterior cruciate ligament reconstruction. Brucella melitensis biotype 3 was found in both synovial fluid and blood cultures. The patient was treated initially with arthroscopic debridement. After the diagnosis was confirmed, a second arthroscopic lavage and metal work removal was applied leaving the graft in place. Antimicrobial chemotherapy was prescribed for 3 months. The infection was fully eradicated and the patient is still asymptomatic, 4 years after the treatment. PMID:22700607

  3. Brucella arthritis of the knee, 1 year after revision of anterior cruciate ligament reconstruction

    PubMed Central

    Papastergiou, S G; Koukoulias, N E; Koumis, P; Kyparlis, D; Santas, R

    2011-01-01

    Brucellosis is a zoonotic infection with a broad spectrum of clinical manifestations. The authors report the first case in the literature of septic arthritis of the knee 1 year after revision of anterior cruciate ligament reconstruction. Brucella melitensis biotype 3 was found in both synovial fluid and blood cultures. The patient was treated initially with arthroscopic debridement. After the diagnosis was confirmed, a second arthroscopic lavage and metal work removal was applied leaving the graft in place. Antimicrobial chemotherapy was prescribed for 3 months. The infection was fully eradicated and the patient is still asymptomatic, 4 years after the treatment. PMID:22700607

  4. Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis – a prospective cohort study

    PubMed Central

    2014-01-01

    Introduction Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA). Methods In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for six months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analysed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor). Results During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (P = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (P = 0.002). Conclusions Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse. PMID:24950951

  5. Chronic arthritis associated with the presence of intrasynovial rubella virus.

    PubMed Central

    Grahame, R; Armstrong, R; Simmons, N; Wilton, J M; Dyson, M; Laurent, R; Millis, R; Mims, C A

    1983-01-01

    In this report we present 21 instances in which live rubella virus was isolated from synovial fluid obtained from 6 cases of inflammatory oligoarthritis or polyarthritis over a period of 2 years in the absence of firm clinical evidence of rubella. In 3 cases (cases 1, 2, 6,) a persistent oligoarthritis predominantly affecting the knee joints occurred in 2 adult women and one man, lasting to date 27, 29, and 18 months respectively, and in one of these cases virions were found in cells of the synovial membrane. In case 3 a boy of 9 presented with an illness indistinguishable from the systemic variety of juvenile chronic arthritis (Still's disease). In case 4 a young man with persistent monoarthritis was found to have ankylosing spondylitis, and in case 5 a progressive erosive polyarthritis developed 5 years after an attack of rubella complicated by rubella arthritis. The virus was identified by a variety of virological techniques and infection confirmed by immunofluorescence and (in one case) electron microscopy. Images PMID:6830322

  6. Targeting the coagulation factor fibrinogen for arthritis therapy.

    PubMed

    Raghu, Harini; Flick, Matthew J

    2011-09-01

    Fibrinogen is a provisional matrix protein of the coagulation system that following proteolytic cleavage by the protease thrombin polymerizes to form fibrin, the structural basis of the blood clot. Fibrin polymer formation at sites of vessel injury is critical to normal hemostasis. However, fibrin deposition within damaged tissues is also a common pathological feature of inflammatory diseases, including rheumatoid arthritis. Fibrin deposition has been readily detected along articular surfaces, within inflamed hyperplastic synovial tissue, and as a component of insoluble "rice bodies" within the synovial fluid of arthritic joints. Recent data has suggested that fibrin deposition within inflamed tissues is not simply a reflection of a disease process but rather actively contributes to disease pathogenesis. One mechanism that has been demonstrated to directly link fibrin(ogen) to the regulation of inflammation is the ability of fibrin(ogen) to serve as a ligand for cell-surface receptors, particularly integrins. Indeed, engagement of fibrin(ogen) by the leukocyte integrin receptor αMβ2 appears to be a common and fundamental event driving local inflammation. Recent studies have demonstrated that eliminating fibrin(ogen)-αMβ2 interactions can significantly limit the progression of multiple inflammatory diseases, including arthritis, without compromising the ability of fibrinogen to function in coagulation. These exciting findings have opened the door to new opportunities for targeting fibrinogen as an inflammatory mediator while leaving intact its hemostatic properties. PMID:21401516

  7. Synovial lipomatosis: A rare cause of knee pain in an adolescent female

    PubMed Central

    Miladore, Nicholas; Childs, Mary A; Sabesan, Vani J

    2015-01-01

    Synovial lipomatosis is a benign proliferative disease of the subsynovial adipose which can lead to a variety of presentations. Cases of synovial lipomatosis in children or adolescents are rare. This case report describes an adolescent patient with a rare bilateral presentation of synovial lipomatosis. She had been treated for years prior to her presentation for juvenile idiopathic arthritis. She presented with chronic bilateral knee pain, swelling, and mechanical symptoms. Bilateral MR imaging demonstrated effusions, hypertrophy of the synovium, and polyp-like projections of tissue with the same signal intensity as fat which is pathognomonic for synovial lipomatosis. Arthroscopic synovectomy and extensive debridement of polyp like fat projections of the right knee was performed. Histopathology was consistent with the synovial lipomatosis diagnosis. Postoperatively, the patient was satisfied with her outcome with improved pain relief and function in her right knee. PMID:25893181

  8. Arthritis - resources

    MedlinePlus

    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. ...

  9. Anti-inflammatory effects of intravenous methotrexate associated with lipid nanoemulsions on antigen-induced arthritis

    PubMed Central

    Mello, Suzana B V; Tavares, Elaine R; Guido, Maria Carolina; Bonfá, Eloisa; Maranhão, Raul C

    2016-01-01

    OBJECTIVE: To test the hypothesis that intravenous use of methotrexate associated with lipid nanoemulsions can achieve superior anti-inflammatory effects in the joints of rabbits with antigen-induced arthritis compared with commercial methotrexate. METHODS: Arthritis was induced in New Zealand rabbits sensitized with methylated bovine serum albumin and subsequently intra-articularly injected with the antigen. A nanoemulsion of methotrexate labeled with 3H-cholesteryl ether (4 mg/kg methotrexate) was then intravenously injected into four rabbits to determine the plasma decaying curves and the biodistribution of the methotrexate nanoemulsion by radioactive counting. Additionally, the pharmacokinetics of the methotrexate nanoemulsion were determined by high-pressure liquid chromatography. Twenty-four hours after arthritis induction, the animals were allocated into three groups, with intravenous injection with saline solution (n=9), methotrexate nanoemulsion (0.5 µmol/kg methotrexate, n=7), or commercial methotrexate (0.5 µmol/kg, n=4). The rabbits were sacrificed 24 h afterward. Synovial fluid was then collected for protein leakage and cell content analyses and synovial membranes were collected for histopathological analysis. RESULTS: The methotrexate nanoemulsion was taken up mainly by the liver and the uptake by arthritic joints was two-fold greater than that by control joints. The methotrexate nanoemulsion treatment reduced leukocyte influx into the synovial fluid by nearly 65%; in particular, mononuclear and polymorphonuclear cells were reduced by 47 and 72%, respectively. In contrast, cell influx was unaffected following treatment with commercial methotrexate. Protein leakage into the arthritic knees of the rabbits was also more limited following methotrexate nanoemulsion treatment than following commercial methotrexate treatment. CONCLUSIONS: The intravenous methotrexate nanoemulsion showed anti-inflammatory effects on the synovia of arthritic joints that were

  10. Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study

    PubMed Central

    Zheng, Guifeng; Zou, Hai; Wang, Jian Min; Lin, Yao Yao; Chuka, Chifundo Martha; Ge, Ren Shan; Zhai, Weitao; Wang, Jian Guang

    2015-01-01

    Objectives To explore the pathogenesis of rheumatoid arthritis (RA), the different metabolites were screened in synovial fluid by metabolomics. Methods Synovial fluid from 25 RA patients and 10 normal subjects were analyzed by GC/TOF MS analysis so as to give a broad overview of synovial fluid metabolites. The metabolic profiles of RA patients and normal subjects were compared using multivariate statistical analysis. Different proteins were verified by qPCR and western blot. Different metabolites were verified by colorimetric assay kit in 25 inactive RA patients, 25 active RA patients and 20 normal subjects. The influence of hypoxia-inducible factor (HIF)-1α pathway on catabolism was detected by HIF-1α knockdown. Results A subset of 58 metabolites was identified, in which the concentrations of 7 metabolites related to energy metabolism were significantly different as shown by importance in the projection (VIP) (VIP≥1) and Student’s t-test (p<0.05). In the 7 metabolites, the concentration of glucose was decreased, and the concentration of lactic acid was increased in the synovial fluid of RA patients than normal subjects verified by colorimetric assay Kit. Receiver operator characteristic (ROC) analysis shows that the concentration of glucose and lactic acid in synovial fluid could be used as dependable biomarkers for the diagnosis of active RA, provided an AUC of 0.906 and 0.922. Sensitivity and specificity, which were determined by cut-off points, reached 84% and 96% in sensitivity and 95% and 85% in specificity, respectively. The verification of different proteins identified in our previous proteomic study shows that the enzymes of anaerobic catabolism were up-regulated (PFKP and LDHA), and the enzymes of aerobic oxidation and fatty acid oxidation were down-regulated (CS, DLST, PGD, ACSL4, ACADVL and HADHA) in RA patients. The expression of HIF-1α and the enzymes of aerobic oxidation and fatty acid oxidation were decreased and the enzymes of anaerobic

  11. Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

    PubMed Central

    Norling, Lucy V.; Headland, Sarah E.; Dalli, Jesmond; Arnardottir, Hildur H.; Haworth, Oliver; Jones, Hefin R.; Irimia, Daniel; Serhan, Charles N.; Perretti, Mauro

    2016-01-01

    Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which — once applied to human neutrophils — attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor–deficient mice termed ALX/fpr2/3−/−. These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA. PMID:27158677

  12. Immunopathology of chronic lentivirus-induced arthritis.

    PubMed Central

    Wilkerson, M. J.; Davis, W. C.; Baszler, T. V.; Cheevers, W. P.

    1995-01-01

    This study evaluated histopathology and mononuclear cell phenotypes in synovial lesions of chronic arthritis induced by experimental infection of Saanen goats with caprine arthritis-encephalitis lentivirus. Histological examination of carpal joint synovium of three infected goats with clinical arthritis revealed progressive lesions consisting of membrane villus hypertrophy with extensive angiogenesis and mononuclear cell infiltration and degenerative changes of membrane villus necrosis associated with loss of vasculature and infiltrates. Changes in synovial tissue of five age-matched infected goats without clinical arthritis were limited to moderate synovial membrane hyperplasia also noted in an age-matched uninfected goat. Immunohistochemistry identified CD45R+ CD5- B lymphocytes as the principal component of most perivascular infiltrates in arthritic synovium. Other mononuclear cells included perivascular CD4+ and CD8+ T lymphocytes and macrophages with a prominent accumulation of CD8+ T lymphocytes at the lining surface of inflamed villi. T lymphocytes and macrophages as well as synovial lining cells were activated with respect to MHC class II but not for interleukin-2 receptors. Inflamed villi also contained lymphoid aggregates comprised of B cell germinal centers and activated T-cell mantles. B cells expressing immunoglobulin occurred around follicles and throughout inflamed villi. These findings indicate that memory immune responses that favor expansion and maturation of B cells and immunoglobulin production contribute to the immunopathology of chronic arthritis. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 PMID:7778682

  13. Synovial sarcoma: laryngopharynx a challenge.

    PubMed

    Verma, Ravinder; Verma, Ravneet Ravinder; Verma, Rohan Ravinder; Sardana, N K

    2014-06-01

    Synovial sarcoma is a rare malignant tumor. It derives from a mesenchymal precursor stem cell that is unrelated to mature synovial tissue. Synovial sarcoma classically affects lower limbs between the ages of 15 and 40 years and the proportion of male-to-female patients is 3:2. It is very rare in the head and neck region especially in laryngopharynx. Till date, only six cases of synovial sarcoma involving laryngopharynx have been reported in the English literature. Painless mass, hoarseness, upper respiratory distress, and dysphagia characterize the original complaints in laryngopharyngeal synovial sarcoma. Because head and neck synovial sarcoma in clinical practice is so uncommon, early diagnosis is difficult and the treatment protocol is unclear. Therefore, every case report should include complete information on presentation and management. Also, long-term prognostic indices need to be evaluated. We hereby report a case of large laryngopharyngeal synovial sarcoma confirmed by histopathology and immunohistochemistry with review of literature. PMID:24822167

  14. Primary Intracranial Synovial Sarcoma.

    PubMed

    Patel, Mohit; Li, Luyuan; Nguyen, Ha Son; Doan, Ninh; Sinson, Grant; Mueller, Wade

    2016-01-01

    Background. Synovial sarcoma is an aggressive soft tissue sarcoma with uncertain histological origin. The pathology frequently presents as a localized disease, especially near large joints around the knee and thigh. Intracranial disease, which is rare, has been reported as metastasis from synovial sarcoma. We report a case with no obvious primary extracranial pathology, suggesting primary intracranial disease; this has not been reported in the literature. Case Description. A 21-year-old male, with a prior right skull lesion resection for atypical spindle cell neoplasm, presented with headaches, gait instability, left arm weakness, and left homonymous hemianopsia. CT of head demonstrated a right parietal hemorrhagic lesion with mass effect, requiring surgical decompression. Histopathology revealed synovial sarcoma. FISH analysis noted the existence of the t(X;18)(p11.2;q11.2) chromosomal translocation. PET scan did not show other metastatic disease. He underwent stereotactic radiotherapy and adjuvant chemotherapy. At 2-year follow-up, he remained nonfocal without recurrence. Conclusion. We report the first known case of primary intracranial synovial sarcoma. Moreover, we stress that intracranial lesions may have a tendency for hemorrhage, requiring urgent lifesaving decompression. PMID:27247811

  15. Primary Intracranial Synovial Sarcoma

    PubMed Central

    Li, Luyuan; Sinson, Grant; Mueller, Wade

    2016-01-01

    Background. Synovial sarcoma is an aggressive soft tissue sarcoma with uncertain histological origin. The pathology frequently presents as a localized disease, especially near large joints around the knee and thigh. Intracranial disease, which is rare, has been reported as metastasis from synovial sarcoma. We report a case with no obvious primary extracranial pathology, suggesting primary intracranial disease; this has not been reported in the literature. Case Description. A 21-year-old male, with a prior right skull lesion resection for atypical spindle cell neoplasm, presented with headaches, gait instability, left arm weakness, and left homonymous hemianopsia. CT of head demonstrated a right parietal hemorrhagic lesion with mass effect, requiring surgical decompression. Histopathology revealed synovial sarcoma. FISH analysis noted the existence of the t(X;18)(p11.2;q11.2) chromosomal translocation. PET scan did not show other metastatic disease. He underwent stereotactic radiotherapy and adjuvant chemotherapy. At 2-year follow-up, he remained nonfocal without recurrence. Conclusion. We report the first known case of primary intracranial synovial sarcoma. Moreover, we stress that intracranial lesions may have a tendency for hemorrhage, requiring urgent lifesaving decompression. PMID:27247811

  16. Borrelia burgdorferi migrates into joint capsules and causes an up-regulation of interleukin-8 in synovial membranes of dogs experimentally infected with ticks.

    PubMed Central

    Straubinger, R K; Straubinger, A F; Härter, L; Jacobson, R H; Chang, Y F; Summers, B A; Erb, H N; Appel, M J

    1997-01-01

    . Histologically, nonsuppurative arthritis was found in multiple joints, and mild to moderate cortical hyperplasia was found in draining lymph nodes. Five uninfected dogs without lameness (group C) had normal synovial fluids and tissues. In all infected dogs, live spirochetes were demonstrated more frequently in tissues of the somatic quadrant closest to the tick bite than in tissues further from the site of infection, suggesting that dissemination of B. burgdorferi occurs more by migration than by blood-borne spread. From these studies employing a canine model of B. burgdorferi infection, we conclude that IL-8 is involved in the pathogenesis of acute Lyme arthritis. PMID:9119462

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

    PubMed Central

    Kou, Y.-Y.; Li, Y.-F.; Xu, M.; Li, W.-Y.; Yang, M.; Li, R.-L.

    2015-01-01

    RuPeng15 Powder (RPP15) is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses antigout, anti-inflammatory, and antihyperuricemic properties based on the traditional conceptions. The present study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty arthritis induced by monosodium urate (MSU) crystals. In the present study, we found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg) in rats with gouty arthritis induced by MSU crystals significantly attenuated the knee swelling. Histomorphometric and immunohistochemistry analyses revealed that MSU-induced inflammatory cell infiltration and the elevated expressions of nuclear transcription factor-κB p65 (NF-κB p65) in synovial tissues were significantly inhibited, and enzyme-linked immunosorbent assay (ELISA) result showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8) in synovial fluid were reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg). We conclude that RPP15 may be a promising candidate for the development of a new treatment for gout and its activity of antigout may be partially related to inhibiting TNF-α, IL-1β, IL-8, and NF-κB p65 expression in the synovial tissues. PMID:26221174

  18. Serum level of oxidative stress marker is dramatically low in patients with rheumatoid arthritis treated with tocilizumab.

    PubMed

    Hirao, Makoto; Yamasaki, Naomi; Oze, Hiroki; Ebina, Kosuke; Nampei, Akihide; Kawato, Yoshitaka; Shi, Kenrin; Yoshikawa, Hideki; Nishimoto, Norihiro; Hashimoto, Jun

    2012-12-01

    Regarding the pathobiology of rheumatoid arthritis, oxidative stress induced by reactive oxygen species is an important mechanism that underlies destructive and proliferative synovitis. Abundant amounts of reactive oxygen species have been detected in the synovial fluid of inflamed rheumatoid joints. It is reported that drugs that block tumor necrosis factor-α reduce the oxidative stress marker levels in patients with rheumatoid arthritis. In this study, we measured reactive oxygen species using a free radical analytical system in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, tumor necrosis factor-α-blocking drugs (infliximab, etanercept), and an interleukin-6-blocking drug (tocilizumab). The serum level of oxidative stress was drastically low in patients with rheumatoid arthritis treated with tocilizumab, suggesting that interleukin-6 blocking therapy reduces not only joint damage, but also vascular degeneration in patients with rheumatoid arthritis. We believe that such a drastic effect would reduce the incidence of cardiovascular events and mortality in patients with rheumatoid arthritis. PMID:21909945

  19. Therapeutic Effects of Chinese Medicine Herb Pair, Huzhang and Guizhi, on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats Revealed by Anti-Inflammatory Assessments and NMR-Based Metabonomics

    PubMed Central

    Han, Bin; Huang, Huizhu; Li, Zhong; Gong, Mengjuan; Shi, Wan; Zhu, Chunxia; Gu, Zulian; Zou, Zhongjie

    2016-01-01

    The present study was undertaken to evaluate the therapeutic effects of Huzhang-Guizhi herb pair (HG), firstly included in Hu-Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals-induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) production in synovial fluid as well as nuclear transcription factor-κB p65 (NF-κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU-induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU-induced gouty arthritis in rats. PMID:26989428

  20. Therapeutic Effects of Chinese Medicine Herb Pair, Huzhang and Guizhi, on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats Revealed by Anti-Inflammatory Assessments and NMR-Based Metabonomics.

    PubMed

    Han, Bin; Huang, Huizhu; Li, Zhong; Gong, Mengjuan; Shi, Wan; Zhu, Chunxia; Gu, Zulian; Zou, Zhongjie

    2016-01-01

    The present study was undertaken to evaluate the therapeutic effects of Huzhang-Guizhi herb pair (HG), firstly included in Hu-Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals-induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) production in synovial fluid as well as nuclear transcription factor-κB p65 (NF-κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU-induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU-induced gouty arthritis in rats. PMID:26989428

  1. Rheumatoid Arthritis

    MedlinePlus

    ... Rheumatoid Arthritis What Is Rheumatoid Arthritis? An Inflammatory, Autoimmune Disease Rheumatoid arthritis is an inflammatory disease that causes ... sometimes feverish. Rheumatoid arthritis is classified as an autoimmune disease. An autoimmune disease occurs when the immune system ...

  2. Synovial chondromatosis in raptors.

    PubMed

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

    1999-01-01

    Fourteen raptors, consisting of 13 great horned owls (Bubo virginianus) and one red-tailed hawk (Buteo jamaicensis), from central and north central Minnesota, western Wisconsin, and eastern South Dakota (USA) were admitted to a raptor rehabilitation center between June 1992 and June 1995, with perisynovial and synovial chondromatosis affecting multiple joints. Birds were severely debilitated primarily due to loss of shoulder motion. The etiology of these lesions in raptors is unknown. PMID:10073365

  3. Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis

    PubMed Central

    Andrés Cerezo, Lucie; Kuklová, Markéta; Hulejová, Hana; Vernerová, Zdeňka; Kaspříková, Nikola; Veigl, David; Pavelka, Karel; Vencovský, Jiří; Šenolt, Ladislav

    2015-01-01

    Objective. Progranulin (PGRN) is implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to assess the relationship between PGRN and disease activity in RA. Methods. PGRN levels were evaluated in patients with RA (n = 47) and OA (n = 42) and healthy controls (n = 41). Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP), disease activity score (DAS28-CRP), and health assessment questionnaire (HAQ) was studied. Results. Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1 ± 100.2 and 221.5 ± 102.5 versus 128.1 ± 34.7 ng/mL; P < 0.001). Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5 ± 275.3 versus 241.4 ± 165.2 ng/mL; P = 0.002). PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r = 0.327, P = 0.049) and HAQ score (r = 0.323, P = 0.032), while synovial fluid PGRN correlated only with HAQ (r = 0.310, P = 0.043) in patients with RA. PGRN levels were not associated with CRP or autoantibodies. Conclusions. This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA. PMID:26339140

  4. Glycosaminoglycan concentration in synovium and other tissues of rabbit knee in relation to synovial hydraulic resistance.

    PubMed

    Price, F M; Levick, J R; Mason, R M

    1996-09-15

    1. The hydraulic resistance of the synovial lining of a joint, a key coupling coefficient in synovial fluid turnover, is thought to depend on the concentration of biopolymers (glycosaminoglycans (GAGs) and collagen) in the synovial intercellular spaces, because these polymers create hydraulic drag. The primary aim of this study was to obtain microscopically separated, milligram samples of the very thin synovium from eight rabbit knees, and to analyse these quantitatively for GAGs (chondroitin sulphate, heparan sulphate and hyaluronan) and collagen to allow comparison with published hydraulic resistance data. Synovial fluid and femoral cartilage were also studied. 2. Synovium comprised 73 +/- 3% water by weight (mean +/- S.E.M.). Of the 270 mg solid per gram of wet tissue, protein formed 136 mg (by automated amino acid analysis), and of this 94 mg was collagen by hydroxyproline analysis. From the collagen mass and fibril volume fraction (0.153 of tissue by morphometry), fibrillar specific volume was calculated to be 1.43 ml per gram of molecular collagen, and fibril water content 47% by volume. 3. The concentration of chondroitin 4-sulphate (C4S) plus chondroitin 6-sulphate (C6S), measured by capillary zone electrophoresis was 0.55 mg per gram of synovium--much greater than in synovial fluid (0.04 mg g-1) and much less than in cartilage (27.8 mg g-1). The C4S/C6S ratio in synovium (7.3) differed from that in cartilage (0.7), indicating that different proteoglycans predominated in synovium. The heparan sulphate concentration, assayed by radioactive Ruthenium Red binding, was 0.92 mg per gram of synovium (synovial fluid, 0.08 mg g-1; cartilage, 0.72 mg g-1). 4. In contrast to sulphated GAGs, the hyaluronan concentration was highest in synovial fluid (3.53 mg g-1; biotinylated G1 domain binding assay). The concentration in synovial interstitium was only 0.56 mg g-1 (corrected for interstitial volume fraction, 0.66), even though there is open contact between synovial

  5. Antinociceptive and anti-inflammatory effects of Caryocar coriaceum Wittm fruit pulp fixed ethyl acetate extract on zymosan-induced arthritis in rats.

    PubMed

    de Oliveira, Francisco Fábio Bezerra; de Araújo, Joana Cláudia Bezerra; Pereira, Anamaria Falcão; Brito, Gerly Anne Castro; Gondim, Delane Viana; Ribeiro, Ronaldo de Albuquerque; de Menezes, Irwin Rose Alencar; Vale, Mariana Lima

    2015-11-01

    The ethyl acetate extract from the fruit pulp of Caryocar coriaceum Wittm (Caryocaraceae), popularly known as pequi, has wide applications in popular medicine. Preclinical tests have demonstrated the therapeutic properties of the oil. We investigated the antinociceptive and anti-inflammatory effects of Pequi C. coriaceum Wittm ethyl acetate extract (PCCO) on zymosan-induced arthritis in rat knee joint. The animals were pretreated with PCCO for 7 consecutive days or with a single dose. Paw elevation time (PET), leukocyte infiltration, myeloperoxidase activity (MPO) and cytokine levels were assessed 4h after zymosan injection. Synovial tissue was harvested for immunohistochemical analysis, edema and vascular permeability. We observed a significant decrease in PET with PCCO pretreatment. PCCO showed a significant reduction of leukocyte migration and a decrease in MPO. Decreases were observed in cytokine release in the synovial fluid and TNF-α and cyclooxygenase-1 immunostaining in synovial tissue. Edema was inhibited by treatment with all doses of PCCO. The data suggest that PCCO exerts antinociceptive and anti-inflammatory effects on arthritis in rats. PMID:26341615

  6. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis

    PubMed Central

    Khandpur, Ritika; Carmona-Rivera, Carmelo; Vivekanandan-Giri, Anuradha; Gizinski, Alison; Yalavarthi, Srilakshmi; Knight, Jason S.; Friday, Sean; Li, Sam; Patel, Rajiv M.; Subramanian, Venkataraman; Thompson, Paul; Chen, Pojen; Fox, David A.; Pennathur, Subramaniam; Kaplan, Mariana J.

    2013-01-01

    The early events leading to the development of rheumatoid arthritis (RA) remain unclear but formation of autoantibodies to citrullinated antigens (ACPA) is considered a key pathogenic phenomenon. Neutrophils isolated from patients with various autoimmune diseases display enhanced extracellular trap formation (NETs), a phenomenon that externalizes autoantigens and immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and synovial fluid RA neutrophils, compared to neutrophils from healthy controls and from patients with osteoarthritis. Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. During NETosis, neutrophils externalized citrullinated autoantigens implicated in RA pathogenesis, whereas anti-citrullinated vimentin antibodies potently induced NET formation. The inflammatory cytokines IL-17A and TNF-α induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease. PMID:23536012

  7. Glenohumeral Synovial Chondromatosis.

    PubMed

    Andrade, Robert

    2016-09-01

    A 20-year-old, right hand-dominant man reported to physical therapy with a history of deep anterior left shoulder pain. Radiographs, which were obtained after physical therapy was initiated, and subsequent magnetic resonance imaging showed the presence of numerous radio-opaque loose bodies that followed bone signal characteristics dispersed throughout the glenohumeral joint, leading to a diagnosis of synovial chondromatosis. J Orthop Sports Phys Ther 2016;46(9):809. doi:10.2519/jospt.2016.0414. PMID:27581180

  8. [Synovial sarcoma. Case report].

    PubMed

    Deme, Dániel; Abdulfatah, Bishr; Telekes, András

    2016-02-01

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

  9. Incidence and specificity of antibodies to types I, II, III, IV, and V collagen in rheumatoid arthritis and other rheumatic diseases as measured by 125I-radioimmunoassay

    SciTech Connect

    Stuart, J.M.; Huffstutter, E.H.; Townes, A.S.; Kang, A.H.

    1983-07-01

    Antibodies to human native and denatured types I, II, III, IV, and V collagens were measured using 125I-radioimmunoassay. Mean levels of binding by sera from 30 rheumatoid arthritis patients were significantly higher than those from 20 normal subjects against all of the collagens tested. The relative antibody concentration was higher in synovial fluid than in simultaneously obtained serum. Many patients with gout or various other rheumatic diseases also had detectable anticollagen antibodies. With a few notable exceptions, the majority of the reactivity detected in all patient groups was directed against covalent structural determinants present on all of the denatured collagens, suggesting a secondary reaction to tissue injury.

  10. LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro-inflammatory cytokines and MMP-9 in macrophages

    PubMed Central

    Kim, Won-Jung; Kang, Yoon-Joong; Koh, Eun-Mi; Ahn, Kwang-Sung; Cha, Hoon-Suk; Lee, Won-Ha

    2005-01-01

    Macrophages play a crucial role in the perpetuation of inflammation and irreversible cartilage damage during the development of rheumatoid arthritis (RA). LIGHT (TNFSF14) and its receptor TR2 (TNFRSF14) are known to have pro-inflammatory activities in foam cells of atherosclerotic plaques. We tested a hypothesis that LIGHT and TR2 are involved in activation of monocyte/macrophages in RA synovium. Immunohistochemical analysis of RA synovial tissue samples revealed that both LIGHT and TR2 are expressed in CD68 positive macrophages. In contrast, synovial tissue samples from osteoarthritis (OA) patients failed to reveal the expression of LIGHT. Expression of TR2 in RA synovial macrophages was also detected using flow cytometry analysis. To identify the role of LIGHT in the functioning of macrophages in RA, we isolated macrophage enriched cells from RA synovial fluid and stimulated them with LIGHT. LIGHT induced expression of matrix metalloproteinase-9 and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. These data indicate that LIGHT and TR2 expressed in macrophages are involved in the pathogenesis of RA by inducing the expression pro-inflammatory cytokines and matrix degrading enzymes. PMID:15667572

  11. Functional analysis of an arthritogenic synovial fibroblast

    PubMed Central

    Aidinis, Vassilis; Plows, David; Haralambous, Sylva; Armaka, Maria; Papadopoulos, Petros; Kanaki, Maria Zambia; Koczan, Dirk; Thiesen, Hans Juergen; Kollias, George

    2003-01-01

    Increasing attention has been directed towards identifying non-T-cell mechanisms as potential therapeutic targets in rheumatoid arthritis. Synovial fibroblast (SF) activation, a hallmark of rheumatoid arthritis, results in inappropriate production of chemokines and matrix components, which in turn lead to bone and cartilage destruction. We have demonstrated that SFs have an autonomous pathogenic role in the development of the disease, by showing that they have the capacity to migrate throughout the body and cause pathology specifically to the joints. In order to decipher the pathogenic mechanisms that govern SF activation and pathogenic potential, we used the two most prominent methods of differential gene expression analysis, differential display and DNA microarrays, in a search for deregulated cellular pathways in the arthritogenic SF. Functional clustering of differentially expressed genes, validated by dedicated in vitro functional assays, implicated a number of cellular pathways in SF activation. Among them, diminished adhesion to the extracellullar matrix was shown to correlate with increased proliferation and migration to this matrix. Our findings support an aggressive role for the SF in the development of the disease and reinforce the perspective of a transformed-like character of the SF. PMID:12723986

  12. Nitric Oxide-Driven Hypoxia Initiates Synovial Angiogenesis, Hyperplasia and Inflammatory Lesions in Mice

    PubMed Central

    Bao, Fei; Wu, Pei; Xiao, Na; Qiu, Frank; Zeng, Qing-Ping

    2012-01-01

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

  13. Rheumatoid Arthritis

    MedlinePlus

    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. Viral arthritis

    MedlinePlus

    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.

  15. RhoA/ROCK-dependent pathway is required for TLR2-mediated IL-23 production in human synovial macrophages: suppression by cilostazol.

    PubMed

    Park, So Youn; Lee, Sung Won; Lee, Won Suk; Rhim, Byung Yong; Lee, Seung Jin; Kwon, Sang Mo; Hong, Ki Whan; Kim, Chi Dae

    2013-11-01

    IL-23 is produced by antigen presenting cells and plays critical roles in immune response in rheumatoid arthritis. In this study, we investigated whether the RhoA/Rho-kinase pathway is required to elevate TLR2-mediated IL-23 production in synovial macrophages from patients with rheumatoid arthritis (RA), and then examined the suppressive effect of cilostazol on these pathways. IL-23 production was elevated by lipoteichoic acid (LTA), a TLR2 ligand, and this elevation was more prominent in RA macrophages than in those from peripheral blood of normal control. LTA increased the activation of RhoA in association with increased the nuclear translocation of NF-κB and its DNA-binding activity. Pretreatment of RA macrophages with the pharmacological inhibitors exoenzyme C3 (RhoA), Y27632 (Rho-kinase) or BAY11-7082 (NF-κB) inhibited IL-23 production by LTA. Inhibition of the RhoA/Rho-kinase pathway by these drugs attenuated NF-κB activation. Cilostazol suppressed the TLR2-mediated activation of RhoA, decreased NF-κB activity with down-regulated IL-23 production, and these effects were reversed by Rp-cAMPS, as an inhibitor of cAMP-dependent protein kinase. The expression of IL-23, which colocalized with CD68⁺ cells in knee joint of CIA mice, was significantly attenuated by cilostazol along with the decreased severity of arthritis. Taken together, the RhoA/Rho-kinase pathway signals TLR2-stimulated IL-23 production in synovial fluid macrophages via activation of NF-κB. Thus it is summarized that cilostazol suppresses TLR2-mediated IL-23 production by suppressing RhoA pathway via cAMP-dependent protein kinase activation. PMID:23973526

  16. Fucosyltransferase 1 mediates angiogenesis in rheumatoid arthritis

    PubMed Central

    Isozaki, Takeo; Amin, Mohammad A.; Ruth, Jeffrey H.; Campbell, Phillip L.; Tsou, Pei-Suen; Ha, Christine M.; Stinson, W. Alex; Domino, Steven E.; Koch, Alisa E.

    2015-01-01

    Objective The aim of this study was to determine the role of α(1,2)-linked fucosylation of proteins by fucosyltransferase1 (fut1) in rheumatoid arthritis (RA) angiogenesis. Methods Analysis of α(1,2)-linked fucosylated proteins in synovial tissues (STs) was performed by immunohistological staining. α(1,2)-linked fucosylated angiogenic chemokine expression in synovial fluids (SFs) was determined by immunoprecipitation and lectin blotting. To determine the angiogenic role of α(1,2)-linked fucosylated proteins in RA, we performed human dermal microvascular endothelial cell (HMVEC) chemotaxis and Matrigel assays using nondepleted and α(1,2)-linked fucosylated protein depleted RA SFs. To examine the production of proangiogenic chemokines by fucosyltransferase 1 (fut1) in HMVECs, cells were transfected with fut1 sense or antisense oligonucleotides, and enzyme-linked immunosorbent assay was performed. We then studied mouse lung endothelial cell (MLEC) chemotaxis using wild type and fut1 gene deficient MLECs. Results α(1,2)-linked fucosylated proteins on RA ST endothelial cells (ECs) were highly expressed compared to normal ST. α(1,2)-linked fucosylated monocyte chemoattract protein-1 (MCP-1)/CCL2 was present in RA SFs, and was significantly elevated compared to osteoarthritis SFs. Depletion of α(1,2)-linked fucosylated proteins in RA SFs induced less HMVEC migration and tube formation compared to nondepleted RA SFs. We found that blocking fut1 expression in ECs resulted in decreased MCP-1/CCL2 and regulated upon activation and normal T cell expressed and secreted (RANTES)/CCL5 production. Finally, we showed that fut1 regulates EC migration in response to vascular endothelial cell growth factor. Conclusions α(1,2)-linked fucosylation by fut1 may be an important new target for angiogenic diseases like RA. PMID:24692243

  17. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

    SciTech Connect

    Kitahara, Kanako; Kusunoki, Natsuko; Kakiuchi, Terutaka; Suguro, Toru; Kawai, Shinichi

    2009-01-09

    The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

  18. Synovial sarcoma in childhood

    SciTech Connect

    Israels, S.J.; Chan, H.S.L.; Daneman, A.; Weitzman, S.S.

    1984-04-01

    The clinical and radiologic findings in seven children with synovial sarcoma are described. The five boys and two girls had a mean age at presentation of 4.4 years. All seven had the lesion situated in an extremity. Plain radiographs in four revealed the presence of a soft-tissue mass with no calcification or bone and joint involvement. In two patients studied with computed tomography (CT), the primary lesions had peripheral irregular areas of enhancement with central areas of poor enhancement, reflecting the necrotic, cystic, and hemorrhagic changes found in the centers of these tumors. Although the exact margins of these lesions were difficult to define accurately even with intravenous contrast enhancement, CT is still recommended as the best imaging method for assessing the local extent of the primary tumor and is a useful tool in the planning of appropriate therapy as well as the gauging of the tumor response to ongoing treatment.

  19. Reactive arthritis in relation to internal derangements of the temporomandibular joint: a case control study.

    PubMed

    Lund, Bodil; Holmlund, Anders; Wretlind, Bengt; Jalal, Shah; Rosén, Annika

    2015-09-01

    The aim of this study was to find out if reactive arthritis was involved in the aetiology of chronic closed lock of the temporomandibular joint (TMJ) by looking for bacterial antigens in the synovial membrane of the TMJ, and by studying the antibody serology and carriage of human leucocyte antigen (HLA) B27 in patients with chronic closed lock. Patients with reciprocal clicking and healthy subjects acted as controls. We studied a total of 43 consecutive patients, 15 with chronic closed lock, 13 with reciprocal clicking, and 15 healthy controls with no internal derangements of the TMJ. Venous blood samples were collected from all subjects for measurement of concentrations of HLA tissue antigen and serology against Chlamydia trachomatis, Yersinia enterocolitica, Salmonella spp., Campylobacter jejuni, and Mycoplasma pneumoniae. Samples of synovial tissue from patients with closed lock and reciprocal clicking were obtained during discectomy and divided into two pieces, the first of which was tested by strand displacement amplification for the presence of C trachomatis, and the second of which was analysed for the presence of species-specific bacterial DNA using 16s rRNA pan-polymerase chain reaction (PCR). There were no significant differences between the groups in the incidence of antibodies against M pneumoniae, Salmonella spp. or Y enterocolitica. No patient had antibodies towards C trachomatis or C jejuni. We found no bacterial DNA in the synovial fluid from any patient. The HLA B27 antigen was present in 2/15 subjects in both the closed lock and control groups, and none in the reciprocal clicking group. In conclusion, reactive arthritis does not seem to be the mechanism of internal derangement of the TMJ. PMID:25957137

  20. Candida Arthritis: Analysis of 112 Pediatric and Adult Cases

    PubMed Central

    Gamaletsou, Maria N.; Rammaert, Blandine; Bueno, Marimelle A.; Sipsas, Nikolaos V.; Moriyama, Brad; Kontoyiannis, Dimitrios P.; Roilides, Emmanuel; Zeller, Valerie; Taj-Aldeen, Saad J.; Miller, Andy O.; Petraitiene, Ruta; Lortholary, Olivier; Walsh, Thomas J.

    2016-01-01

    Background. Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods. Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results. Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1–84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (≥3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10–141) and C reactive protein 26 mg/dL (0.5–95). Synovial fluid median white blood cell count was 27 500/µL (range, 100–220 000/µL) with 90% polymorphonuclear neutrophils (range, 24–98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion. Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse

  1. Candida Arthritis: Analysis of 112 Pediatric and Adult Cases.

    PubMed

    Gamaletsou, Maria N; Rammaert, Blandine; Bueno, Marimelle A; Sipsas, Nikolaos V; Moriyama, Brad; Kontoyiannis, Dimitrios P; Roilides, Emmanuel; Zeller, Valerie; Taj-Aldeen, Saad J; Miller, Andy O; Petraitiene, Ruta; Lortholary, Olivier; Walsh, Thomas J

    2016-01-01

    Background.  Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods.  Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results.  Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1-84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (≥3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10-141) and C reactive protein 26 mg/dL (0.5-95). Synovial fluid median white blood cell count was 27 500/µL (range, 100-220 000/µL) with 90% polymorphonuclear neutrophils (range, 24-98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion.  Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite

  2. Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response

    PubMed Central

    Kragstrup, Tue Wenzel; Jalilian, Babak; Keller, Kresten Krarup; Zhang, Xianwei; Laustsen, Julie Kristine; Stengaard-Pedersen, Kristian; Hetland, Merete Lund; Hørslev-Petersen, Kim; Junker, Peter; Østergaard, Mikkel; Hauge, Ellen-Margrethe; Hvid, Malene; Vorup-Jensen, Thomas; Deleuran, Bent

    2016-01-01

    Introduction In rheumatoid arthritis (RA) immune activation and presence of autoantibodies may precede clinical onset of disease, and joint destruction can progress despite remission. However, the underlying temporal changes of such immune system abnormalities in the inflammatory response during treat-to-target strategies remain poorly understood. We have previously reported low levels of the soluble form of CD18 (sCD18) in plasma from patients with chronic RA and spondyloarthritis. Here, we study the changes of sCD18 before and during treatment of early RA and following arthritis induction in murine models of rheumatoid arthritis. Methods The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1) plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort), 2) plasma from chronic RA patients, 3) serum from SKG and CIA mice following arthritis induction, and 4) supernatants from synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from 6 RA patients cultured with TNFα or adalimumab. Results Plasma levels of sCD18 were decreased in chronic RA patients compared with early RA patients and in early RA patients compared with healthy controls. After 12 months of treatment the levels in early RA patients were similar to healthy controls. This normalization of plasma sCD18 levels was more pronounced in patients with very early disease who achieved an early ACR response. Plasma sCD18 levels were associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above baseline followed by a decline. Shedding of CD18 from RA SFMC and RA PBMC cultures was increased by TNFα and decreased by adalimumab. Conclusions The plasma sCD18 levels were altered

  3. Juvenile Arthritis

    MedlinePlus

    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 ...

  4. Psoriatic arthritis

    SciTech Connect

    Gerber, L.H.; Espinoza, L.R.

    1985-01-01

    This book contains 11 chapters. Some of the titles are: The history and epidemiologic definition of psoriatic arthritis as a distinct entity; Psoriatic arthritis: Further epidemiologic and genetic considerations; The radiologic features of psoriatic arthritis; and Laboratory findings and pathology of psoriatic arthritis.

  5. Hemorrhagic Synovial Cyst Associated with Rheumatoid Atlantoaxial Subluxation

    PubMed Central

    Sheen, Jae Jon; Seo, Dong Kwang; Choi, Seung Ho

    2013-01-01

    Synovial cyst on prevertebral space of C1-2 joint is rare but may be associated hemorrhagic event. We describe a case of a 72-year-old woman who presented with sudden severe headache in her left occipital area with dyspnea. She had rheumatoid arthritis for 14-years. Large hemorrhagic cystic mass was seen around prevertebral space of the atlantoaxial joint on the left side on cervical MRI (magnetic resonance image) and it obstructed the nasopharyngeal cavity. Aspiration of the cystic lesion was performed via transoral approach, followed by posterior occipito-cervical fusion. The specimen was xanthochromic, suggesting old hemorrhage. The patient was tolerable on her postoperative course and showed good respiration and relieved headache. We suggest that repeated microtrauma due to atalantoaxial subluxation associated with rheumatoid arthritis as a main cause of hemorrhagic event on the cyst. PMID:24757465

  6. NLRP3 Inflammasome Plays an Important Role in the Pathogenesis of Collagen-Induced Arthritis

    PubMed Central

    Zhang, Yongfeng; Zheng, Yi; Li, Hongbin

    2016-01-01

    Objective. To investigate the relationship between NLRP3 and the pathogenesis of collagen-induced arthritis. Methods. We used the collagen-induced arthritis (CIA) mouse model. The mice were divided into two groups: the model group (CIA, n = 16) and the control group (Normal, n = 8). The mice were sacrificed seven weeks after immunization. The arthritis score and imaging evaluation (X-rays, Micro-CT, and MRI) were performed. Synovial tissue NLRP3 expression and peripheral blood cytokine levels were analyzed. Results. The arthritis score (6.00 ± 2.52), imaging score (4.63 ± 0.92), and synovial tissue NLRP3 expression (4.00 ± 2.03) significantly increased in the CIA mice. The expression of synovial NLRP3 was positively correlated with arthritis clinical and radiographic scores (r = 0.792 and r = 0.669, resp.). Conclusions. The synovial NLRP3 expression increased at the early onset of RA. Synovial NLRP3 expression level was correlated with the clinical arthritis severity and extent of radiological destruction, suggesting that NLRP3 is involved in the pathogenesis of RA. PMID:27034595

  7. Interleukin-18 expression in rheumatoid artheritis synovial tissue and its relation to disease activity.

    PubMed

    Gouda, Elsayed A; Aboulata, Alaa A; Elharoun, Ahmed S; Tawfik, Abdel Hamid; Hossney, Ahmed; Reda, Ali M; Desoky, Khaled M

    2007-01-01

    The study investigates the expression and function of interleukin-18 (IL-18) in synovial tissue (ST) of patients with rheumatoid arthritis (RA). IL-18 and IL-18 receptors (IL-18R) mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). Expression of IL-18 at protein level was analyzed by western blotting technique. Cytokines; (IL-18 and interferon-[IFN-gamma]) in culture supernatants from ST cell organ and synovial cultures and IL-18 in sera and synovial fluid (SF) were measured by ELISA. The ST samples were taken from 44 RA patients and thirty osteoarthritis patients (OA) were included as controls. Using RT-PCR, for ST of RA and OA, mRNA expression of IL-18 was detected in 39 out of 44 (88.6%) RA patients and in 14 out of 30 (46.6%) OA controls. However, mRNA expression of IL-18 R alpha and beta chains were detected in 39 and 35 out of 44 (88.6% and 79.5%) RA patients, respectively. ST of OA did not express mRNA of alpha and beta chains of IL-18 R. In vitro study of IL-18 production by ST showed significantly higher levels in RA compared to that of OA patients (P<0.005). Western blotting revealed that the expression of ST IL-18 was more in RA than in OA (P < 0.02). Only IL-12, but not IL-18, stimulates IFN-gamma production by RAST cells [mean +/- SD = 246 +/- 15 pg/ml]. However, when IL-12 was combined with IL-18, they could significantly stimulate IFN-gamma production by RAST cells [M +/- SD = 629 +/- 18 pg/ml]. OA ST cells did not respond to either IL-12 alone or when combined to IL-18. II-18 was detected at significantly higher levels in sera and SF of RA patients in comparison to OA controls (p < 0.001 and p < 0.01, respectively). IL-18 level in the sera and SF in RA patients was significantly correlated with disease activity. In conclusion, IL-18 is expressed in RA synovia and contributes to the production of IFN-gamma by the infiltrating T-cells. These cytokines could play a proinflammatory role in the pathogenesis of RA

  8. Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas derived from rheumatoid synovial tissue.

    PubMed

    Brown, C M; Longhurst, C; Haynes, G; Plater-Zyberk, C; Malcolm, A; Maini, R N

    1992-08-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects synovial joints. Activated B lymphocytes and plasma cells are present in the synovial tissue and are thought to contribute to the immunopathology of the rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have generated B cell hybridomas from synovial tissue of an RA patient. Here we describe the immunoglobulin VH gene repertoire of eight IgM- and 10 IgG-secreting synovial-derived hybridomas. The VH4 gene family is highly represented (38.5%) in this panel of hybridomas compared with the frequency of VH4 gene expression in circulating B lymphocytes reported previously (19-22%) and with the VH4 gene frequency we observed in a panel of hybridomas derived in the same manner from the spleen and tonsil of normal individuals (19%). The increased frequency of VH4 gene expression was not due to the expansion of a single B cell clone in vivo as none of these hybridomas was clonally related. Two synovial-derived hybridomas secreted autoantibodies; one (VH3+) secreted an IgM-rheumatoid factor (RF) and the other (VH4+) secreted IgM with polyreactive binding to cytoskeletal proteins and cardiolipin. The antibodies secreted by the remaining synovial-derived hybridomas were not reactive with the autoantigens tested. The VH gene usage in a proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen provided preliminary evidence that CD5+ B cells in RA synovium have a similar increase of VH4 gene expression reported for CD5+ B cells from normal individuals and patients with chronic lymphocytic leukaemia. PMID:1379132

  9. Suppression of PU.1-linked TLR4 expression by cilostazol with decrease of cytokine production in macrophages from patients with rheumatoid arthritis

    PubMed Central

    Park, SY; Lee, SW; Baek, SH; Lee, CW; Lee, WS; Rhim, BY; Hong, KW; Kim, CD

    2013-01-01

    Background and Purpose The present study assessed the effects of cilostazol on LPS-stimulated TLR4 signal pathways in synovial macrophages from patients with rheumatoid arthritis (RA). These effects were confirmed in collagen-induced arthritis (CIA) in mice. Experimental Approach Expression of TLR4, PU.1, NF-κB p65 and IκBα on synovial fluid macrophages from RA patients was determined by Western blotting, and cytokines were measured by elisa. Anti-arthritic effects were evaluated in CIA mice. Key Results Intracellular cAMP was concentration-dependently raised by cilostazol (1–100 μM). Cilostazol significantly suppressed LPS-stimulated increase of TLR4 expression by blocking PU.1 transcriptional activity in RA macrophages. In addition, cilostazol decreased LPS-induced myeloid differentiation factor 88 (MyD88) expression, but not that of TNF receptor-associated factor 6 (TRAF6). Cilostazol also suppressed IkBα degradation and NF-κB p65 nuclear translocation. Moreover, LPS-induced increase of cytokine production (TNF-α, IL-1β) was inhibited by cilostazol, an effect which was accompanied by suppression of IκBα degradation, and NF-κB p65 nuclear translocation. However, expression of anti-inflammatory IL-10 was elevated by cilostazol and forskolin/IBMX. In mice with CIA, post-treatment with cilostazol (30 mg kg−1 day−1) decreased expression of TLR4 in knee joints in association with decreased recruitment of macrophages. Consequently, synovial inflammation, proteoglycan depletion and bone erosion were significantly inhibited by cilostazol treatment. Conclusions and Implications Cilostazol down-regulated LPS-stimulated PU.1-linked TLR4 expression and TLR4/MyD88/NF-κB signal pathways, and then suppressed inflammatory cytokine production in synovial macrophages from RA patients. Also cilostazol markedly inhibited the severity of CIA in mice. PMID:23072581

  10. Inhibition of Inflammatory Arthritis Using Fullerene Nanomaterials

    PubMed Central

    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. PMID:25879437

  11. Lipid bilayer membranes: Missing link in the comprehension of synovial lubrication?

    NASA Astrophysics Data System (ADS)

    Packard, Ross; Cowley, Leonie; Dubief, Yves

    2010-03-01

    The human body hosts an extremely efficient tribological system in its synovial joints that operate under very low friction and virtually no wear. It has long been assumed that the higher molecular weight molecules present in the synovial fluid (hyaluronic acid, lubricin) are solely responsible for the mechanical properties of joint. Smaller components, unsaturated phospholipids, have a virtually an undefined role, most probably because of the cancellation of their amphiphilic properties ex vivo caused by oxidation. Using experimental observations of multilamellar arrangements in synovial joints, we formulate the assumption that self-assembling structures provide the anisotropy necessary to synovial fluid to resist drainage under normal compression. Our molecular dynamics simulations demonstrate the tremendous mechanical properties of lipid bilayers and also highlight their weakening consistent with modifications resulting from injuries or joint prosthesis.

  12. Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats.

    PubMed

    Pal, Rishi; Chaudhary, Manju J; Tiwari, Prafulla C; Babu, Suresh; Pant, K K

    2015-12-01

    Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (p<0.05 in all parameters) compared to only adjuvant control group. It also reversed adjuvant induced slight decrease in body weight to normalcy. l-Arginine 100mg/kg+theophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (p<0.001). Synovial TNF-α level of adjuvant only group was several fold higher than its serum level. Treatment with theophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05). PMID:26349791

  13. Complement in acute and chronic arthritides: assessment of C3c, C9, and protectin (CD59) in synovial membrane.

    PubMed Central

    Konttinen, Y T; Ceponis, A; Meri, S; Vuorikoski, A; Kortekangas, P; Sorsa, T; Sukura, A; Santavirta, S

    1996-01-01

    OBJECTIVES: To investigate the role of complement cascade induced damage and protection against it in acute arthritides compared to rheumatoid arthritis and other chronic joint derangements. METHODS: C3c, C9, and protectin (CD59) were examined by avidin-biotin-peroxidase complex staining. RESULTS: Marked deposits of C3c and C9 were found in synovial vasculature and intercellular matrix of the lining in rheumatoid arthritis and in acute arthritides (including bacterial, reactive, and osteoarthritis flare up). Furthermore, protectin was not visible in synovial lining cells and was relatively weakly expressed in stromal and endothelial cells in rheumatoid arthritis; also in acute arthritides protectin expression was weak. In contrast, C3c and C9 deposits were not found in chronic conditions associated with degenerative diseases (osteoarthritis and osteochondritis dissecans) or mechanical causes (patellar luxation and a ruptured meniscus), in which also the protectin expression was prominent in synovial lining, endothelial and some stromal cells. CONCLUSIONS: Activation of the complement in rheumatoid arthritis and in acute arthritides seems to be associated with a decreased protection of synovial cells against cellular effects and lysis mediated by membrane attack complex. Images PMID:9014582

  14. Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment

    SciTech Connect

    Hanly, J.G.; Hassan, J.; Moriarty, M.; Barry, C.; Molony, J.; Casey, E.; Whelan, A.; Feighery, C.; Bresnihan, B.

    1986-01-01

    Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis.

  15. Erosive osteoarthritis, psoriatic arthritis and pseudogout; a casual association?

    PubMed

    Hoxha, Ariela; Ruffatti, Amelia; Alberioli, Enrico; Lorenzin, Mariagrazia; Oliviero, Francesca; Mattia, Elena; Punzi, Leonardo; Ramonda, Roberta

    2016-07-01

    According to recent hypothesis, the inflammation has a pivotal role in the onset and progression of erosive hand osteoarthritis (EHOA), psoriatic arthritis (PsA) and chondrocalcinosis (CC)/pseudogout. Albeit, it has been recognised for years as an association between EHOA and radiographic evidence of CC, but there are few reports of coexistence of microcrystalline arthritis and PsA. This is the first report that described a clinical experience concerning two consecutive cases of patients presented with EHOA, PsA and pseudogout. Two Caucasian women of 71 and 85 years old with a history of OA and mild psoriasis are presented with tenderness and swelling of first interphalangeal (IP) and wrist joint, respectively. Arthrocentesis performed at the first IP and wrist joint, respectively, showed an inflammatory synovial fluid with presence of calcium pyrophosphate dehydrate crystals. X-rays of hands, feet and knees showed characteristic features of EHOA, PsA and CC. Furthermore, HLA typing evinces the presence of HLA C*06; DRB*01 07 and HLA C*07; DRB*01 *11 alleles, respectively, predisposing factors of these inflammatory diseases. The relationship between these aggressive rheumatic diseases along with their clinical, radiographic, laboratory and genetic features is discussed. PMID:25833145

  16. Pericardial Synovial Sarcoma: A Rare Clinical Entity.

    PubMed

    Goldblatt, Joshua; Saxena, Pankaj; McGiffin, David C; Zimmet, Adam

    2015-11-01

    Synovial sarcoma is an extremely rare form of primary malignancy of the pericardium. We present a case of primary synovial sarcoma of the pericardium followed by a review of the literature. PMID:26347295

  17. Sonographic Findings in Gouty Arthritis: Diagnostic Value and Association with Disease Duration.

    PubMed

    Elsaman, Ahmed M; Muhammad, Eman M S; Pessler, Frank

    2016-06-01

    The objective of this work was to evaluate the sonographic features of gouty arthritis and correlate findings with disease duration. The study was conducted on 100 patients in ambulatory care aged ≥40 y. Inclusion criteria included mono- or oligo-arthritis with effusion of the knee or the first metatarsophalangeal (MTP) joint and no known history of gout. A complete medical history was obtained with emphasis on the known risk factors or causes of gouty arthritis. A 12-MHz Medison linear probe was used for ultrasonography (US). Synovial fluid analysis with polarizing light microscopy was performed on all patients. Ninety-eight knee joints and 33 first MTP joints were examined. Gouty arthritis was found by US in four forms: (i) floating echogenic foci in effusion fluid or Baker cysts, (ii) deposits on the cartilage surface (double contour sign), (iii) erosions and (iv) mature tophus/tophi. These were found in 78.9%, 42.3%, 39.4% and 28.2% of patients, respectively. The overall sensitivity and specificity of US in detecting gout (as defined by the clinical gold standard, i.e., detection of urate crystals by polarizing light microscopy) were 85.9% and 86.7%, respectively. Detection of echogenic foci in effusion fluid was associated with the shortest duration of symptoms (median duration 2 y) followed by double contour sign (3.5 y), erosions (4 y) and tophus (12.5 y). Sonographic findings in gout can be assigned a temporal pattern, with echogenic foci being associated with the shortest and full tophus formation with the longest disease duration. PMID:26995154

  18. Contribution of synovial lining cells to synovial vascularization of the rat temporomandibular joint.

    PubMed

    Nozawa-Inoue, Kayoko; Harada, Fumiko; Magara, Jin; Ohazama, Atsushi; Maeda, Takeyasu

    2016-03-01

    The lining layer of the synovial membrane in the temporomandibular joint (TMJ) contains two types of lining cells: macrophage-like type A and fibroblast-like type B cells. The type B cells are particularly heterogeneous in their morphology and immunoreactivity, so that details of their functions remain unclear. Some of the type B cells exhibit certain resemblances in their ultrastructure to those of an activated capillary pericyte at the initial stage of the angiogenesis. The articular surface, composed of cartilage and the disc in the TMJ, has few vasculatures, whereas the synovial lining layer is richly equipped with blood capillaries to produce the constituent of synovial fluid. The present study investigated at both the light and electron microscopic levels the immunocytochemical characteristics of the synovial lining cells in the adult rat TMJ, focusing on their contribution to the synovial vascularization. It also employed an intravascular perfusion with Lycopersicon esculentum (tomato) lectin to identify functional vessels in vivo. Results showed that several type B cells expressed desmin, a muscle-specific intermediate filament which is known as the earliest protein to appear during myogenesis as well as being a marker for the immature capillary pericyte. These desmin-positive type B cells showed immunoreactions for vimentin and pericyte markers (neuron-glial 2; NG2 and PDGFRβ) but not for the other markers of myogenic cells (MyoD and myogenin) or a contractile apparatus (αSMA and caldesmon). Immunoreactivity for RECA-1, an endothelial marker, was observed in the macrophage-like type A cells. The arterioles and venules inside the synovial folds extended numerous capillaries with RECA-1-positive endothelial cells and desmin-positive pericytes to distribute densely in the lining layer. The distal portion of these capillaries showing RECA-1-immunoreactivity lacked lectin-staining, indicating a loss of blood-circulation due to sprouting or termination in the

  19. Secondary synovial chondromatosis of the shoulder.

    PubMed

    Ji, Jong-Hun; Shafi, Mohamed; Jeong, Dong-Seok

    2015-09-01

    Synovial chondromatosis is classified as either primary or secondary. Primary synovial chondromatosis results from a proliferation of chondrocytes in the synovial membrane leading to the formation of cartilaginous loose bodies. Secondary synovial chondromatosis is a rare condition characterized by the growth of separated particles from the articular cartilage or osteophytes in joint diseases. The present article aims to report the secondary chondromatosis of the shoulder and to discuss the clinical manifestations, pathogenesis, diagnosis, histological findings and management of this condition. PMID:24803015

  20. Synovial Sarcoma With Myoid Differentiation.

    PubMed

    Qassid, Omar; Ali, Ahmed; Thway, Khin

    2016-09-01

    Synovial sarcoma is a malignant mesenchymal tumor with variable epithelial differentiation, which is defined by the presence of a specific t(X;18)(p11.2;q11.2) chromosomal translocation that generates SS18-SSX fusion oncogenes. Synovial sarcoma typically arises within extremity deep soft tissue (particularly around large joints) of young adults, but has been shown to occur at almost any location. When it arises in more unusual sites, such as the abdomen, it can present a significant diagnostic challenge. We describe a case of intraabdominal monophasic synovial sarcoma that immunohistochemically showed strong expression of smooth muscle actin and calponin but only very scanty cytokeratin, and which showed morphologic and immunohistochemical overlap with other spindle cell neoplasms that can arise at this site, such as gastrointestinal stromal tumor and myofibrosarcoma. As correct diagnosis is of clinical and prognostic importance, surgical pathologists should be aware of the potential for synovial sarcoma to occur at a variety of anatomic sites and of its spectrum of immunoreactivity. Synovial sarcoma should be in the differential diagnosis of spindle cell neoplasms with myoid differentiation that do not fall into any definite tumor category, for which there should be a relatively low threshold for performing fluorescence in situ hybridization or reverse transcription-polymerase chain reaction to assess for the specific SS18 gene rearrangement or SS18-SSX fusion transcripts, which remain the diagnostic gold standard. PMID:27106779

  1. Effects of Low-Level Laser Therapy, 660 nm, in Experimental Septic Arthritis

    PubMed Central

    Araujo, Bruna Formentão; Silva, Lígia Inez; Meireles, Anamaria; Rosa, Camila Thieimi; Gioppo, Nereida Mello da Rosa; Jorge, Alex Sandro; Kunz, Regina Inês; Ribeiro, Lucinéia de Fátima Chasko; Brancalhão, Rose Meire Costa; Bertolini, Gladson Ricardo Flor

    2013-01-01

    The effectiveness of low-level laser therapy (LLLT) in the presence of an infectious process has not been well elucidated. The aim of the study was to evaluate the effects of LLLT in an experimental model of septic arthritis. Methods. Twenty-one Wistar rats were divided as follows: control group, no bacteria; placebo group, bacteria were inoculated; Treated group, bacteria were injected and treatment with LLLTwas performed. To assess nociception, a von Frey digital analgesimeter was applied. Synovial fluid was streaked to analyze bacterial growth. The standard strain of S. aureus was inoculated in the right knee. LLLT was performed with 660 nm, 2 J/cm2, over 10 days. After treatment, the knees were fixed and processed for morphological analysis by light microscopy. Results. It was found that nociception increases in the right knee. There was a lack of results for the seeding of the synovial fluid. The morphological analysis showed slight recovery areas in the articular cartilage and synovia; however, there was the maintenance of the inflammatory infiltrate. Conclusion. The parameters used were not effective in the nociception reduction, even with the slight tissue recovery due to the maintenance of inflammatory infiltrate, but produced no change in the natural history of resolution of the infectious process. PMID:23997964

  2. Two- and three-dimensional optical tomography of finger joints for diagnostics of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Klose, Alexander D.; Hielscher, Andreas H.; Hanson, Kenneth M.; Beuthan, Juergen

    1998-12-01

    Rheumatoid arthritis (RA) is one of the most common diseases of human joints. This progressive disease is characterized by an inflammation process that originates in the inner membrane (synovalis) of the capsule and spreads to other parts of the joint. In early stages the synovalis thickness and the permeability of this membrane changes. This leads to changes in the optical parameters of the synovalis and the synovial fluid (synovia), which occupies the space between the bones. The synovia changes from a clear yellowish fluid to a turbid grayish substance. In this work we present 2 and 3-dimensional reconstruction schemes for optical tomography of the finger joints. Our reconstruction algorithm is based on the diffusion approximation and employs adjoint differentiation techniques for the gradient calculation of the objective function with respect to the spatial distribution of optical properties. In this way, the spatial distribution of optical properties within the joints is reconstructed with high efficiency and precision. Volume information concerning the synovial space and the capsula are provided. Furthermore, it is shown that small changes of the scattering coefficients can be monitored. Therefore, optical tomography has the potential of becoming a useful tool for the early diagnosis and monitoring of disease progression in RA.

  3. Synovial plicae of the knee

    SciTech Connect

    Apple, J.S.; Martinez, S.; Daffner, R.H.; Gehweiler, J.A.; Hardaker, W.T.

    1982-01-01

    This report describes the anatomy, patho-physiology, clinical, and radiographic findings, and treatment of the synovial plicae of the knee joint. The suprapatellar plica is a synovial fold present in the suprapatellar pouch of the knee joint in approximately 20% of the population. This fold may become symptomatic after injury and cause symptoms similar to other common internal derangements of the knee. Double contrast arthrography of the knee can be used to identify the presence of plicae. Although arthrography can identify the presence of a plica, its clinical significance requires close correlation with symptoms and an accurate clinical examination.

  4. T Cell Migration in Rheumatoid Arthritis

    PubMed Central

    Mellado, Mario; Martínez-Muñoz, Laura; Cascio, Graciela; Lucas, Pilar; Pablos, José L.; Rodríguez-Frade, José Miguel

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies. PMID:26284069

  5. T Cell Migration in Rheumatoid Arthritis.

    PubMed

    Mellado, Mario; Martínez-Muñoz, Laura; Cascio, Graciela; Lucas, Pilar; Pablos, José L; Rodríguez-Frade, José Miguel

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies. PMID:26284069

  6. The distribution and functional properties of dendritic cells in patients with seronegative arthritis.

    PubMed Central

    Stagg, A J; Harding, B; Hughes, R A; Keat, A; Knight, S C

    1991-01-01

    Dendritic cells (DC), potent antigen-presenting cells, are known to be increased in numbers in inflammatory lesions in rheumatoid arthritis and juvenile chronic arthritis. In this study, patients with seronegative arthritis were studied; the distribution and functional properties of DC enriched low density cells (LDC) from peripheral blood (PB) and synovial fluid (SF) were compared. The composition of LDC from both sources was similar, comprising approximately 30% DC, 60% monocytes with few T lymphocytes. SF was significantly enriched for LDC compared with paired peripheral blood (P less than 0.0001) or peripheral blood from healthy controls (P less than 0.001). In contrast, patient PB contained fewer LDC (P less than 0.05) overall than healthy controls. LDC from both sources were potent simulators of allogeneic PB T cells in a mixed leucocyte reaction (MLR), but in four out of 10 patients SF LDC were significantly more stimulatory. In autologous MLRs (AMLRs) SF T cells were not stimulated by either LDC population. This anergy of T cells was confined to the joint as patient PB T cells showed an AMLR response to PB LDC which was similar to that seen in cells from healthy controls. PB T cells also responded to SF LDC; in a minority of patients SF LDC caused significantly greater stimulation in AMLR than PB LDC and the possibility is discussed that this may represent presentation of antigen acquired in vivo. PMID:1826647

  7. Infectious Arthritis

    MedlinePlus

    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 ...

  8. Psoriatic Arthritis

    MedlinePlus

    ... 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 ...

  9. Arthritis Foundation

    MedlinePlus

    ... hour massage will be donated to the Arthritis Foundation! Jingle Bell Run Join us for the nation's ... a cure! Answers When You Need Them Arthritis Foundation licensed social workers provide 24/7 assistance on ...

  10. Fungal arthritis

    MedlinePlus

    ... and irritation (inflammation) of a joint by a fungal infection. It is also called mycotic arthritis. Causes Fungal ... symptoms of fungal arthritis. Prevention Thorough treatment of fungal infections elsewhere in the body may help prevent fungal ...

  11. Extra and Intra-articular Synovial Chondromatosis.

    PubMed

    Chaudhary, R K; Banskota, B; Rijal, S; Banskota, A K

    2015-01-01

    Synovial chondromatosis is not so rare intra-articular condition secondary to synovial metaplasia, that affects the knee joint. Extra-articular synovial chondromatosis however is an extremely rare condition that usually involves the synovial sheath or bursa of the foot or hand. We present two cases of synovial chondromatosis, one intra and one extra-articular. The first case was a 25 year old lady who presented with pain, swelling and restricted range of motion of left knee and was found to have an intra-articular synovial chondromatosis which was treated successfully by joint debridement. The second case was that of a 22 year old man who presented with right knee pain and was diagnosed to have an extra-articular synovial chondromatosis of his right medial hamstring tendon sheath, excision of which resulted in complete relief of symptoms. PMID:27549506

  12. Divergent T-Cell Cytokine Patterns in Inflammatory Arthritis

    NASA Astrophysics Data System (ADS)

    Simon, A. K.; Seipelt, E.; Sieper, J.

    1994-08-01

    A major immunoregulatory mechanism in inflammatory infections and allergic diseases is the control of the balance of cytokines secreted by Th1/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseases; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune diseases. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Th1-like pattern whereas in reactive arthritis interferon γ expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confirmed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic diseases by means of inhibitory cytokines.

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

    PubMed Central

    Cascão, Rita; Vidal, Bruno; Lopes, Inês P.; Paisana, Eunice; Rino, José; Moita, Luis F.; Fonseca, João E.

    2015-01-01

    Background Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA). Methods Celastrol was administered to AIA rats both in the early (4 days after disease induction) and late (11 days after disease induction) phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively. Results Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects. Conclusions Our results validate celastrol as a promising compound for the treatment of arthritis. PMID:26658436

  14. Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3

    PubMed Central

    MATSUSHITA, N; KASHIWAGI, M; WAIT, R; NAGAYOSHI, R; NAKAMURA, M; MATSUDA, T; HOGGER, P; GUYRE, P M; NAGASE, H; MATSUYAMA, T

    2002-01-01

    The aim of the present study was to evaluate levels of soluble CD 163 in sera and fluids from rheumatoid arthritis (RA) patients and elucidate the mechanism that regulates the shedding of CD163. Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting. To determine the effects of tissue inhibitors of metalloproteinase (TIMPs) on the shedding of CD163 from monocytes/macrophages, levels of soluble CD163 in cultures of monocytes/macrophages and the expression of CD163 on monocytes/macrophages in the presence or absence of TIMPs were examined by a sandwich enzyme immunoassay and flow cytometry, respectively. The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP. TIMP-3, but not TIMP-1 or TIMP-2, inhibited the shedding of CD163 from monocytes/macrophages. It was shown that serum levels of soluble CD163 are a sensitive and reliable marker to monitor activated macrophages in synovitis from RA patients and the results imply that the responsible proteinase for the shedding of CD163 is not a member of the matrix metalloproteinases, but is likely to be a member of ADAMs. PMID:12296867

  15. Persistent spontaneous synovial drainage from digital flexor sheath in proliferative tenosynovitis: Two case reports and a review of the literature.

    PubMed

    Chin, Brian; Cheung, Kevin; Farhangkhoee, Hana; Thoma, Achilleas

    2015-01-01

    Proliferative flexor tenosynovitis of the hand is an inflammatory process involving the synovial sheaths surrounding the tendons. It is most commonly caused by infection, but may also be caused by overuse, diabetes and rheumatic conditions such as rheumatoid arthritis and crystal arthropathies. The present report describes two patients with severe proliferative tenosynovitis, who developed a fistula between the tendon sheath and skin after instrumentation, resulting in persistent synovial drainage. After failing conservative management, both patients were managed with extensive flexor tenosynovectomy to prevent inoculation of bacteria into the flexor sheath. The presentation, management and outcome of each case is described in addition to a discussion of the literature on tenosynovial fistulas. PMID:26090353

  16. Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis.

    PubMed

    Cutolo, Maurizio; Seriolo, Bruno; Villaggio, Barbara; Pizzorni, Carmen; Craviotto, Chiara; Sulli, Alberto

    2002-06-01

    Generally, androgens exert suppressive effects on both humoral and cellular immune responses and seem to represent natural anti-inflammatory hormones; in contrast, estrogens exert immunoenhancing activities, at least on humoral immune response. Low levels of gonadal androgens (testosterone/dihydrotestosterone) and adrenal androgens (dehydroepiandrosterone and its sulfate), as well as lower androgen/estrogen ratios, have been detected in body fluids (that is, blood, synovial fluid, smears, salivary) of both male and female rheumatoid arthritis patients, supporting the possibility of a pathogenic role for the decreased levels of the immune-suppressive androgens. Several physiological, pathological, and therapeutic conditions may change the sex hormone milieu and/or peripheral conversion, including the menstrual cycle, pregnancy, the postpartum period, menopause, chronic stress, and inflammatory cytokines, as well as use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. Therefore, sex hormone balance is still a crucial factor in the regulation of immune and inflammatory responses, and the therapeutical modulation of this balance should represent part of advanced biological treatments for rheumatoid arthritis and other autoimmune rheumatic diseases. PMID:12114267

  17. Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

    PubMed

    Lattuada, D; Gualtierotti, R; Crotta, K; Seneci, P; Ingegnoli, F; Corradini, C; Viganò, R; Marelli, O; Casnici, C

    2016-01-01

    Rheumatoid arthritis (RA) is characterized by synovial inflammation and hyperplasia. Fibroblast-like synoviocytes (FLSs) are apoptosis-resistant and contribute to the pathogenesis of RA by producing cytokines and proteolytic enzymes, which degrade the extracellular matrix. We evaluated the proapoptotic and anti-inflammatory activity of the small molecule Smac127 on RA-FLSs cultured in synovial fluid (SF), in order to reproduce the physiopathological environmental characteristic of RA joints. In this context, Smac127 induces apoptosis by inhibiting apoptosis proteins (IAPs). This inhibition activates caspase 3 and restores the apoptotic pathway. In addition, Smac127 induces a significant inhibition of the secretion of IL-15 and IL-6, stimulation of pannus formation, and damage of bone and cartilage in RA. Also the secretion of the anti-inflammatory cytokine IL-10 is dramatically increased in the presence of Smac127. The cartilage destruction in RA patients is partly mediated by metalloproteinases; here we show that the MMP-1 production by fibroblasts cultured in SF is significantly antagonized by Smac127. Conversely, this molecule has no significant effects on RANKL and OPG production. Our observations demonstrate that Smac127 has beneficial regulatory effects on inflammatory state of RA-FLSs and suggest a potential use of Smac127 for the control of inflammation and disease progression in RA. PMID:26989333

  18. Vitamin D binding protein isoforms as candidate predictors of disease extension in childhood arthritis

    PubMed Central

    Gibson, David S.; Newell, Keri; Evans, Alexandra N.; Finnegan, Sorcha; Manning, Gwen; Scaife, Caitriona; McAllister, Catherine; Pennington, Stephen R.; Duncan, Mark W.; Moore, Terry L.; Rooney, Madeleine E.

    2012-01-01

    Introduction. Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic autoimmune diseases with variable clinical outcomes. We investigated whether the synovial fluid (SF) proteome could distinguish a subset of patients in whom disease extends to affect a large number of joints. Methods. SF samples from 57 patients were obtained around time of initial diagnosis of JIA, labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with expression verified by immunochemical methods. Protein glycosylation status was confirmed by hydrophilic interaction liquid chromatography. Results. A truncated isoform of vitamin D binding protein (VDBP) is present at significantly reduced levels in the SF of oligoarticular patients at risk of disease extension, relative to other subgroups (p < 0.05). Furthermore, sialylated forms of immunopurified synovial VDBP were significantly reduced in extended oligoarticular patients (p < 0.005). Conclusion. Reduced conversion of VDBP to a macrophage activation factor may be used to stratify patients to determine risk of disease extension in JIA patients. PMID:22771520

  19. What Is Reactive Arthritis?

    MedlinePlus

    ... 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 ...

  20. Synovial distribution of “systemically” administered acetylsalicylic acid in the isolated perfused equine distal limb

    PubMed Central

    2013-01-01

    Background This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plasma concentrations obtained from literature. Salicylate concentrations in the joint were determined using microdialysis and high performance liquid chromatography (HPLC). Any anti-inflammatory effect of synovial ASA concentrations was assessed using an ASA EC50 (half maximal effective concentration) determined in equine whole blood. Results The ASA concentration in the synovial fluid (n = 6) reached a maximum of 4 μg/mL, the mean concentration over the entire perfusion period was 2 μg/mL. Maximum SA concentration was 17 μg/mL, the average was 14 μg/mL. ASA and SA concentration in the synovial fluid exceeded systemic concentrations 2 h and 3.5 h after “systemic” administration, respectively. Conclusions ASA and SA accumulated in the in the synovial fluid of the ex vivo model despite decreasing systemic concentrations. This suggests a prolonged anti-inflammatory effect within the joint that remains to be further elucidated. PMID:23531229

  1. [Therapeutic options for synovial sarcoma].

    PubMed

    Deme, Dániel; Telekes, András

    2015-05-31

    Synovial sarcomas account for approximately 5 to 10% of soft tissue sarcomas and 0.05 to 0.1% of all malignant neoplasms. They predominantly affect the extremities but can occur in any part of the body. More than 50% of the patients are expected to develop metastatic disease within 3-5 years. In some patients disease recurrence may develop after 20 years. The 5-year overall survival rate is 10% for patients with metastatic disease and 76% for patients with localized one. Age, tumour size, histological subtype, and adjuvant radiotherapy influence prognosis. The role of adjuvant chemotherapy has not been proven yet. There are several ongoing clinical trials to determine the efficacy of active agents used for therapy of locally advanced, relapsed/refractory or metastatic disease. Better understanding of the biological behaviour of synovial sarcomas would provide the future way for the targeted therapy in combination with conventional treatments. PMID:26004546

  2. Synovial sarcoma of the foot.

    PubMed

    Bekarev, Mikhail; Elsinger, Elisabeth C; Villanueva-Siles, Esperanza; Borzykowski, Ross M; Geller, David S

    2013-01-01

    We report the case of a 75-year-old male who underwent lung lobectomy for presumed lung cancer. Thereafter, he presented with a painful mass between the third and fourth metatarsal heads in the foot that was assumed to be Morton's neuroma. After extensive oncologic evaluation, the foot mass was diagnosed as a synovial sarcoma. In retrospect, his lung lesion was understood to be metastatic disease. PMID:23632071

  3. Contribution of TNFalpha, IL-1beta and CINC-1 for articular incapacitation, edema and cell migration in a model of LPS-induced reactive arthritis.

    PubMed

    Bressan, Elisângela; Cunha, Fernando De Queiroz; Tonussi, Carlos Rogério

    2006-10-01

    The protective effect of anti-CINC-1, -TNFalpha and -IL-1beta antisera on articular inflammatory incapacitation, articular diameter and synovial fluid cell content, which are correlated to nociception, edema and cell migration, respectively, were evaluated in a rat model of LPS-induced reactive arthritis. In this model, Escherichia coli lipopolysaccharide (LPS; 30 ng) was injected in a knee-joint previously primed with carrageenan (300 microg). Articular incapacitation was evaluated hourly by the automated registering of the knee-joint function during animal walking, and the knee-joint edema was evaluated by measuring the articular diameter increase. After 6 h, the animals were euthanized for collecting synovial fluid for the evaluation of cell migration. LPS produced dose-dependent incapacitation and edema. Anti-TNFalpha, -IL-1beta, and -CINC-1 antisera (20 and 40 microl) were used as pretreatment into knee-joint before LPS injection. At higher dose, Anti-TNFalpha and anti-CINC-1 were able to inhibit incapacitation, articular edema and mononuclear (MON) migration. Anti-IL1beta did not affect incapacitation at any dose, although inhibited edema and cell migration. Surprisingly, the higher dose of anti-IL1beta antisera did not inhibit cell migration, although inhibited articular edema. These findings corroborate the role TNFalpha has in different forms of arthritis, but points out the idea that CINC-1 (the homologue for human IL-8) may constitute a promising target for reactive arthritis management. Indeed, the potent antiedematogenic effect, and principally the anti-migration effect of anti-CINC-1, raises the possibility of a better control of disease progression than with anti-IL-1beta therapies. PMID:17166735

  4. Chemokines and chemokine receptors in arthritis

    PubMed Central

    Szekanecz, Zoltan; Vegvari, Aniko; Szabo, Zoltan; Koch, Alisa E.

    2010-01-01

    Chemokines are involved in leukocyte recruitment to inflammatory sites, such as the synovial tissue in rheumatoid arthritis (RA). There is a structural and a functional classification of chemokines. The former includes four groups: CXC, CC, C and CX3C chemokines. Chemokines may also be either inflammatory or homeostatic, however, these functions often overlap. Anti-chemokine and anti-chemokine receptor targeting may be therapeutically used in the future biological therapy of arthritis. Most data in this field have been obtained from animal models of arthritis as only very few human RA trials have been completed. However, it is very likely that various specific chemokine and chemokine receptor antagonists will be developed and administered to RA patients. PMID:20036936

  5. Glycosaminoglycan concentration in synovium and other tissues of rabbit knee in relation to synovial hydraulic resistance.

    PubMed Central

    Price, F M; Levick, J R; Mason, R M

    1996-01-01

    1. The hydraulic resistance of the synovial lining of a joint, a key coupling coefficient in synovial fluid turnover, is thought to depend on the concentration of biopolymers (glycosaminoglycans (GAGs) and collagen) in the synovial intercellular spaces, because these polymers create hydraulic drag. The primary aim of this study was to obtain microscopically separated, milligram samples of the very thin synovium from eight rabbit knees, and to analyse these quantitatively for GAGs (chondroitin sulphate, heparan sulphate and hyaluronan) and collagen to allow comparison with published hydraulic resistance data. Synovial fluid and femoral cartilage were also studied. 2. Synovium comprised 73 +/- 3% water by weight (mean +/- S.E.M.). Of the 270 mg solid per gram of wet tissue, protein formed 136 mg (by automated amino acid analysis), and of this 94 mg was collagen by hydroxyproline analysis. From the collagen mass and fibril volume fraction (0.153 of tissue by morphometry), fibrillar specific volume was calculated to be 1.43 ml per gram of molecular collagen, and fibril water content 47% by volume. 3. The concentration of chondroitin 4-sulphate (C4S) plus chondroitin 6-sulphate (C6S), measured by capillary zone electrophoresis was 0.55 mg per gram of synovium--much greater than in synovial fluid (0.04 mg g-1) and much less than in cartilage (27.8 mg g-1). The C4S/C6S ratio in synovium (7.3) differed from that in cartilage (0.7), indicating that different proteoglycans predominated in synovium. The heparan sulphate concentration, assayed by radioactive Ruthenium Red binding, was 0.92 mg per gram of synovium (synovial fluid, 0.08 mg g-1; cartilage, 0.72 mg g-1). 4. In contrast to sulphated GAGs, the hyaluronan concentration was highest in synovial fluid (3.53 mg g-1; biotinylated G1 domain binding assay). The concentration in synovial interstitium was only 0.56 mg g-1 (corrected for interstitial volume fraction, 0.66), even though there is open contact between synovial

  6. TNFα promotes Th17 cell differentiation through IL-6 and IL-1β produced by monocytes in rheumatoid arthritis.

    PubMed

    Zheng, Yingxia; Sun, Lei; Jiang, Ting; Zhang, Dongqing; He, Dongyi; Nie, Hong

    2014-01-01

    TNFα plays an important role in autoimmune pathogenesis and is the main therapeutic target of rheumatoid arthritis. However, its underlying mechanism is not completely understood. In this study, we described that Th17 cells were accumulated in synovial fluid, which was attributable to TNFα aberrantly produced in rheumatoid synovium. Interestingly, TNFα cannot induce IL-17 production of CD4(+) T cells directly, but through the monocytes high levels of IL-1β and IL-6 in a TNFRI and TNFRII dependent manner from the active RA patients are produced. TNFα was shown to enhance the phosphorylation level of STAT3 and the expression level of transcription factor RORC of CD4(+) T cells when cultured with CD14(+) monocytes. Treatment with an approved TNFα blocking antibody showed marked reduction in the levels of IL-6, IL-1β, and IL-17 and the expression level of STAT3 phosphorylation in relation to Th17 cell differentiation in patients with rheumatoid arthritis. The study provides new evidence supporting the critical role of TNFα in the pathogenic Th17 cell differentiation in rheumatoid arthritis. PMID:25436214

  7. A new phenylpyrazoleanilide, y-320, inhibits interleukin 17 production and ameliorates collagen-induced arthritis in mice and cynomolgus monkeys.

    PubMed

    Ushio, Hiroyuki; Ishibuchi, Seigo; Oshita, Koichi; Seki, Noriyasu; Kataoka, Hirotoshi; Sugahara, Kunio; Adachi, Kunitomo; Chiba, Kenji

    2013-01-01

    Interleukin (IL)-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320, a new phenylpyrazoleanilide immunomodulator. Y-320 inhibited IL-17 production by CD4 T cells stimulated with IL-15 with IC50 values of 20 to 60 nM. Oral administration of Y-320 (0.3 to 3 mg/kg) significantly inhibited the development and progression of arthritis and joint destruction with reduction of IL-17 mRNA expression in arthritic joints of type II collagen-induced arthritis (CIA) in DBA/1J mice. Y-320 in combination with anti-murine tumor necrosis factor-α monoclonal antibody showed a synergistic effect on mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally) ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, an orally active inhibitor for IL-17 production, provides a useful therapy for RA. PMID:24366113

  8. Macrophages - silent enemies in juvenile idiopathic arthritis.

    PubMed

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

    2016-01-01

    The inflammatory response by secretion of cytokines and other mediators is postulated as one of the most significant factors in the pathophysiology of juvenile idiopathic arthritis (JIA). The effect of macrophage action depends on the type of their activation. Classically activated macrophages (M1) are responsible for release of molecules crucial for joint inflammation. Alternatively activated macrophages (M2) may recognize self antigens by scavenger receptors and induce the immunological reaction leading to autoimmune diseases such as JIA. Molecules essential for JIA pathophysiology include: TNF-α, the production of which precedes synovial inflammation in rheumatoid arthritis; IL-1 as a key mediator of synovial damage; chemotactic factors for macrophages IL-8 and MCP-1; IL6, the level of which correlates with the radiological joint damage; MIF, promoting the secretion of TNF-α and IL-6; CCL20 and HIF, significant for the hypoxic synovial environment in JIA; GM-CSF, stimulating the production of macrophages; and IL-18, crucial for NK cell functions. Recognition of the role of macrophages creates the potential for a new therapeutic approach. PMID:27383571

  9. Antiarthritis Effect of Morin is Associated with Inhibition of Synovial Angiogensis.

    PubMed

    Zeng, Ni; Tong, Bei; Zhang, Xinyu; Dou, Yannong; Wu, Xin; Xia, Yufeng; Dai, Yue; Wei, Zhifeng

    2015-12-01

    Morin, a flavonoid isolated from Morus alba L. (Moraceae), possesses anti-inflammatory, antiangiogenic among other biological activities. This study investigated its effect on type II collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms in view of synovial angiogenesis. Morin administered po attenuated arthritic progression as indicated by reduction of arthritis scores and paw swelling. It also markedly reduced serum levels of the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), but increased the level of anti-inflammatory cytokine interleukin-10, and ameliorated histopathological changes of joints. Morin markedly inhibited expression of CD31, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor in synovial membrane tissues, and decreased serum levels of VEGF in CIA rats. In vitro, morin markedly inhibited VEGF-induced migration and tube formation in human umbilical vein endothelial cells. These results indicate that morin had antirheumatoid potential, and its mechanism might be associated with inhibition of synovial angiogenesis. PMID:26769128

  10. Reactive arthritis

    MedlinePlus

    Reactive arthritis is a group of conditions that may involve the joints, eyes, and urinary and genital systems. ... The exact cause of reactive arthritis is unknown. It occurs most often in men younger than age 40. It may follow an infection in the urethra ...

  11. Intimal lining layer macrophages but not synovial sublining macrophages display an IL-10 polarized-like phenotype in chronic synovitis

    PubMed Central

    2012-01-01

    Introduction Synovial tissue macrophages play a key role in chronic inflammatory arthritis, but the contribution of different macrophage subsets in this process remains largely unknown. The main in vitro polarized macrophage subsets are classically (M1) and alternatively (M2) activated macrophages, the latter comprising interleukin (IL)-4 and IL-10 polarized cells. Here, we aimed to evaluate the polarization status of synovial macrophages in spondyloarthritis (SpA) and rheumatoid arthritis (RA). Methods Expression of polarization markers on synovial macrophages, peripheral blood monocytes, and in vitro polarized monocyte-derived macrophages from SpA versus RA patients was assessed by immunohistochemistry and flow cytometry, respectively. The polarization status of the intimal lining layer and the synovial sublining macrophages was assessed by double immunofluorescence staining. Results The expression of the IL-10 polarization marker cluster of differentiation 163 (CD163) was increased in SpA compared with RA intimal lining layer, but no differences were found in other M1 and M2 markers between the diseases. Furthermore, no significant phenotypic differences in monocytes and in vitro polarized monocyte-derived macrophages were seen between SpA, RA, and healthy controls, indicating that the differential CD163 expression does not reflect a preferential M2 polarization in SpA. More detailed analysis of intimal lining layer macrophages revealed a strong co-expression of the IL-10 polarization markers CD163 and cluster of differentiation 32 (CD32) but not any of the other markers in both SpA and RA. In contrast, synovial sublining macrophages had a more heterogeneous phenotype, with a majority of cells co-expressing M1 and M2 markers. Conclusions The intimal lining layer but not synovial sublining macrophages display an IL-10 polarized-like phenotype, with increased CD163 expression in SpA versus RA synovitis. These differences in the distribution of the polarized

  12. The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis

    PubMed Central

    van Baarsen, L G M; de Hair, M J H; Ramwadhdoebe, T H; Zijlstra, IJ A J; Maas, M; Gerlag, D M; Tak, P P

    2013-01-01

    Objectives Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown aetiology. Recent work has shown that systemic autoimmunity precedes synovial inflammation, and animal models have suggested that changes in the lymph nodes may precede those in the synovial tissue. Therefore, we investigated the cellular composition of the lymph node in the earliest phases of inflammatory arthritis. Methods Thirteen individuals positive for immunoglobulin M (IgM) rheumatoid factor and/or anticitrullinated protein antibodies without arthritis were included. Additionally, we studied 14 early arthritis patients (arthritis duration ≤6 months, naïve for disease-modifying antirheumatic drugs), and eight healthy controls. All subjects underwent ultrasound-guided inguinal lymph node biopsy. Different T- and B-lymphocyte subsets were analysed by multicolour flow cytometry. Results There was an increase in activated CD69 CD8 T cells and CD19 B cells in early arthritis patients compared with healthy controls. We also observed a trend towards increased CD19 B cells in autoantibody-positive individuals without arthritis compared with healthy controls. Conclusions This exploratory study suggests that there is increased immune cell activation within lymph nodes of early arthritis patients as well as in autoantibody-positive individuals at risk of developing RA. This method provides a unique tool to investigate immunological changes in the lymph node compartment in the earliest phases of inflammatory arthritis. PMID:23661491

  13. Cultured human synovial fibroblasts rapidly metabolize kinins and neuropeptides.

    PubMed Central

    Bathon, J M; Proud, D; Mizutani, S; Ward, P E

    1992-01-01

    Kinins and substance P have been implicated in the pathogenesis of inflammatory arthritis by virtue of their abilities to induce vasodilation, edema, and pain. The relative biological potencies of these peptides in vivo would depend at least in part upon their rates of catabolism in the joint. We hypothesized that human synovial lining cells may regulate intraarticular levels of kinins and neuropeptides via degradation by cell surface-associated peptidases. We exposed intact human synovial fibroblasts to kinins and substance P, in the presence or absence of specific peptidase inhibitors, and measured the amount of intact substrate remaining and degradation product(s) generated over time. Aminopeptidase M (AmM; EC 3.4.11.2), neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11), and dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) were identified on the cell surface of synovial cells. Bradykinin degradation was due entirely to NEP-24.11 (1.39 +/- 0.29 nmol/min per well). Lysylbradykinin was also degraded by NEP-24.11 (0.80 +/- 0.19 nmol/min per well); however, in the presence of phosphoramidon, AmM-mediated conversion to bradykinin (3.74 +/- 0.46 nmol/min per well) could be demonstrated. The combined actions of NEP-24.11 (0.93 +/- 0.15 nmol/min per well) and DAP IV (0.84 +/- 0.18 nmol/min per well) were responsible for the degradation of substance P. AmM (2.44 +/- 0.33 nmol/min per well) and NEP-24.11 (1.30 +/- 0.45 nmol/min per well) were responsible for the degradation of the opioid peptide, [Leu5]enkephalin. The identity of each of the three peptidases was confirmed via synthetic substrate hydrolysis, inhibition profile, and immunological identification. The profiles of peptidase enzymes identified in cells derived from rheumatoid and osteoarthritic joints were identical. These data demonstrate the human synovial fibroblast to be a rich source of three specific peptidases and suggest that it may play a prominent role in regulating peptide levels in the joint

  14. Synovial Sarcoma Mimicking Myositis Ossificans

    PubMed Central

    Erkut, Adem; Guvercin, Yılmaz; Bedir, Recep

    2016-01-01

    A calcification mass was incidentally found in the soft tissue of a patient who had a history of trauma to the extremity during examination. The patient had no symptom. The pathological analysis of the mass revealed it was an early-phase synovial sarcoma (SS). The diagnosis was made before the onset of symptoms and proper surgical intervention was performed. Therefore, in case of a <1 cm lesion clinically suspicious of myositis ossificans, SS should be taken into consideration as a possible diagnosis. PMID:27595081

  15. Synovial Sarcoma Mimicking Myositis Ossificans.

    PubMed

    Balik, Mehmet Sabri; Erkut, Adem; Guvercin, Yılmaz; Bedir, Recep

    2016-09-01

    A calcification mass was incidentally found in the soft tissue of a patient who had a history of trauma to the extremity during examination. The patient had no symptom. The pathological analysis of the mass revealed it was an early-phase synovial sarcoma (SS). The diagnosis was made before the onset of symptoms and proper surgical intervention was performed. Therefore, in case of a <1 cm lesion clinically suspicious of myositis ossificans, SS should be taken into consideration as a possible diagnosis. PMID:27595081

  16. The glycosylation of human synovial lubricin: implications for its role in inflammation.

    PubMed

    Estrella, Ruby P; Whitelock, John M; Packer, Nicolle H; Karlsson, Niclas G

    2010-07-15

    Acidic proteins were isolated from synovial fluid from two osteoarthritic and two rheumatoid arthritic patients and identified by MS. It was found that the most abundant protein in all of the samples was the mucin-like protein lubricin. Further characterization of lubricin from the different patients by LC (liquid chromatography)-MS of released oligosaccharides showed that the core 1 O-linked oligosaccharides NeuAc alpha2-3Gal beta1-3GalNAc and NeuAc alpha2-3Gal beta1-3(NeuAc alpha2-6)GalNAc were the dominating structures on lubricin. The latter was found to be more prevalent in the rheumatoid arthritis samples, indicating that sialylation is up-regulated as part of the inflammatory response. In addition to these dominating structures, core 2 structures were also found in low amounts, where the largest was the disialylated hexasaccharide corresponding to the sequence NeuAc alpha2-3Ga lbeta1-3(NeuAc alpha2-3Gal beta1-3/4GlcNAc beta1-6)GalNAc. It was also found that a small proportion of the core 2 oligosaccharides carried sulfate. The ability of lubricin to present complex glycosylation reflecting the state of the joint tissue makes lubricin a candidate as a carrier of inflammatory oligosaccharide epitopes. In particular, it was shown that lubricin from inflamed arthritic tissue was recognized by the antibody MECA-79 and thus carried the sulfated epitope proposed to be part of the L-selectin ligand that is responsible for recruitment of leucocytes to inflammatory sites. PMID:20443780

  17. Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells

    PubMed Central

    Onodera, Yuta; Teramura, Takeshi; Takehara, Toshiyuki; Shigi, Kanae; Fukuda, Kanji

    2015-01-01

    Oxidative stress within the arthritis joint has been indicated to be involved in generating mediators for tissue degeneration and inflammation. COX-2 is a mediator in inflammatory action, pain and some catabolic reactions in inflamed tissues. Here, we demonstrated a direct relationship between oxidative stress and Cox-2 expression in the bovine synovial fibroblasts. Furthermore, we elucidated a novel mechanism, in which oxidative stress induced phosphorylation of MAPKs and NF-κB through TAK1 activation and resulted in increased Cox-2 and prostaglandin E2 expression. Finally, we demonstrated that ROS-induced Cox-2 expression was inhibited by supplementation of an antioxidant such as N-acetyl cysteamine and hyaluronic acid in vitro and in vivo. From these results, we conclude that oxidative stress is an important factor for generation of Cox-2 in synovial fibroblasts and thus its neutralization may be an effective strategy in palliative therapy for chronic joint diseases. PMID:26110105

  18. Antibodies to Endothelial Cell Growth Factor and Obliterative Microvascular Lesions in Synovia of Patients with Antibiotic-Refractory Lyme Arthritis

    PubMed Central

    Londoño, Diana; Cadavid, Diego; Drouin, Elise E.; Strle, Klemen; McHugh, Gail; Aversa, John; Steere, Allen C.

    2014-01-01

    Objective Endothelial cell growth factor (ECGF) was recently identified as the first autoantigen known to be a target of T and B cell responses in about 20% of patients with antibiotic-refractory Lyme arthritis. The goal of the current study was to look for a pathologic correlate between ECGF autoantibody responses and histologic findings in synovial tissue. Methods Synovial tissue was examined from 14 patients with antibiotic-refractory Lyme arthritis and 6 patients with other forms of chronic inflammatory arthritis, primarily rheumatoid arthritis. The tissue sections were subjected to chemical and immunostaining, and IgG antibody responses to ECGF were determined by ELISA. Each finding was ranked for statistical analysis. Results In each disease, synovial tissue showed synovial hypertrophy, vascular proliferation, immune cell infiltrates, and fibrosis. However, among the 14 patients with antibiotic-refractory arthritis, 8 (57%) had obliterative microvascular lesions in the tissue compared with none of 6 patients with other forms of chronic inflammatory arthritis (P=0.04). Among the patients with Lyme arthritis, 5 (36%) had autoantibody responses to ECGF, and all 5 had obliterative lesions compared with only 3 of 9 patients who lacked ECGF antibody responses (P=0.009). Moreover, the magnitude of ECGF antibody responses correlated directly with the extent of obliterative lesions (P=0.02) and with greater vascularity in the tissue (P=0.05). Conclusions The correlations of ECGF autoantibody reactivity with obliterative microvascular lesions imply that these autoantibodies may be involved in the obliterative process, suggesting that anti-ECGF antibodies have specific pathologic consequences in synovial tissue in patients with antibiotic-refractory Lyme arthritis. PMID:24623727

  19. Reactive arthritis.

    PubMed

    Keat, A

    1999-01-01

    Reactive arthritis is one of the spondyloarthropathy family of clinical syndromes. The clinical features are those shared by other members of the spondyloarthritis family, though it is distinguished by a clear relationship with a precipitating infection. Susceptibility to reactive arthritis is closely linked with the class 1 HLA allele B27; it is likely that all sub-types pre-dispose to this condition. The link between HLA B27 and infection is mirrored by the development of arthritis in HLA B27-transgenic rats. In this model, arthritis does not develop in animals maintained in a germ-free environment. Infections of the gastrointestinal, genitourinary and respiratory tract appear to provoke reactive arthritis and a wide range of pathogens has now been implicated. Although mechanistic parallels may exist, reactive arthritis is distinguished from Lyme disease, rheumatic fever and Whipple's disease by virtue of the distinct clinical features and the link with HLA B27. As in these conditions both antigens and DNA of several micro-organisms have been detected in joint material from patients with reactive arthritis. The role of such disseminated microbial elements in the provocation or maintenance of arthritis remains unclear. HLA B27-restricted T-cell responses to microbial antigens have been demonstrated and these may be important in disease pathogenesis. The importance of dissemination of bacteria from sites of mucosal infection and their deposition in joints has yet to be fully understood. The role of antibiotic therapy in the treatment of reactive arthritis is being explored; in some circumstances, both the anti-inflammatory and anti-microbial effects of certain antibiotics appear to be valuable. The term reactive arthritis should be seen as a transitory one, reflecting a concept which may itself be on the verge of replacement, as our understanding of the condition develops. Nevertheless it appropriately describes arthritis that is associated with demonstrable

  20. Autoimmune response to transthyretin in juvenile idiopathic arthritis

    PubMed Central

    Clement, Cristina C.; Moncriefe, Halima; Lele, Aditi; Janow, Ginger; Becerra, Aniuska; Bauli, Francesco; Saad, Fawzy A.; Perino, Giorgio; Montagna, Cristina; Cobelli, Neil; Hardin, John; Stern, Lawrence J.; Ilowite, Norman; Porcelli, Steven A.; Santambrogio, Laura

    2016-01-01

    Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatological condition. Although it has been proposed that JIA has an autoimmune component, the autoantigens are still unknown. Using biochemical and proteomic approaches, we identified the molecular chaperone transthyretin (TTR) as an antigenic target for B and T cell immune responses. TTR was eluted from IgG complexes and affinity purified from 3 JIA patients, and a statistically significant increase in TTR autoantibodies was observed in a group of 43 JIA patients. Three cryptic, HLA-DR1–restricted TTR peptides, which induced CD4+ T cell expansion and IFN-γ and TNF-α production in 3 out of 17 analyzed patients, were also identified. Misfolding, aggregation and oxidation of TTR, as observed in the synovial fluid of all JIA patients, enhanced its immunogenicity in HLA-DR1 transgenic mice. Our data point to TTR as an autoantigen potentially involved in the pathogenesis of JIA and to oxidation and aggregation as a mechanism facilitating TTR autoimmunity. PMID:26973882

  1. T cell responses in psoriasis and psoriatic arthritis.

    PubMed

    Diani, Marco; Altomare, Gianfranco; Reali, Eva

    2015-04-01

    According to the current view the histological features of psoriasis arise as a consequence of the interplay between T cells, dendritic cells and keratinocytes giving rise to a self-perpetuating loop that amplifies and sustains inflammation in lesional skin. In particular, myeloid dendritic cell secretion of IL-23 and IL-12 activates IL-17-producing T cells, Th22 and Th1 cells, leading to the production of inflammatory cytokines such as IL-17, IFN-γ, TNF and IL-22. These cytokines mediate effects on keratinocytes thus establishing the inflammatory loop. Unlike psoriasis the immunopathogenic features of psoriatic arthritis are poorly characterized and there is a gap in the knowledge of the pathogenic link between inflammatory T cell responses arising in the skin and the development of joint inflammation. Here we review the knowledge accumulated over the years from the early evidence of autoreactive CD8 T cells that was studied mainly in the years 1990s and 2000s to the recent findings of the role of Th17, Tc17 cells and γδ T cells in psoriatic disease pathogenesis. The review will also focus on common and distinguishing features of T cell responses in psoriatic plaques and in synovial fluid of patients with psoriatic arthritis. The integration of this information could help to distinguish the role played by T cells in the initiation phase of the disease from the role of T cells as downstream effectors sustaining inflammation in psoriatic plaques and potentially leading to disease manifestation in distant joints. PMID:25445403

  2. Calcium pyrophosphate arthritis

    MedlinePlus

    ... disease that can cause attacks of arthritis. Like gout, crystals form in the joints. But in this ... CPPD arthritis can be confused with: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis Exams and Tests Most arthritic ...

  3. Calcium pyrophosphate arthritis

    MedlinePlus

    ... that can cause attacks of arthritis. Like with gout, crystals form in the joints. But in calcium ... pyrophosphate arthritis can be misdiagnosed as: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis

  4. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

  5. Rheumatoid arthritis

    MedlinePlus

    ... rheumatoid arthritis drugs. However, because they are very expensive, insurance approval is generally required. Most of them ... rich in fish oils (omega-3 fatty acids). Smoking cigarettes should be stopped. Excessive alcohol should also ...

  6. Enteropathic Arthritis

    MedlinePlus

    ... as well. Those who test positive for the HLA-B27 genetic marker are much more likely to have spinal involvement with enteropathic arthritis than those who test negative. Disease Course/Prognosis ...

  7. Septic arthritis

    MedlinePlus

    ... 2013:chap 109. Krogstad P. Septic arthritis. In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ. Feigin and Cherry's Textbook of Pediatric Infectious Diseases . 7th ed. Philadelphia, ...

  8. Gonococcal arthritis

    MedlinePlus

    ... people who have gonorrhea caused by the bacteria Neisseria gonorrhoeae . Gonococcal arthritis affects women more often than men. ... Saunders; 2013:chap 109. Marrazzo JM, Apicella MA. Neisseria gonorrhoeae (gonnorrhea). In: Bennett JE, Dolin R, Blaser MJ, ...

  9. Psoriatic arthritis

    MedlinePlus

    ... that often occurs with a skin condition called psoriasis . ... inflammatory condition. About 1 in 20 people with psoriasis may develop arthritis with the skin condition. In most cases, psoriasis ...

  10. Reactive Arthritis

    MedlinePlus

    ... with treatment and may cause joint damage. What Research Is Being Conducted on Reactive Arthritis? Researchers continue ... such as methotrexate and sulfasalazine. More information on research is available from the following websites: National Institutes ...

  11. Psoriatic arthritis

    MedlinePlus

    ... that often occurs with a skin condition called psoriasis . Causes Psoriasis is a common skin problem that causes red ... inflammatory condition. About 1 in 20 people with psoriasis may develop arthritis with the skin condition. In ...

  12. The Features of the Synovium in Early Rheumatoid Arthritis According to the 2010 ACR/EULAR Classification Criteria

    PubMed Central

    van de Sande, Marleen G. H.; de Hair, Maria J. H.; Schuller, Yvonne; van de Sande, Gijs P. M.; Wijbrandts, Carla A.; Dinant, Huib J.; Gerlag, Danielle M.; Tak, Paul P.

    2012-01-01

    Objectives It has been shown in early arthritis cohorts that the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) enable an earlier diagnosis, perhaps at the cost of a somewhat more heterogeneous patient population. We describe the features of synovial inflammation in RA patients classified according to these new criteria. Methods At baseline, synovial tissue biopsy samples were obtained from disease-modifying antirheumatic drug (DMARD)-naïve early RA patients (clinical signs and symptoms <1 year). Synovial tissue was analyzed for cell infiltration, vascularity, and expression of adhesion molecules. Stained sections were evaluated by digital image analysis. Patients were classified according to the two different sets of classification criteria, autoantibody status, and outcome. Findings Synovial tissue of 69 RA patients according to 2010 ACR/EULAR criteria was analyzed: 56 patients who fulfilled the criteria for RA at baseline and 13 who were initially diagnosed as undifferentiated arthritis but fulfilled criteria for RA upon follow up. The synovium at baseline was infiltrated by plasma cells, macrophages, and T cells as well as other cells, and findings were comparable to those when patients were selected based on the 1987 ACR criteria for RA. There was no clear cut difference in the characteristics of the synovium between RA patients initially diagnosed as undifferentiated arthritis and those who already fulfilled classification criteria at baseline. Conclusion The features of synovial inflammation are similar when the 2010 ACR/EULAR classification criteria are used compared to the 1987 ACR criteria. PMID:22574210

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

    PubMed Central

    Singh, Sachin Kumar; Gulati, Monica

    2014-01-01

    The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease modifying antirheumatic drugs (DMARDs), and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology. PMID:24688450

  14. Application of liposomes in treatment of rheumatoid arthritis: quo vadis.

    PubMed

    Kapoor, Bhupinder; Singh, Sachin Kumar; Gulati, Monica; Gupta, Reena; Vaidya, Yogyata

    2014-01-01

    The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease modifying antirheumatic drugs (DMARDs), and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology. PMID:24688450

  15. [Genetics and genomics in rheumatoid arthritis (RA): An update].

    PubMed

    Rodríguez-Elías, Ana Karen; Maldonado-Murillo, Karina; López-Mendoza, Luis Fernando; Ramírez-Bello, Julián

    2016-01-01

    Rheumatoid arthritis is a chronic inflammatory autoimmune disease that affects approximately 0.5-1% of the general population and leads to chronic synovial inflammation, destruction of cartilage and bone, and disability. The heritability of rheumatoid arthritis has been estimated to be about 60%, while the contribution of HLA to heritability has been estimated to be 11-37%. Other genes, such as PTPN22, STAT4, CTLA4, TRAF1, PADI4, IRF5, FCRL3, TNFIP3, TNF-α, miRNAs, CD28, CD40, TYK2, etc., have been associated with susceptibility, severity, activity, and treatment response of rheumatoid arthritis. The aim of this review is to describe the role of gene variants located in immune system genes associated with susceptibility to rheumatoid arthritis. PMID:27160622

  16. Viral arthritis.

    PubMed

    Marks, Michael; Marks, Jonathan L

    2016-04-01

    Acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. A viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. The epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. A travel history therefore forms an important part of the assessment of patients presenting with an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the alphaviruses are among the most important causes of virally mediated arthritis. Targeted serological testing may be of value in establishing a diagnosis, and clinicians must also be aware that low-titre autoantibodies, such as rheumatoid factor and antinuclear antibody, can occur in the context of acute viral arthritis. A careful consideration of epidemiological, clinical and serological features is therefore required to guide clinicians in making diagnostic and treatment decisions. While most virally mediated arthritides are self-limiting some warrant the initiation of specific antiviral therapy. PMID:27037381

  17. Pathogenesis of rheumatoid arthritis and the immune response

    SciTech Connect

    Scheinberg, M.A.

    1983-08-01

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

  18. Bursal synovial chondromatosis formation following osteochondroma resection.

    PubMed

    Lin, Yu-Ching; Goldsmith, Jeffrey D; Gebhardt, Mark G; Wu, Jim S

    2014-07-01

    Osteochondroma is a common tumor of the bone and can be complicated by adventitial bursa formation and malignant transformation of the cartilaginous cap. Synovial chondromatosis formation within these bursae is extremely rare and can be confused with malignant transformation of the osteochondroma cap to a chondrosarcoma. We describe a case of extra-articular synovial chondromatosis formation several years following osteochondroma resection. Cartilage nodule formation within the bursal synovial lining and proliferation of cartilage debris shed from the cartilaginous cap during surgery or biopsy are potential etiologies of this rare complication of osteochondromas. PMID:24453028

  19. SYNOVIAL GIANT CELL TUMOR OF THE KNEE

    PubMed Central

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

    2015-01-01

    Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection. PMID:27004193

  20. Rheumatoid arthritis as a hyper-endoplasmic-reticulum-associated degradation disease.

    PubMed

    Yamasaki, Satoshi; Yagishita, Naoko; Tsuchimochi, Kaneyuki; Nishioka, Kusuki; Nakajima, Toshihiro

    2005-01-01

    We introduce Synoviolin as a novel pathogenic factor in rheumatoid arthritis (RA). Experimental studies indicate that this endoplasmic reticulum (ER)-resident E3 ubiquitin ligase has important functions in the ER-associated degradation (ERAD) system, an essential system for ER homeostasis. Overexpression of Synoviolin in mice causes arthropathy with synovial hyperplasia, whereas heterozygous knockdown results in increased apoptosis of synovial cells and resistance to collagen-induced arthritis in mice. On the basis of these experimental data, we propose that excess elimination of unfolded proteins (that is, 'hyper-ERAD') by overexpression of Synoviolin triggers synovial cell overgrowth and hence a worsening of RA. Further analysis of the hyper-ERAD system may permit the complex pathomechanisms of RA to be uncovered. PMID:16207344

  1. Arthritis associated with adjuvant mycobacterial treatment for carcinoma of the bladder.

    PubMed Central

    Hughes, R A; Allard, S A; Maini, R N

    1989-01-01

    A patient who developed an inflammatory polyarthritis following intravesical administration of bacillus Calmette-Guérin (BCG) used in the treatment of bladder cancer is described. An inflammatory synovitis comprising predominantly T lymphocytes was demonstrated on synovial biopsy. The synovitis resolved spontaneously within 14 days in this 'human model' of adjuvant arthritis. Images PMID:2786389

  2. Clonal dominance among T-lymphocyte infiltrates in arthritis

    SciTech Connect

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

    1988-02-01

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

  3. Features of the Synovium of Individuals at Risk of Developing Rheumatoid Arthritis

    PubMed Central

    de Hair, MJH; van de Sande, MGH; Ramwadhdoebe, TH; Hansson, M; Landewé, R; van der Leij, C; Maas, M; Serre, G; van Schaardenburg, D; Klareskog, L; Gerlag, DM; van Baarsen, LGM; Tak, PP

    2014-01-01

    Objective Findings from previous studies have suggested that subclinical inflammation of the synovium does not coincide with the appearance of rheumatoid arthritis (RA)–specific autoantibodies. This study was undertaken to examine the relationship between the presence of autoantibodies, changes in the synovium, and development of arthritis over time in a markedly larger, prospective study. Methods Fifty-five individuals who were IgM rheumatoid factor positive and/or anti–citrullinated protein antibody (ACPA) positive (detected by the anti–cyclic citrullinated peptide antibody test) and who were without any evidence of arthritis upon physical examination were included in the study. ACPAs were subsequently also detected using a multiplex chip-based assay. All individuals underwent magnetic resonance imaging and mini-arthroscopic synovial biopsy sampling of a knee joint at inclusion and were prospectively followed up. Proportional hazards regression analysis was performed to investigate whether changes in the synovium were associated with the onset of arthritis. Results Fifteen individuals (27%) developed arthritis after a median followup time of 13 months (interquartile range 6–27 months; range 1–47 months). No overt synovial inflammation was observed, but CD3+ T cell numbers in the biopsy tissue showed a borderline association with subsequent development of clinically manifest arthritis (hazard ratio 2.8, 95% confidence interval [95% CI] 0.9–9.1; P = 0.088). In addition, the presence of CD8+ T cells was associated with ACPA positivity (odds ratio [OR] 16.0, 95% CI 1.7–151.1) and with the total number of ACPAs present (OR 1.4, 95% CI 1.0–1.8). Conclusion These findings confirm and extend previous results showing the absence of clearcut synovial inflammation in individuals having systemic autoimmunity associated with RA. However, subtle infiltration by synovial T cells may precede the signs and symptoms of arthritis in preclinical RA. PMID:24574210

  4. Bone scintigraphic demonstration of synovial chondromatosis

    SciTech Connect

    Smith, R.; Hulsey, J.M.

    1987-02-01

    Markedly increased periarticular Tc-99m diphosphonate uptake around the knee is described in a patient found to have synovial chondromatosis. The pathophysiology and possible causes of bone tracer uptake in this cartilaginous disorder are discussed.

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

    PubMed Central

    Newsum, Elize C.; Maijer, Karen I.; van de Sande, Marleen G. H.; Ramwadhdoebe, Tamara H.; van Schaardenburg, Dirkjan; van Baarsen, Lisa G. M.; Korotkova, Marina; Gerlag, Danielle M.; Tak, Paul-Peter; Jakobsson, Per-Johan

    2015-01-01

    Objective Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA). A major pathway involved in pain is the prostaglandin (PG) E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients. Methods Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) with arthralgia (n=15) and/or a positive family history of RA (n=8), who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug naïve) who after 2 years follow up fulfilled classification criteria for RA (n=63), spondyloarthritis (SpA; n=14), or had unclassified arthritis (UA; n=27). In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH). Results In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals). However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients. Conclusion Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease. PMID:26225917

  6. Uncalcified Synovial Chondromatosis in the Pisotriquetral Joint.

    PubMed

    Kim, Hyo-Kon; Ha, Sung-Han; Lee, Gi-Jun; Yu, Sun-O; Kim, Jung-Rae

    2015-09-01

    Synovial chondromatosis is a rare lesion in the wrist, but some cases in the distal radioulnar joint have been reported and previous case reports emphasize joint calcifications, shown on preoperative plain radiographs. We report an extremely uncommon case of synovial chondromatosis in the pisotriquetral joint, in which radiographs and magnetic resonance imaging did not demonstrate apparent calcified bodies. In our case, for the accurate diagnosis and treatment, surgical exploration of the joint and synovectomy with removal of loose bodies was performed. PMID:26330969

  7. Odyssey of an elbow synovial chondromatosis.

    PubMed

    Sachinis, Nikolaos P; Sinopidis, Chris; Baliaka, Aggeliki; Givissis, Panagiotis

    2015-01-01

    Synovial chondromatosis of the elbow is an uncommon condition. However, a chondrosarcoma arising from the former is remarkably rare. The authors report a case of an elbow chondrosarcoma secondary to synovial chondromatosis in a 38-year-old woman. Before the development of chondrosarcoma, the patient underwent 3 operations and 3 sessions of radiosynovectomy because of continuous recurrence of synovial chondromatosis on the left elbow. After the last radiosynovectomy, magnetic resonance imaging and biopsy showed a grade II chondrosarcoma secondary to synovial chondromatosis. The patient underwent further surgery and custom-made arthroplasty because of aseptic loosening of the prosthesis. Four months after the last intervention, 3 subcutaneous nodes appeared on the patient's elbow and were histologically found to be a recurrence of chondrosarcoma (grade III). Amputation by disarticulation of the shoulder was performed in addition to biopsy of another subcutaneous node on the abdomen. The biopsy showed metastasis of chondrosarcoma. At final follow-up, the patient had lung metastasis 7 years after the initial diagnosis. A reason for the manifestation of primary synovial chondromatosis and its progression to chondrosarcoma has not been found. Synovial chondromatosis progressing to chondrosarcoma in the elbow was reported in only 1 case, with no clear initial diagnosis. The role of radiosynovectomy in the development of chondrosarcoma is unknown, and no reports have described the treatment of elbow synovial chondromatosis. Although synovial chondromatosis is benign, its metaplastic nature is a marker of possible malignancy, especially with signs of recurrence and aggression. The role of radiosynovectomy in malignant changes should be examined in future studies. PMID:25611422

  8. Articular synovial chondromatosis of the finger.

    PubMed

    Sano, Kazufumi; Hashimoto, Tomohisa; Kimura, Kazumasa; Ozeki, Satoru

    2014-10-01

    A 40-year-old woman presented with a six-month history of synovial chondromatosis of the metacarpophalangeal joint of the right ring finger, which was resected through both dorsal and volar incisions. To our knowledge there have been only 17 reported cases of articular synovial chondromatosis of the digital joint so far. We present a case affecting the metacarpophalangeal joint with a review of scattered information found in other 17 reports. PMID:23596991

  9. Uncalcified Synovial Chondromatosis in the Pisotriquetral Joint

    PubMed Central

    Kim, Hyo-Kon; Lee, Gi-Jun; Yu, Sun-O; Kim, Jung-Rae

    2015-01-01

    Synovial chondromatosis is a rare lesion in the wrist, but some cases in the distal radioulnar joint have been reported and previous case reports emphasize joint calcifications, shown on preoperative plain radiographs. We report an extremely uncommon case of synovial chondromatosis in the pisotriquetral joint, in which radiographs and magnetic resonance imaging did not demonstrate apparent calcified bodies. In our case, for the accurate diagnosis and treatment, surgical exploration of the joint and synovectomy with removal of loose bodies was performed. PMID:26330969

  10. Cubital Tunnel Syndrome, Associated With Synovial Chondromatosis

    PubMed Central

    Kim, Chang-Hwan; Kim, Min-Soo; Chang, Chul-Hoon

    2008-01-01

    A 62-year-old female patient suffered from numbness and resting pain in the right ring and little fingers for 3 years. We confirmed cubital tunnel syndrome with electrodiagnostic study and performed the operation. We found seven firm consistent nodules, compressing the overlying the ulnar nerve, proximal to the medial epicondyle in the operation field. Histological finding showed synovial chondromatosis. We report a rare case of a patient with cubital tunnel syndrome caused by synovial chondromatosis. PMID:19096614

  11. Induction of lyme arthritis in LSH hamsters

    SciTech Connect

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

    1988-09-01

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

  12. Imaging in Foot and Ankle Arthritis.

    PubMed

    Wilkinson, Victoria H; Rowbotham, Emma L; Grainger, Andrew J

    2016-04-01

    The foot and ankle are commonly involved in a range of arthritides that affect the joints, bones, and soft tissues. Accurate plain film interpretation can often aid the diagnosis and monitor disease progression and treatment response. Ultrasound and MRI afford superior depiction of the soft tissues, and advances over recent years have centered on early detection of synovitis, enabling earlier diagnosis and treatment. Advantages and disadvantages of the imaging techniques of radiography, multidetector computed tomography, ultrasound, and MRI are discussed, as is optimization of these modalities for the assessment of the anatomically complex joints of the foot and ankle. Diagnostic features enabling differentiation between rheumatoid arthritis, seronegative spondyloarthropathies, osteoarthritis, gout, crystal deposition disease, pigmented villonodular synovitis, Charcot arthropathy, septic arthritis, synovial osteochondromatosis, hemophilia, and reflex sympathetic dystrophy are also reviewed. PMID:27336451

  13. Collagenase in synovitis of rheumatoid arthritis.

    PubMed

    Sorsa, T; Konttinen, Y T; Lindy, O; Ritchlin, C; Saari, H; Suomalainen, K; Eklund, K K; Santavirta, S

    1992-08-01

    There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue. PMID:1411581

  14. Performance of the Existing Classification Criteria for Gout in Thai Patients Presenting With Acute Arthritis

    PubMed Central

    Jatuworapruk, Kanon; Lhakum, Panomkorn; Pattamapaspong, Nuttaya; Kasitanon, Nuntana; Wangkaew, Suparaporn; Louthrenoo, Worawit

    2016-01-01

    Abstract Currently, there are 5 existing classification criteria for gout: the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria. This study was carried out to determine the performance of these classification criteria in Thai patients presenting with acute arthritis. All consecutive patients presenting with acute arthritis and being consulted at the Rheumatology Unit, Chiang Mai University Hospital from January 2013 to May 2015 were invited to join the study. Gout was defined by the presence of monosodium urate crystals in the synovial fluid or tissue examined by experienced rheumatologists. The 5 existing gout classification criteria were performed and evaluated in all of the patients, who were divided in subgroups of early disease (≤2 years), established disease (>2 years), and those without tophus. There were 136 gout and 97 nongout patients. Sensitivity and specificity across all criteria ranged from 75.7% to 97.1% and 68.0% to 84.5%, respectively. Overall, the Mexico criteria had the highest sensitivity (97.1%), and the ARA survey criteria the highest specificity (84.5%), whereas the Mexico criteria performed well in early disease with sensitivity and specificity of 97.1% and 81.7%, respectively. All 5 criteria showed high sensitivity (from 76.4% to 99.1%) but low specificity (from 30.8% to 65.4%) in established disease. In patients without tophus, the sensitivity and specificity ranged from 64.1% to 95.7% and 68.8% to 85.4%, respectively. The ARA survey criteria across all groups showed consistently high specificity for gout. The 5 existing classification criteria for gout had limited sensitivity and specificity in Thai patients presenting with acute arthritis. The ARA survey criteria are the most suitable for diagnosing gout in Thai people when crystal identification is not available. PMID:26844519

  15. Growth-related gene product {alpha}: A chemotactic cytokine for neutrophils in rheumatoid arthritis

    SciTech Connect

    Koch, A.E.; Pope, R.M. |; Shah, M.R.; Hosaka, S.

    1995-10-01

    Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product {alpha} (gro{alpha}) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro{alpha} (mean 5.3 {+-} 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro{alpha} (mean 4.3 {+-} 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10{sup 5}/cells/ml RPMI 1640/24 h) produced antigenic gro{alpha} (mean 0.2 {+-} 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-{alpha} (mean 1.3 {+-} 0.3 ng/ml) or IL-1{beta} (mean 2.3 {+-} 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro{alpha}: neutrophils (PMNs) (10{sup 7} cells/ml/24 h) produced 3.7 {+-} 0.7 ng/ml. RA SF mononuclear cells produced gro{alpha}, particularly upon incubation with LPS or PHA. Immunoreactive ST gro{alpha} was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro{alpha} for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro{alpha} plays an important role in the ingress of PMNs into the RA joint. 54 refs., 6 figs., 1 tab.

  16. A protocol for the culture and isolation of murine synovial fibroblasts

    PubMed Central

    Zhao, Jinjun; Ouyang, Qingqing; Hu, Ziyou; Huang, Qin; Wu, Jing; Wang, Ran; Yang, Min

    2016-01-01

    The culture of synovial fibroblasts (SFs) is one of the most effective tools for investigating the pathology and physiology of synovial tissues and should prove useful for identifying the importance of SFs in disease as well as for the development of novel therapeutic approaches for several chronic joint diseases, such as rheumatoid arthritis. However, thus far, a detailed protocol for the primary culture and isolation of murine SFs has not been established. Therefore, the present study describes an easy and convenient method for isolating and culturing SFs from C57BL/6 mice. This protocol can be divided into 4 stages: Isolation of synovial tissues, isolation of SFs, seeding of SFs for growth in culture and purity analysis of SFs using the four cell markers, vimentin, cluster of differentiation 90.2 (CD90.2; Thy-1.2), intracellular adhesion molecule 1 (CD54) and vascular cell adhesion molecule 1 (CD106). This method is efficient and a purified population of SFs can be obtained 10 days after the initiation of culture. PMID:27446536

  17. Angiogenic and Inflammatory Properties of Psoriatic Arthritis

    PubMed Central

    Yamamoto, Toshiyuki

    2013-01-01

    Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis and included in seronegative spondyloarthropathy. PsA has several unique characteristics different from rheumatoid arthritis (RA), such as enthesopathy, dactylitis, and abnormal bone remodeling. As compared with synovitis of RA (pannus), proliferation of PsA synovium is mild and characterized by hypervascularity and increased infiltration of polymorphonuclear leukocytes in the synovial tissues. Angiogenesis plays a crucial role in cutaneous psoriasis, and several angiogenic factors such as vascular endothelial growth factor, interleukin-8, angiopoietin, tumor necrosis factor-α and transforming growth factor-β, are suggested to play an important role also in the pathophysiology of PsA. Further, IL-17 has various functions such as upregulation of proinflammatory cytokines, attraction of neutrophils, stimulation of keratinocytes, endothelial cell migration, and osteoclast formation via RANKL from activated synovial fibroblasts. Thus, IL-17 may be important in angiogenesis, fibrogenesis, and osteoclastogenesis in PsA. In this paper, roles of angiogenesis in the psoriatic synovium are discussed, which may strengthen the understanding of the pathogenesis of PsA. PMID:23819059

  18. Grammatical Arthritis.

    ERIC Educational Resources Information Center

    Bush, Don

    1994-01-01

    Discusses grammatical arthritis (an internal buildup of rules that hinders writing flexibility); four new "rules" (concerning "data is,""none are,""hopefully," and the restrictive "which"); attitudes toward English grammar; how to be a helpful editor; and where to learn about grammar. (SR)

  19. Prognostic Factors of Septic Arthritis of Hip in Infants and Neonates: Minimum 5-Year Follow-up

    PubMed Central

    Lee, Soon Chul; Seo, Sung Wook; Lee, Sung San

    2015-01-01

    Background The authors conducted the present study to identify clinical and radiological prognostic factors in infants and neonates with septic arthritis of the hip. Methods The authors retrospectively reviewed the records of 31 patients with septic arthritis of the hip. All of the patients were younger than 18 months old. Follow-up periods ranged from 5 to 17 years. The following potential variables for predicting the prognosis were included in the assessment: gender, age, underlying diseases, duration of symptoms, changes of hip joint in X-ray, concomitant osteomyelitis, elevation of erythrocyte sedimentation rate and C-reactive protein, sepsis, pus drainage, synovial fluid culture, and infecting organisms. Clinical and radiological prognoses were analyzed at the final follow-up. Results Univariate analysis demonstrated that radiological prognoses were poorer in patients who had underlying diseases, a longer duration of symptoms, and pus drainage. However, on multivariate analysis, only the variable-duration of symptoms-was found to be statistically related with a poor radiological prognosis. Conclusions Although poor prognosis for patients with several underlying diseases and radiological changes has already been established, a favorable outcome might be expected with prompt surgical drainage and appropriate antibiotics. PMID:25729527

  20. Methicillin-resistant Staphylococcus aureus enterocolitis sequentially complicated with septic arthritis: a case report and review of the literature

    PubMed Central

    2014-01-01

    Background Although most reports describing patients infected with methicillin-resistant Staphylococcus aureus enterocolitis have been published in Japan, this concept remains a matter of debate and diagnostic criteria have not yet been defined. Case presentation The general status of a 74-year-old Japanese man referred to our hospital (day 1) with severe community-acquired pneumococcal pneumonia gradually improved with antibiotic therapy. Thereafter, up to 4 L/day of acute watery diarrhea that started on day 19 was refractory to metronidazole but responded immediately to oral vancomycin. Gram staining stool samples was positive for abundant fecal leukocytes from which dominant methicillin-resistant Staphylococcus aureus (104 CFU/mL) were isolated, suggesting methicillin-resistant Staphylococcus aureus enterocolitis. High fever with methicillin-resistant Staphylococcus aureus bacteremia was evident at day 30, and suppurative right hip arthritis developed around day 71. All methicillin-resistant Staphylococcus aureus strains isolated from stools, blood and aspirated synovial fluid separated in the same manner on pulsed-field gel electrophoresis, as well as two other strains isolated from sputum, belonged to the same clone as sequence type (ST) 764 (complex clonal 5), and carried SCCmec type II. Conclusion The clinical, microbiological and molecular biological findings of this patient indicated methicillin-resistant Staphylococcus aureus enterocolitis that led to septic methicillin-resistant Staphylococcus aureus arthritis. PMID:24405901

  1. Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety

    PubMed Central

    Yang, Xiuli; Izadi, Hooman; Coleman, Adam S.; Wang, Penghua; Ma, Yongsheng; Fikrig, Erol; Anguita, Juan; Pal, Utpal

    2008-01-01

    Borrelia burgdorferi invasion of mammalian joints results in genesis of Lyme arthritis. Other than spirochete lipids, existence of protein antigens, which are abundant in joints and participate in B. burgdorferi-induced host inflammatory response, is unknown. Here, we report that major products of the B. burgdorferi basic membrane protein (bmp) A/B operon that are induced in murine and human joints, possess inflammatory properties. Compared to the wild type B. burgdorferi, an isogenic bmpA/B mutant induced significantly lower levels of pro-inflammatory cytokines TNF-α and IL-1β in cultured human synovial cells, which could be restored using bmpA/B-complemented mutants, and more directly, upon addition of recombinant BmpA, but not BmpB or control spirochete proteins. Non-lipidated and lipidated versions of BmpA induced similar levels of cytokines, and remained unaffected by treatment with lipopolysaccharide inhibitor, polymyxin B. The bmpA/B mutant was also impaired in the induction of NF-κB and p38 MAP kinase signaling pathways in synovial cells, which were activated by non-lipidated BmpA. These results show that a protein moiety of BmpA can induce cytokine responses in synovial cells via activation of the NF-κB and p38 MAP kinase pathways and thus, could potentially contribute to the genesis of Lyme arthritis. PMID:18725314

  2. Arthritis of the Wrist

    MedlinePlus

    ... is caused by just two types: osteoarthritis and rheumatoid arthritis. Osteoarthritis Osteoarthritis (OA) is a progressive condition that ... other, it results in pain, stiffness, and weakness. Rheumatoid Arthritis Rheumatoid arthritis (RA) is a chronic disease that ...

  3. What Is Rheumatoid Arthritis?

    MedlinePlus

    ... Information Arthritis Find a Clinical Trial Journal Articles Rheumatoid Arthritis PDF Version Size: 57 KB Audio Version Time: ... Size: 9.7 MB November 2014 What Is Rheumatoid Arthritis? Fast Facts: An Easy-to-Read Series of ...

  4. Arthritis and Rheumatic Diseases

    MedlinePlus

    ... Bursitis and Tendinitis, Q&A Fibromyalgia, Q&A Gout, Q&A Juvenile Arthritis, Q&A Childhood Arthritis ( ... Many people also experience fatigue and sleep disturbances. Gout. A type of arthritis resulting from deposits of ...

  5. Forms of Arthritis

    MedlinePlus

    ... stiffness, inflammation, swelling and, sometimes, destruction of joints. Gout — a form of arthritis that occurs when uric ... the joints. Some 2.1 million Americans have gout. Lupus — a form of arthritis, like rheumatoid arthritis, ...

  6. Synovial chondromatosis caused mechanical snapping elbow: a case report.

    PubMed

    Karaman, Ibrahim; Guney, Ahmet; Dogar, Fatih; Oner, Mithat; Bılal, Okkes

    2015-01-01

    Synovial chondromatosis is a rare and benign proliferative disorder of the synovial membrane in joints and bursae. Herein, we present the case of a 34-year-old male with synovial chondromatosis that caused limitation in the elbow joint in terms of mechanical function. PMID:26185473

  7. Synovial chondromatosis caused mechanical snapping elbow: a case report

    PubMed Central

    Karaman, Ibrahim; Guney, Ahmet; Dogar, Fatih; Oner, Mithat; Bılal, Okkes

    2015-01-01

    Synovial chondromatosis is a rare and benign proliferative disorder of the synovial membrane in joints and bursae. Herein, we present the case of a 34-year-old male with synovial chondromatosis that caused limitation in the elbow joint in terms of mechanical function. PMID:26185473

  8. Primary Synovial Sarcoma of Lung: A Rare Tumor

    PubMed Central

    Kumar, Parveen; Sarin, Yogesh Kumar

    2016-01-01

    Synovial sarcoma of lung is a rare tumor with few case reports in literature. Though named synovial sarcoma due to its resemblance to synovium on light microscopy, it arises from mesenchymal tissue. Here, we present a case of synovial sarcoma of lung in a 7-year old boy, with main emphasis on difficulty faced in the management. PMID:27170917

  9. Primary Synovial Sarcoma of Lung: A Rare Tumor.

    PubMed

    Raj, Prince; Kumar, Parveen; Sarin, Yogesh Kumar

    2016-01-01

    Synovial sarcoma of lung is a rare tumor with few case reports in literature. Though named synovial sarcoma due to its resemblance to synovium on light microscopy, it arises from mesenchymal tissue. Here, we present a case of synovial sarcoma of lung in a 7-year old boy, with main emphasis on difficulty faced in the management. PMID:27170917

  10. Relationship between angiogenesis and inflammation in experimental arthritis.

    PubMed

    Clavel, Gaelle; Valvason, Chiara; Yamaoka, Kunio; Lemeiter, Delphine; Laroche, Liliane; Boissier, Marie-Christophe; Bessis, Natacha

    2006-09-01

    Background. Angiogenesis is involved in rheumatoid arthritis (RA) leading to leucocyte recruitment and inflammation in the synovium. Furthermore, synovial inflammation itself further potentiates endothelial proliferation and angiogenesis. In this study, we aimed at evaluating the reciprocical relationship between synovial inflammation and angiogenesis in a RA model, namely collagen-induced arthritis (CIA). Methods. CIA was induced by immunization of DBA/1 mice with collagen type II in adjuvant. Endothelial cells were detected using a GSL-1 lectin-specific immunohistochemical staining on knee joint sections. Angiogenesis, clinical scores and histological signs of arthritis were evaluated from the induction of CIA until the end of the experiment. Angiogenesis was quantified by counting both the isolated endothelial cells and vessels stained on each section. To evaluate the effect of increased angiogenesis on CIA, VEGF gene transfer was performed using an adeno-associated virus encoding VEGF (AAV-VEGF), by intra-muscular or intra-articular injection in mice with CIA. Results. We showed an increase in synovial angiogenesis from day 6 to day 55 after CIA induction, and, moreover, joint vascularization and clinical scores of arthritis were correlated (p < 0.0001, r = 0.61). Vascularization and histological scores were also correlated (p = 0.0006, r = 0.51). Systemic VEGF overexpression in mice with CIA was followed by an aggravation of arthritis as compared to AAV-lacZ control group (p < 0.0001). In contrast, there was no difference in clinical scores between control mice and mice injected within the knee with AAV-VEGF, even if joint vascularization was higher in this group than in all other groups (p = 0,05 versus non-injected group). Intra-articular AAV-VEGF injections induced more severe signs of histological inflammation and bone destruction than AAV-Lac Z or no injection. Conclusion. Angiogenesis and joint inflammation evolve in parallel during collagen

  11. Reactive Arthritis Diagnosis

    MedlinePlus

    ... Of Spondylitis The Heart In Spondyloarthritis Inflammatory vs. Mechanical Back ... Arthritis Symptoms Because there is no specific laboratory test for reactive arthritis, doctors sometimes find it difficult ...

  12. Primary pulmonary monophasic synovial sarcoma: Evading diagnosis.

    PubMed

    Taylor, Marcus; Srinivasan, Lakshmi; Abid, Qamar

    2016-02-01

    Primary pulmonary synovial sarcoma is a very rare tumor, thus there is no consensus as to the most appropriate management. A 78-year-old man presented with nonspecific symptoms of weight loss and shortness of breath. Imaging confirmed a large right-sided mass and accompanying pleural effusion. Strong 18F-fluorodeoxyglucose uptake was found on positron-emission tomography. The preoperative work-up and intraoperative frozen section were inconclusive. Immunohistochemistry and molecular analysis confirmed the diagnosis of primary pulmonary monophasic synovial sarcoma. PMID:26612959

  13. Synovial Lipomatosis of the Glenohumeral Joint

    PubMed Central

    Safran, Ori

    2016-01-01

    Synovial lipomatosis (also known as lipoma arborescens) is a rare and benign lesion affecting synovium-lined cavities. It is characterized by hyperplasia of mature fat tissue in the subsynovial layer. Although the most commonly affected site is the knee joint, rarely additional locations such as tendon sheath and other joints are involved. We present a case of synovial lipomatosis of the glenohumeral joint in a 44-year-old man. The clinical data radiological studies and histopathologic results are described, as well as a review of the current literature. PMID:27563476

  14. Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis

    PubMed Central

    Xu, Lingxiao; Peng, Qiuyue; Xuan, Wenhua; Feng, Xiaoke; Zhang, Miaojia; Tan, Wenfeng; Xue, Meilang

    2016-01-01

    We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA. PMID:27433031

  15. Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.

    PubMed

    Xu, Lingxiao; Peng, Qiuyue; Xuan, Wenhua; Feng, Xiaoke; Kong, Xiangqing; Zhang, Miaojia; Tan, Wenfeng; Xue, Meilang; Wang, Fang

    2016-01-01

    We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA. PMID:27433031

  16. Midfoot arthritis.

    PubMed

    Patel, Amar; Rao, Smita; Nawoczenski, Deborah; Flemister, Adolf S; DiGiovanni, Benedict; Baumhauer, Judith F

    2010-07-01

    Midfoot arthritis is a common cause of significant pain and disability. Although the medial tarsometatarsal (TMT) joints provide < 7 degrees of sagittal plane motion, the more mobile lateral fourth and fifth TMT joints provide balance and accommodation on uneven ground. These small constrained TMT joints also provide stability and translate the forward propulsion motion of the hindfoot and ankle joint to the forefoot metatarsophalangeal joints from heel rise to toe-off. Posttraumatic degeneration is the primary cause of midfoot arthritis, although primary degeneration and inflammatory conditions can also affect this area. The result is a painful midfoot that can no longer effectively transmit load from the hindfoot to the forefoot. Shoe modifications and orthotic inserts are the mainstay of nonsurgical management. Successful management of midfoot arthritis with orthoses is predicated on achieving adequate joint stabilization while still allowing function. Surgical intervention typically involves arthrodesis of the medial midfoot, although the best treatment of the more mobile lateral column is a subject of debate. PMID:20595134

  17. A neglected case of giant synovial chondromatosis in knee joint.

    PubMed

    Serbest, Sancar; Tiftikçi, Ugur; Karaaslan, Fatih; Tosun, Haci Bayram; Sevinç, Hüseyin Fatih; Balci, Mahi

    2015-01-01

    Synovial chondromatosis is a rare benign condition arising from the synovial membrane of the joints, synovial sheaths or bursae around the joints. Primary synovial chondromatosis typically affects the large joints in the third to fifth decade of life. The purpose of this case report is to document this rare synovial pathology, which required open synovectomy and debridement to eradicate it. In our case, the biggest sized SOC was 20x19x6 cm, although there were many joint mice. Our case had the biggest SOC ever extracted, which to the best of my knowledge has not been reported earlier. PMID:26600905

  18. A neglected case of giant synovial chondromatosis in knee joint

    PubMed Central

    Serbest, Sancar; Tiftikçi, Ugur; Karaaslan, Fatih; Tosun, Haci Bayram; Sevinç, Hüseyin Fatih; Balci, Mahi

    2015-01-01

    Synovial chondromatosis is a rare benign condition arising from the synovial membrane of the joints, synovial sheaths or bursae around the joints. Primary synovial chondromatosis typically affects the large joints in the third to fifth decade of life. The purpose of this case report is to document this rare synovial pathology, which required open synovectomy and debridement to eradicate it. In our case, the biggest sized SOC was 20x19x6 cm, although there were many joint mice. Our case had the biggest SOC ever extracted, which to the best of my knowledge has not been reported earlier. PMID:26600905

  19. Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway.

    PubMed

    Yu, Yinhang; Li, Siming; Liu, Yaonan; Tian, Guiyou; Yuan, Qingyan; Bai, Fuliang; Wang, Wenfei; Zhang, Zhiyi; Ren, Guiping; Zhang, Yu; Li, Deshan

    2015-03-01

    It has been demonstrated that circulating FGF21 levels are elevated in the serum and synovial fluid of patients with rheumatoid arthritis (RA). The aim of this study is to investigate efficacy of FGF21 for treatment of RA and the molecular mechanisms of the therapeutic effect on collagen-induced arthritis (CIA). Mice with CIA were subcutaneously administered with FGF21 (5, 2 or 1mg·kg(-1)·d(-1)), IL-1β antibody (5mg·kg(-1)·d(-1)), IL-17A antibody (5mg·kg(-1)·d(-1)) and dexamethasone (DEX) (1mg·kg(-1)·d(-1)), respectively. The effects of treatment were determined by arthritis severity score, histological damage and cytokine production. The activation of NF-κB was analyzed by Western blotting. We also detected the levels of oxidative stress parameters. Our results showed that FGF21 had beneficial effects on clinical symptom and histological lesion of CIA mice. Similar to antibody and DEX, FGF21 treatment alleviated the severity of arthritis by reducing humoral and cellular immune responses and down-regulating the expression of pro-inflammatory cytokines. FGF21 treatment also reduced the expression of TNF-α, IL-1β, IL-6, IFN-γ and MMP-3 and increased level of IL-10 in the spleen tissue or the plasma of CIA mice in a dose-dependent manner. Furthermore, FGF21 inhibited IκBα degradation and NF-κB p65 nuclear translocation and induced significant changes of oxidative stress parameters (MDA, SOD, CAT, GSH-PX and GSH) in the plasma. FGF21 exerts therapeutic efficacy for RA through antioxidant reaction and inhibiting NF-κB inflammatory pathway. This study provides evidence that FGF21 may be a promising therapeutic agent for RA patients. PMID:25601498

  20. Photoacoustic and ultrasound dual-modality imaging for inflammatory arthritis

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  1. Cytokines in Mycoplasma hyorhinis-Induced Arthritis in Pigs Bred Selectively for High and Low Immune Responses

    PubMed Central

    Jayagopala Reddy, N. R.; Wilkie, Bruce N.; Borgs, Peter; Mallard, Bonnie A.

    2000-01-01

    Yorkshire pigs were bred selectively for high and low immune responses (H and L pigs, respectively) based on multiple antibody (Ab) and cell-mediated immune response traits. In a previous experiment, generation 4 (G4) pigs of each line were infected with Mycoplasma hyorhinis. High responders had a more rapid and higher Ab response and less polyserositis, but arthritis was more severe in H pigs than in L pigs. To test the hypothesis that line differences were attributable to differential expression of cytokines, M. hyorhinis infection was induced in pigs of G8. Arthritis was more severe clinically (P, ≤0.05) and postmortem (P, ≤0.001) when M. hyorhinis CFU were more numerous in synovial fluid (SF) of H pigs than of L pigs (P, ≤0.03). In H pigs but not L pigs, CFU and lesion scores were correlated positively. In H pigs, infection increased the frequency of expression of mRNAs for interleukin-8 (IL-8), IL-10, and tumor necrosis factor alpha (TNF-α) in mononuclear cells from synovial membranes (SM). In L pigs, IL-1α, IL-6, IL-10, and TNF-α mRNAs were increased in frequency of expression. The quantity of the cytokine message for IL-6 was increased in infected H pigs. For L pigs, infection increased the cytokine message for IL-1α, IL-6, IL-10, and TNF-α. IL-6 in SM and gamma interferon (IFN-γ) in SF were produced at a higher copy number in H pigs than in L pigs after infection. For H pigs, there were no positive rank correlations between lesion or CFU scores and cytokines. For L pigs, IL-1α, IL-8, IL-10, and TNF-α in SM correlated with CFU, while IL-6, TNF-β, and IFN-γ in SF correlated with CFU. Lesion score in L pigs correlated with IL-1α in SF. While these results indicate that H and L pigs differ in the cytokine response to M. hyorhinis infection, they do not confirm a characteristic cytokine response in association with the relative susceptibility to infection and arthritis observed in H pigs. PMID:10678919

  2. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model.

    PubMed

    Mak, J; Jablonski, C L; Leonard, C A; Dunn, J F; Raharjo, E; Matyas, J R; Biernaskie, J; Krawetz, R J

    2016-01-01

    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ "super-healer" strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not. PMID:26983696

  3. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model

    PubMed Central

    Mak, J.; Jablonski, C. L.; Leonard, C. A.; Dunn, J. F.; Raharjo, E.; Matyas, J. R.; Biernaskie, J.; Krawetz, R. J.

    2016-01-01

    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such