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Sample records for arthritis synovial fluid

  1. Synovial fluid lactic acid levels in septic arthritis.

    PubMed

    Riley, T V

    1981-01-01

    Synovial fluid lactic acid estimations were carried out on 50 samples by gas liquid chromatography. Specimens from 4 patients with bacteria arthritis, other than gonococcal, had a mean lactic acid concentration of 215 mg/dl. One patient with gonococcal arthritis had a synovial fluid lactic acid of 30 mg/dl. Forty-one patients with inflammatory arthritis and 4 patients with degenerative arthritis had mean synovial fluid lactic acid levels of 27 and 23 mg/dl respectively. The estimation of synovial fluid lactic acid is reliable in differentiating septic arthritis from inflammatory and degenerative arthritis except when the infecting organism is NEisseria gonorrhoeae.

  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.

  3. 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.

  4. Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients

    PubMed Central

    2014-01-01

    Background Rheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis. Results We have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ≥3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis. Conclusions We report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis. Sartaj Ahmad and Raja Sekhar Nirujogi

  5. 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.

  6. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis

    PubMed Central

    2010-01-01

    Introduction MicroRNAs (miRNAs), endogenous small noncoding RNAs regulating the activities of target mRNAs and cellular processes, are present in human plasma in a stable form. In this study, we investigated whether miRNAs are also stably present in synovial fluids and whether plasma and synovial fluid miRNAs could be biomarkers of rheumatoid arthritis (RA) and osteoarthritis (OA). Methods We measured concentrations of miR-16, miR-132, miR-146a, miR-155 and miR-223 in synovial fluid from patients with RA and OA, and those in plasma from RA, OA and healthy controls (HCs) by quantitative reverse transcription-polymerase chain reaction. Furthermore, miRNAs in the conditioned medium of synovial tissues, monolayer fibroblast-like synoviocytes, and mononuclear cells were examined. Correlations between miRNAs and biomarkers or disease activities of RA were statistically examined. Results Synovial fluid miRNAs were present and as stable as plasma miRNAs for storage at -20°C and freeze-thawing from -20°C to 4°C. In RA and OA, synovial fluid concentrations of miR-16, miR-132, miR-146a, and miR-223 were significantly lower than their plasma concentrations, and there were no correlation between plasma and synovial fluid miRNAs. Interestingly, synovial tissues, fibroblast-like synoviocytes, and mononuclear cells secreted miRNAs in distinct patterns. The expression patterns of miRNAs in synovial fluid of OA were similar to miRNAs secreted by synovial tissues. Synovial fluid miRNAs of RA were likely to originate from synovial tissues and infiltrating cells. Plasma miR-132 of HC was significantly higher than that of RA or OA with high diagnosability. Synovial fluid concentrations of miR-16, miR-146a miR-155 and miR-223 of RA were significantly higher than those of OA. Plasma miRNAs or ratio of synovial fluid miRNAs to plasma miRNAs, including miR-16 and miR-146a, significantly correlated with tender joint counts and 28-joint Disease Activity Score. Conclusions Plasma miRNAs had

  7. [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.

  8. Rheological properties of synovial fluids.

    PubMed

    Fam, H; Bryant, J T; Kontopoulou, M

    2007-01-01

    Synovial fluid is the joint lubricant and shock absorber [Semin. Arthritis Rheum. 32 (2002), 10-37] as well as the source of nutrition for articular cartilage. The purpose of the present paper is to provide a comprehensive review of the rheological properties of synovial fluid as they relate to its chemical composition. Given its importance in the rheology of synovial fluid, an overview of the structure and rheology of HA (hyaluronic acid) is presented first. The rheology of synovial fluids is discussed in detail, with a focus on the possible diagnosis of joint pathology based on the observed differences in rheological parameters and trends. The deterioration of viscoelastic properties of synovial fluid in pathological states due to effects of HA concentration and molecular weight is further described. Recent findings pertaining to the composition and rheology of periprosthetic fluid, the fluid that bathes prosthetic joints in vivo are reported.

  9. 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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2014-11-26

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

  12. RANTES and Chemotactic Activity in Synovial Fluids From Patients With Rheumatoid Arthritis and Osteoarthritis

    PubMed Central

    Stanczyk, Joanna; Kowalski, Marek L.; Grzegorczyk, Janina; Szkudlinska, Barbara; Jarzebska, Marzanna; Marciniak, Marek; Synder, Marek

    2005-01-01

    A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62 ± 12 and 24 ± 6 cells/HPF, resp) as compared to patients with OA (23 ± 6; P < .05 and 6 ± 2 cells/HPF; P < 0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145 ± 36 pg/mL), while OA SF was characterised by only trace amount of this chemokine (2 ± 1 pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA+MoCA; R = 0.61; P < .05). Surprisingly, RANTES correlated also positively with neutrophiles number (R = 0.77; P < 0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and composition

  13. Diagnostic value of synovial fluid anti-cyclic citrullinated peptide antibody for rheumatoid arthritis.

    PubMed

    Heidari, Behzad; Abedi, Hassan; Firouzjahi, Alireza; Heidari, Parnaz

    2010-09-01

    Early and accurate diagnosis and treatment of rheumatoid arthritis (RA) improves disease outcome. Anti-cyclic citrullinated peptide antibody (anti-CCP) which is highly specific for RA is produced locally from inflamed synovium. The present study was designed to assess the diagnostic performance of synovial fluid anti-CCP (sf-CCP) for RA. A total of 128 patients consisted of 37 RA confirmed by the American College of Rheumatology revised criteria, 91 non-RA (50 non-RA inflammatory arthritis and 41 osteoarthritis) entered the study. Serum anti-CCP (sm-CCP) and Sf-CCP were measured by the ELISA method. Receiver operating characteristics curves were constructed to determine the optimal cutoff point levels for sf-CCP and sm-CCP to discriminate RA from non-RA. Diagnostic characteristics of both variables were determined by comparison of RA patients with non-RA controls. Mean levels of sf-CCP and sm-CCP were significantly higher in RA than in non-RA (P < 0.001). Sf-CCP discriminated RA from non-RA at the optimal cutoff value of 10 U/mL with high accuracy at AUC value of 0.897 +/- 0.039, P < 0.001) sensitivity of 83.7% and specificity of 95.6%. Sm-CCP diagnosed RA at optimal cutoff level of 14.6 U/mL with respective sensitivity, specificity and AUC values of 84.8, 94.3% and 0.895 +/- 0.049, P < 0.001). Sm-CCP was strongly correlated with sf-CCP (r = 0.75, r (2) = 0.57, P < 0.0001). Two of 5 sm-CCP negative RA and 25.7% of serum rheumatoid factors negative RA were sf-CCP positive. These findings indicate that sf-CCP yields diagnostic ability as comparable as sm-CCP for RA. Respecting to local production of sf-CCP prior to disease onset, therefore sf-CCP determination may offer earlier as well as additional diagnostic information which may be more helpful in recognizing RA particularly among recent onset arthritis.

  14. Synovial effusion and synovial fluid biomarkers in psoriatic arthritis to assess intraarticular tumor necrosis factor-α blockade in the knee joint

    PubMed Central

    2010-01-01

    Introduction The purpose of this study was theevaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA). Methods Systemic and local disease activity indexes (disease activity score (DAS); the Ritchie articular index (mRAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular (THOMP) and joint articular (KJAI)-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml to 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a 10-week period. Total SF white blood cell (WBC) counts (WBC/μl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8 out of 14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105. Results At baseline, CRP and/or ESR were significantly correlated with SF-CK (interleukin- (IL-)1β, IL-1Ra, IL-6, IL-8) and CCK (CCL3). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/μl and in SF-CK (IL-1β, IL-1Ra, IL-6 and IL-22). Pre- and post-IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1β with CD45; IL-1β and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3). Conclusions Synovial effusion regression is a reliable indicator

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

    PubMed

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

    2015-09-01

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

  16. D-penicillamine and D-penicillamine-protein disulphide in plasma and synovial fluid of patients with rheumatoid arthritis.

    PubMed

    Joyce, D A; Day, R O

    1990-10-01

    1. The plasma pharmacokinetics of D-penicillamine (D-pen) and D-penicillamine-albumin disulphide (D-pen-alb) were examined over a dosage interval in six patients with rheumatoid arthritis. In two of these, 24 h synovial fluid profiles of D-pen and D-pen-alb were also obtained. 2. D-pen was undetectable in plasma at the beginning of the study. The peak concentration (5.4 +/- 1.2 microM) occurred at between 45 min and 2 h and the mean elimination half-life was 0.6 h. D-pen-alb, however, was present at a mean plasma concentration of 19.1 microM prior to dosage, peaked at 26.2 microM and was eliminated with a half-life of 40 h. 3. D-pen concentrations in synovial fluid rose more slowly and peaked lower than in plasma. D-pen-alb was present in synovial fluid of the patients at 50.1% and 83.6%, respectively, of the simultaneous plasma concentration prior to dosage. Concentrations varied during the study interval, corresponding to changes in plasma concentrations. 4. These results demonstrate that D-pen forms stable conjugates with protein in treated patients. The presence of D-pen-alb in relatively high concentrations throughout the dosage interval contrasts with the low concentrations and rapid elimination of D-pen. Both D-pen and D-pen-alb were also shown to be present at the putative site of drug action (the inflamed synovial joint) in concentrations lower than those in plasma.

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

    PubMed

    Yagupsky, P; Press, J

    1997-09-01

    Synovial fluid specimens obtained from patients with arthritis were plated onto solid media (conventional cultures) or inoculated into an Isolator 1.5 microbial tube (Isolator cultures), and the yield and time to detection of organisms were compared. Overall, 144 specimens obtained from 137 patients were processed, and 31 (21.5%) cultures obtained from 29 patients were positive by at least one method. Staphylococcus aureus was isolated from 12 patients, Streptococcus pneumoniae and Kingella kingae were isolated from 4 patients each, group G streptococci were isolated from 3 patients, Staphylococcus epidermidis and members of the family Enterobacteriaceae were isolated from 2 patients each, and Streptococcus mitis and Peptostreptococcus prevotii were isolated from 1 patient each. Overall, the causative organism was detected in 31 of 31 (100.0%) Isolator cultures and 24 of 31 (77.4%) conventional cultures (P < 0.02). Twenty-nine of 31 (93.5%) positive Isolator cultures and 20 of 24 (83.3%) conventional cultures were positive by the second day of incubation. Among the 24 cultures positive by both methods, higher numbers of CFU per milliliter were detected with the Isolator system in 13 cultures and with conventional cultures in 2 cultures (P < 0.002). Inoculation of synovial fluid into an Isolator 1.5 microbial tube improves the recovery of organisms causing septic arthritis.

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

    PubMed

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

    2017-01-06

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

  19. Effects of an oral administration of glucosamine-chondroitin-quercetin glucoside on the synovial fluid properties in patients with osteoarthritis and rheumatoid arthritis.

    PubMed

    Matsuno, Hiroaki; Nakamura, Hiroshi; Katayama, Kou; Hayashi, Seigaku; Kano, Syogo; Yudoh, Kazuo; Kiso, Yoshinobu

    2009-02-01

    The effects of an orally administered combination of a glucosamine-chondroitin-quercetin glucoside (GCQG) supplement on the synovial fluid properties of patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were investigated from the clinical nutrition view point. In this study, forty-six OA and twenty-two RA patients were administered with the GCQG supplement orally for 3 months. Several parameters of the knee joints were monitored before and after supplementation. The OA patients showed a significant improvement in pain symptoms, daily activities (walking and climbing up and down stairs), and visual analogue scale, and changes in the synovial fluid properties with respect to the protein concentration, molecular size of hyaluronic acid, and chondroitin 6-sulphate concentration were also observed. However, no such effects were observed in the RA patients. These results suggest that the GCQG supplement exerted a special effect on improving the synovial fluid properties in OA patients.

  20. Ruptured bilateral synovial cysts in presumed gonococcal arthritis.

    PubMed

    Terho, P; Viikari, J; Mäkelä, P; Toivanen, A

    1977-01-01

    A man with gonococcal urethritis who developed septic arthritis of both knees is described. The arthritis was complicated by rupture of bilateral synovial cysts. A rise in serum gonococcal complement-fixation antibody titer was demonstrated. Complement-fixing gonococcal antibodies with a high titer were observed in this synovial fluid. The patient responded well to antibiotic treatment and there was no permanent damage to his knee joints.

  1. Synovial fluid antigen-presenting cells unmask peripheral blood T cell responses to bacterial antigens in inflammatory arthritis.

    PubMed Central

    Life, P F; Viner, N J; Bacon, P A; Gaston, J S

    1990-01-01

    We and others have previously shown that synovial fluid (SF) mononuclear cells (MC) from patients with both reactive arthritis and other inflammatory arthritides proliferate in vitro in response to bacteria clinically associated with the triggering of reactive arthritis. In all cases, such SFMC responses are greater than the corresponding peripheral blood (PB) MC responses, often markedly so, and the mechanism for this is unclear. We have investigated this phenomenon by comparing the relative abilities of irradiated non-T cells derived from PB and SF to support autologous T cell responses to ReA-associated bacteria. Seven patients whose SFMC had been shown previously to respond to bacteria were studied. We demonstrate antigen-specific responses of PB T cells to bacteria in the presence of SF non-T cells which are in marked contrast to the minimal responses of either unfractionated PBMC or PB T cells reconstituted with PB non-T cells. We also show that PB, but not SF T cells respond strongly to autologous SF non-T cells in the absence of antigen or mitogen. These findings demonstrate that SF antigen-presenting cells (APC) are potent activators of PB T cells. We conclude that the contrasting responses of SFMC and PBMC to bacterial antigens may be accounted for at least in part by an enhanced ability of SF APC to support T cell proliferative responses. PMID:2311298

  2. Expression of TIM-3 on CD4+ and CD8+ T cells in the peripheral blood and synovial fluid of rheumatoid arthritis.

    PubMed

    Li, Shufeng; Peng, Dayong; He, Yeteng; Zhang, Hu; Sun, Huaqiang; Shan, Shiying; Song, Yuanlin; Zhang, Shuzhen; Xiao, Hong; Song, Haihan; Zhang, Ming

    2014-10-01

    Rheumatoid arthritis (RA) is characterized by a chronic inflammatory process that targets the synovial lining of diarthrodial joints. TIM-3 plays a key role in the negative regulation of the immune response. In this study, we investigated the expression of TIM-3 on CD4+ and CD8+ T cells from systemic (peripheral blood) and local (synovial fluid) perspectives of RA. Level of TIM-3+ cells from peripheral blood and synovial fluid of patients as well as peripheral blood of healthy controls was measured by flow cytometry. Results showed that TIM-3 expression was significantly increased in both CD4+ and CD8+ T cells in the peripheral blood of RA (p < 0.001 and p < 0.001, respectively). Furthermore, patients revealed even higher expression of TIM-3 in CD4+ and CD8+ T cells in synovial fluid than in peripheral blood. When comparing TIM-3 level with the severity of RA, we identified that the percentage of TIM-3 on both peripheral CD4+ and peripheral CD8+ T cells was negatively correlated with disease activity score 28 (DAS28) of the patients. Similarly, TIM-3 on synovial fluid CD4+ and CD8+ T cells also revealed inverse correlation with DAS28 of the cases. Our data demonstrate a negative correlation between TIM-3 and the disease progression of RA.

  3. 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.

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

    PubMed Central

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

    2015-01-01

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

  5. Synovial fluid analysis.

    PubMed

    Brannan, Scott R; Jerrard, David A

    2006-04-01

    AsA prompt and accurate diagnosis of a painful, swollen joint is imperative, primarily in the case of a septic joint, as delayed therapy may result in progression of disease or permanent loss of function. Procurement and analysis of synovial fluid (SF) are paramount in helping the clinician to determine a patient's clinical condition and further course of treatment. Measurement of white blood cell (WBC) counts, crystal analysis by polarized microscopy, and microbiologic studies including Gram stain and culture are the SF parameters that are collectively most important in the ultimate determination by a clinician of the presence or absence of an infectious or inflammatory joint. It is important for the clinician to understand and recognize the limitations of various SF parameters to minimize under-treating patients with potentially serious joint pathology.

  6. Suppression of Dendritic Cell Maturation and T Cell Proliferation by Synovial Fluid Myeloid Cells from Mice with Autoimmune Arthritis

    PubMed Central

    Egelston, Colt; Kurkó, Júlia; Besenyei, Timea; Tryniszewska, Beata; Rauch, Tibor A.; Glant, Tibor T.; Mikecz, Katalin

    2012-01-01

    Objective To determine whether myeloid cells (such as granulocytes) present in the synovial fluid (SF) of arthritic joints have an impact on adaptive immunity. Specifically, we investigated the effects of SF cells, harvested from the joints of mice with proteoglycan (PG)-induced arthritis (PGIA), on dendritic cell (DC) maturation and antigen-specific T-cell proliferation. Methods We monitored DC maturation (MHC class II and CD86 expression) by flow cytometry upon co-culture of DCs with SF or spleen myeloid cells from mice with PGIA. The effects of these myeloid cells on T-cell proliferation were studied using T cells purified from PG-specific T cell receptor transgenic (PG-TCR-Tg) mice. Phenotypic analysis of myeloid cells was performed employing immunostaining, RT-PCR, Western blot, and biochemical assays. Results Inflammatory SF cells significantly suppressed the maturation of DCs upon co-culture. PG-TCR-Tg T cells cultured with antigen-loaded DCs showed dramatic decreases in proliferation in the presence of SF cells. Spleen myeloid cells from arthritic mice did not have suppressive effects. SF cells were unable to suppress CD3/CD28-stimulated proliferation of the same T cells, suggesting a DC-dependent mechanism. SF cells exhibited all of the characteristics of myeloid-derived suppressor cells (MDSCs), and exerted suppression primarily through production of nitric oxide and reactive oxygen species by granulocyte-like cells. Conclusion SF in the joints of mice with PGIA contains a population of granulocytic MDSCs that potently suppress DC maturation and T-cell proliferation. These MDSCs have the potential to limit the expansion of autoreactive T cells, thus breaking the vicious cycle of autoimmunity and inflammation. PMID:22492217

  7. 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

  8. 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

  9. [Synovial membrane diagnostic assessment in rheumatoid arthritis].

    PubMed

    Ostendorf, B; Dann, P; Friemann, J; Pauly, T; Schneider, M

    2002-04-01

    Rheumatoid arthritis (RA) is the most frequent inflammatory rheumatic disease. At the beginning of the disease, where, based on today's knowledge the therapeutic possibilities are largest, the diagnostic methods do not permit a differentiated estimation of the prognosis. Conventional x-rays are mostly normal and serum markers unspecific. So far--in contrast to other diseases--only little information had been drawn from the pathomorphologic substrate "synovialis" itself to assess the prognosis. Reasons therefor were found in difficulties in obtaining synovial tissue besides surgical interventions, particularly in patients with early arthritis. By minimalizing the diagnostic instruments and improvement of the technique, synovial tissue sampling in RA has become minimally invasive and it is even possible to perform on the smallest joints, such as finger joints. Hereby, synovial analysis is open for detecting pathways of inflammation and joint destruction, which might support the advancement of new therapeutic strategies, followed by a better prognosis and outcome of RA.

  10. 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 ...

  11. Electrophoretic characterization of species of fibronectin bearing sequences from the N-terminal heparin-binding domain in synovial fluid samples from patients with osteoarthritis and rheumatoid arthritis

    PubMed Central

    Peters, John H; Carsons, Steven; Yoshida, Mika; Ko, Fred; McDougall, Skye; Loredo, Grace A; Hahn, Theodore J

    2003-01-01

    Fragments of fibronectin (FN) corresponding to the N-terminal heparin-binding domain have been observed to promote catabolic chondrocytic gene expression and chondrolysis. We therefore characterized FN species that include sequences from this domain in samples of arthritic synovial fluid using one-and two-dimensional (1D and 2D) Western blot analysis. We detected similar assortments of species, ranging from ~47 to greater than 200 kDa, in samples obtained from patients with osteoarthritis (n = 9) versus rheumatoid arthritis (n = 10). One of the predominant forms, with an apparent molecular weight of ~170 kDa, typically resolved in 2D electrophoresis into a cluster of subspecies. These exhibited reduced binding to gelatin in comparison with a more prevalent species of ~200+ kDa and were also recognized by a monoclonal antibody to the central cell-binding domain (CBD). When considered together with our previous analyses of synovial fluid FN species containing the alternatively spliced EIIIA segment, these observations indicate that the ~170-kDa species includes sequences from four FN domains that have previously, in isolation, been observed to promote catabolic responses by chondrocytes in vitro: the N-terminal heparin-binding domain, the gelatin-binding domain, the central CBD, and the EIIIA segment. The ~170-kDa N-terminal species of FN may therefore be both a participant in joint destructive processes and a biomarker with which to gauge activity of the arthritic process. PMID:14680507

  12. High levels of the proNGF peptides LIP1 and LIP2 in the serum and synovial fluid of rheumatoid arthritis patients: evidence for two new cytokines.

    PubMed

    Dicou, Eleni

    2008-02-01

    The proNGF peptides LIP1 and LIP2 display multiple biological and physiological properties several of which share common features with the nerve growth factor (NGF). The objective of this study was firstly to demonstrate the presence of these peptides in the human sera and secondly to provide evidence for their involvement in inflammatory diseases. Their levels measured by specific enzyme-linked immunosorbent assays (ELISA) were found to be more than 10-fold higher in sera of patients with rheumatoid arthritis (RA), as compared to healthy controls. High levels of LIP1 and LIP2 were also detected in the synovial fluid (SF) of RA patients. These results provide first evidence for a cytokine-like role of the LIP1 and LIP2 peptides.

  13. 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

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

    PubMed

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

    2014-07-01

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

  15. Elevated Serum and Synovial Fluid Levels of Interleukin-34 in Rheumatoid Arthritis: Possible Association with Disease Progression via Interleukin-17 Production

    PubMed Central

    Tian, Ye; Xia, Liping; Lu, Jing

    2013-01-01

    To measure the levels of interleukin-34 (IL-34) in serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and to evaluate the effect of recombination human (rh) IL-34 on IL-17 production by peripheral blood mononuclear cells (PBMC) in RA patients, the serum and SF levels of IL-34, and the production of IL-17 by rhIL-34-treated PBMC of RA patients were measured by enzyme-linked immunosorbent assay. We also tested the change of IL-34 level after tumor necrosis factor (TNF)-α blockade therapy in 30 RA patients. In contrast to almost no detectable IL-34 in osteoarthritis (OA) and healthy serum, IL-34 could be detected in 93 out of the 125 RA cases (74.4%). Sera IL-34 levels were significantly higher in RA patients compared with the controls and correlated with disease activity. IL-34 levels were higher in SF samples than in sera in 11 RA patients. The level of serum IL-34 decreased after anti-TNF treatment. In the presence of rhIL-34, stimulation of PBMC from RA patients resulted in increased production of IL-17. These findings suggest that IL-34 may play a role in the pathogenesis of RA. PMID:23421370

  16. Evaluation of a Real-Time PCR Assay for Simultaneous Detection of Kingella kingae and Staphylococcus aureus from Synovial Fluid in Suspected Septic Arthritis

    PubMed Central

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

    2014-01-01

    Direct plating of synovial fluid (SF) on agar-based media often fails to identify pathogens in septic arthritis (SA). We developed a PCR assay for the simultaneous detection of Kingella kingae and Staphylococcus aureus from SF to evaluate molecular detection in SF and to estimate the incidence of K. kingae in SA in North America. The assay was based on detection of the cpn60 gene of K. kingae and the spa gene of S. aureus in multiplex real-time PCR. K. kingae was identified in 50% of patients between 0 and 5 yr of age (n=6) but not in any patients >18 yr old (n=105). Direct plating of SF on agar-based media failed to detect K. kingae in all samples. The PCR assay was inferior to the culture-based method for S. aureus, detecting only 50% of culture-positive cases. Our findings suggest that K. kingae is a common pathogen in pediatric SA in North America, in agreement with previous reports from Europe. PCR-based assays for the detection of K. kingae may be considered in children with SA, especially in those with a high degree of clinical suspicion. PMID:24982837

  17. Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

    PubMed Central

    Poole, A R; Ionescu, M; Swan, A; Dieppe, P A

    1994-01-01

    The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases. PMID:7518830

  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.

  19. 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

  20. Expression of CD44 on rheumatoid synovial fluid lymphocytes.

    PubMed Central

    Kelleher, D; Murphy, A; Hall, N; Omary, M B; Kearns, G; Long, A; Casey, E B

    1995-01-01

    OBJECTIVES--To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS--Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS--CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS--Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules. Images PMID:7545382

  1. The detection of calcium pyrophosphate crystals in the synovial fluid of patients with rheumatoid arthritis using the cytospin technique: prevalence and clinical correlation.

    PubMed

    Theiler, Georg; Quehenberger, Franz; Rainer, Franz; Neubauer, Manfred; Stettin, Mariana; Robier, Christoph

    2014-01-01

    There are only a few studies dealing with the detection and clinical impact of calcium pyrophosphate (CPPD) crystals in patients with rheumatoid arthritis (RA) published to date. In particular, data determined by the cytospin technique, which is an effective tool to enhance the crystal detection rate, are lacking. The objectives of this study were to determine the prevalence of CPPD crystals in the synovial fluid (SF) of patients with RA and to investigate whether the detection of CPPD crystals is correlated with demographic, clinical and serological features. We examined 113 consecutive SF samples of patients with RA, obtained from therapeutic arthrocentesis of knee joints. After cytocentrifugation, the sediments were examined by polarized microscopy for the occurrence of CPPD crystals. Demographic, clinical and serological data, acquired from the medical records, were compared between crystal-positive and crystal-negative subjects. CPPD crystals were observed in 20 of the 113 cases, representing 17.7%. CPPD-positive and CPPD-negative subjects did not differ significantly in sex, duration of disease, Steinbrocker radiologic stage, disease activity score 28, as well as serum rheumatoid factor and anti-CCP positivity. Patients positively tested for CPPD crystals had a significantly higher age than CPPD-negative patients (p < 0.0001). An age-independent association of long-time treatment with diuretics and CPPD crystal formation was not found. In conclusion, demographic, clinical and serological characteristics of patients with RA were not associated with the occurrence of CPPD crystals. Age was the only significant influencing factor on CPPD crystal formation in patients with RA.

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

    PubMed

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

    2014-07-01

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

  3. Anomalies of intra-synovial citrullination: is there any interest in the diagnosis of early rheumatoid arthritis?

    PubMed

    Mrabet, Dalila; Laadhar, Lilia; Haouet, Slim; Sahli, Héla; Zouari, Béchir; Makni, Sondès; Sellami, Slaheddine

    2013-03-01

    Autoantibodies to citrullinated proteins (ACPA) are specifically associated with rheumatoid arthritis (RA) and seem to play an important role in its pathogenesis. The specific immunological conflict between ACPA and citrullinated fibrin plays a major role in the self-maintenance of synovial inflammation by forming fibrin deposits in the synovial tissue. These deposits, secondarily citrullinated by a local peptidylarginine deiminase (PADI) enzyme activity, seem to maintain the immunological conflict and the inflammation. Our objective in this work is to study the anomalies of citrullination in a group of patients with early RA, in comparison with a control group of patients suffering from undetermined inflammatory arthritis, osteoarthritis and spondyloarthropathy. For this purpose, we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of ACPA in serum and synovial fluid. By immunohistochemistry, subtype 4 of PADI was also sought in the synovial biopsies taken from all our patients. We found that the ACPA levels in serum and synovial fluid were significantly higher in patients with RA. The enzyme PADI4 was found only in the group with RA and was statistically correlated with ACPA mean levels in sera and synovial fluid. The expression of PADI4 seems to correlate with intra-synovial deposits of fibrin in RA. However, determination of synovial ACPA levels and detection of intra-synovial PADI4 deposits are of no additional benefit compared with assessment of ACPA levels in serum for the diagnosis of early RA.

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

    PubMed

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

    2002-10-01

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

  5. 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

  6. Type II collagen antibody response is enriched in the synovial fluid of rheumatoid joints and directed to the same major epitopes as in collagen induced arthritis in primates and mice

    PubMed Central

    2014-01-01

    Introduction Antibodies towards type II collagen (CII) are detected in patients with rheumatoid arthritis (RA) and in non-human primates and rodents with collagen induced arthritis (CIA). We have previously shown that antibodies specific for several CII-epitopes are pathogenic using monoclonal antibodies from arthritic mice, although the role of different anti-CII epitopes has not been investigated in detail in other species. We therefore performed an inter-species comparative study of the autoantibody response to CII in patients with RA versus monkeys and mice with CIA. Methods Analysis of the full epitope repertoire along the disease course of CIA was performed using a library of CII triple-helical peptides. The antibody responses to the major CII epitopes were analyzed in sera and synovial fluid from RA patients, and in sera from rhesus monkeys (Macaca mulatta), common marmosets (Callithrix jacchus) and mice. Results Many CII epitopes including the major C1, U1, and J1 were associated with established CIA and arginine residues played an important role in the anti-CII antibody interactions. The major epitopes were also recognized in RA patients, both in sera and even more pronounced in synovial fluid: 77% of the patients had antibodies to the U1 epitope. The anti-CII immune response was not restricted to the anti-citrulline protein antibodies (ACPA) positive RA group. Conclusion CII conformational dependent antibody responses are common in RA and are likely to originate from rheumatoid joints but did not show a correlation with ACPA response. Importantly, the fine specificity of the anti-CII response is similar with CIA in monkeys and rodents where the recognized epitopes are conserved and have a major pathogenic role. Thus, anti-CII antibodies may both contribute to, as well as be the consequence of, local joint inflammation. PMID:25005029

  7. Epstein-Barr virus (EBV). VII. Established lymphoid cell line (IVPat-88) obtained from synovial fluid of a patient with aseptic arthritis.

    PubMed

    Pătraşcu, I V; Ghenoiu, O; Tache, M; Stoicescu, M; Cajal, N

    1989-01-01

    Attempts have been made to culture mononuclear cells from synovial fluid of 8 patients with arthropathy, and have led to the development of the lymphoid cell line IVPat-88. Cell line has been propagated by serial passages for more than 14 weeks in continuous culture. The cells grew as single, free-floating individuals, or in dense clumps without adherence to glass or plastic surface. All these cells were identified as altered lymphoblasts because of their growth pattern and uniform morphology, and the presence of Epstein-Barr Viral Capsid Antigen (VCA) in 5 to 10% of the cells. The cell concentration varied during the period of culture from about 300,000 to 1,700,000 cells per ml, and mean doubling time during phases of active growth was 42 and 60 hours in MEM and RPMI 1640 tissue culture media, respectively. The methods used and the characteristics of the cell line are described.

  8. Measurement of equine myeloperoxidase (MPO) activity in synovial fluid by a modified MPO assay and evaluation of joint diseases - an initial case study.

    PubMed

    Fietz, S; Bondzio, A; Moschos, A; Hertsch, B; Einspanier, R

    2008-06-01

    The aim of this study was to develop a specific myeloperoxidase (MPO) activity assay in the synovial fluid of horses and investigate whether MPO activity is increased in different forms of joint diseases. Synovial fluid samples were taken from affected joints from horses with osteoarthritis, chronic non-septic arthritis and septic arthritis, and from healthy control horses. MPO activity was measured using a specific modified o-dianisidine-assay containing 4-aminobenzoic acid hydrazide as a potent and specific inhibitor of the MPO. This assay is characterized by high reproducibility. The results reveal only a slight elevation of MPO activity in the synovial fluid of horses with osteoarthritis and chronic non-septic arthritis. However, in the cases of septic arthritis a significant increase in MPO activity was found when compared to the controls. In conclusion the first field study suggests that synovial fluid MPO may be used as a marker for septic arthritis in horses.

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

    PubMed Central

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

    1992-01-01

    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

  10. Assessment of rheumatoid activity based on clinical features and blood and synovial fluid analysis.

    PubMed Central

    Farr, M; Kendall, M J; Young, D W; Meynell, M J; Hawkins, C F

    1976-01-01

    Joint inflammation in rheumatoid arthritis has been assessed, and the most useful guides to disease activity were determined by analysis of synovial fluid and blood together with the history of joint disability. The patient's own evaluation of the amount of pain suffered was the most useful clinical assessment. Differential cell count and glucose estimations were the most helpful guides in the synovial fluid, while C-reactive protein in the serum most accurately reflected disease activity. The effects of systemic steroids on these indices were studied, and the differences between seronegative and seropositive patients noted. PMID:942273

  11. 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.

  12. Complement C4-derived monocyte-directed chemotaxis-inhibitory factor. A molecular mechanism to cause polymorphonuclear leukocyte-predominant infiltration in rheumatoid arthritis synovial cavities.

    PubMed Central

    Matsubara, S.; Yamamoto, T.; Tsuruta, T.; Takagi, K.; Kambara, T.

    1991-01-01

    To reveal the mechanism of the lesser infiltration of monocytes in synovial cavities with rheumatoid arthritis despite the presence of chronic inflammation, the synovial fluid from 15 rheumatoid arthritis patients was analyzed with respect to leukocyte chemotaxis. The synovial fluid possessed strong chemotactic activity to polymorphonuclear leukocytes but rather suppressed one to monocytes. The synovial fluid contained two different inhibitory activities in monocyte chemotaxis. One, which also suppressed polymorphonuclear leukocyte chemotaxis, was identified as alpha 1 protease inhibitor. The other, with molecular weight of 8 kd, possessed the specificity to monocytes and shared the antigenicity with complement C4 but not with C3 or C5. A similar inhibitor was generated in normal human plasma when the classical pathway of the complement system was initiated with aggregated human IgG, while it was not when alternative pathway was initiated with zymosan. The small size factor in the synovial fluid, apparently derived from C4, seemed to be a cyto-directed factor that might block an early part of signal transduction system of monocytes in the chemotaxis. After removal of the small-size inhibitor, the synovial fluid exhibited chemotactic ability to monocytes. Therefore the apparent C4-derived factor might play a key role in the polymorphonuclear leukocyte-predominant infiltration in the synovial fluid of rheumatoid arthritis. PMID:2024711

  13. 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.

  14. Normal human synovial fluid: osmolality and exercise-induced changes.

    PubMed

    Baumgarten, M; Bloebaum, R D; Ross, S D; Campbell, P; Sarmiento, A

    1985-12-01

    We measured the osmolality of human synovial fluid in the knees of healthy young adults following minimum activity and exercise. These results were compared with each subject's blood-serum osmolality. The synovial fluid was hyperosmolal with minimum activity, decreasing to blood-serum levels after exercise.

  15. The epigenome of synovial fibroblasts: an underestimated therapeutic target in rheumatoid arthritis.

    PubMed

    Frank-Bertoncelj, Mojca; Gay, Steffen

    2014-01-01

    Perturbed epigenetic landscape and deregulated microRNA networks are central to the permanent activation and aggressiveness of synovial fibroblasts in rheumatoid arthritis. Current anti-cytokine therapies, although effectively halting synovitis, cannot reverse the stably activated destructive phenotype of rheumatoid arthritis synovial fibroblasts,offering rather limited protection against ongoing joint destruction in rheumatoid arthritis. Targeting the deregulated epigenome of rheumatoid arthritis synovial fibroblasts is key to developing joint-protective strategies in rheumatoid arthritis. To date, different pathogenic mechanisms have been identified that can profoundly impact the epigenetic derangements in rheumatoid arthritis synovial fibroblasts, including increased consumption of S-adenosylmethionine,a principal methyl donor in DNA methylation reactions, together with deregulation of crucial DNA- and histonemodifying enzymes. Re-establishing globally disturbed DNA methylation patterns in rheumatoid arthritis synovial fibroblasts by supplementing S-adenosylmethionine while preventing its leakage into polyamine cycles may bea promising therapeutic strategy in rheumatoid arthritis and the first epigenetic treatment to target rheumatoid arthritis synovial fibroblasts at the scene of the crime. Given the dynamic nature and reversibility of epigenetic modifications, their involvement in human diseases and recent perspectives on epigenetic therapies in cancer, epigenetic targeting of rheumatoid arthritis synovial fibroblasts should be within future reach.

  16. The epigenome of synovial fibroblasts: an underestimated therapeutic target in rheumatoid arthritis

    PubMed Central

    2014-01-01

    Perturbed epigenetic landscape and deregulated microRNA networks are central to the permanent activation and aggressiveness of synovial fibroblasts in rheumatoid arthritis. Current anti-cytokine therapies, although effectively halting synovitis, cannot reverse the stably activated destructive phenotype of rheumatoid arthritis synovial fibroblasts, offering rather limited protection against ongoing joint destruction in rheumatoid arthritis. Targeting the deregulated epigenome of rheumatoid arthritis synovial fibroblasts is key to developing joint-protective strategies in rheumatoid arthritis. To date, different pathogenic mechanisms have been identified that can profoundly impact the epigenetic derangements in rheumatoid arthritis synovial fibroblasts, including increased consumption of S-adenosylmethionine, a principal methyl donor in DNA methylation reactions, together with deregulation of crucial DNA- and histone-modifying enzymes. Re-establishing globally disturbed DNA methylation patterns in rheumatoid arthritis synovial fibroblasts by supplementing S-adenosylmethionine while preventing its leakage into polyamine cycles may be a promising therapeutic strategy in rheumatoid arthritis and the first epigenetic treatment to target rheumatoid arthritis synovial fibroblasts at the scene of the crime. Given the dynamic nature and reversibility of epigenetic modifications, their involvement in human diseases and recent perspectives on epigenetic therapies in cancer, epigenetic targeting of rheumatoid arthritis synovial fibroblasts should be within future reach. PMID:25165988

  17. Osmolarity regulates chondrogenic differentiation potential of synovial fluid derived mesenchymal progenitor cells.

    PubMed

    Bertram, Karri L; Krawetz, Roman J

    2012-06-08

    Cartilage is one of few tissues where adult stem/progenitor cells have not been putatively identified. Recent studies have provided strong evidence that a sub-population of mesenchymal progenitor cells (MPCs) derived from the synovial fluid may be able to affect some degree of cartilage repair both in vivo and in vitro/ex vivo, however this does not appear to be the case in patients with arthritis. Previously, it has been found that synovial fluid osmolarity is decreased in patients with osteoarthritis (OA) or Rheumatoid arthritis (RA) and these changes in osmolarity have been linked to changes in chondrocyte gene regulation. However, it is yet unknown if changes in osmolarity regulate the gene expression in synovial fluid MPCs (sfMPCs), and by extension, chondrogenesis of this cell population. In the present study we have collected synovial fluid samples from normal, OA and RA knee joints, quantified the osmolarity of the fluid and modified the culture/differentiation media to span a range of osmolarities (264-375 mOsm). Chondrogenesis was measured with Alcian blue staining of cultures in addition to quantitative PCR (qPCR) using probes to Sox9, ACAN and Col2A1. Overall, sfMPCs from arthritic joints demonstrated decreased chondrogenic potential compared to sfMPCs isolated from normal synovial fluid. Furthermore, the sfMPCs retained increased chondrogenic potential if differentiated under the same osmolarity conditions for which they were initially derived within. In conclusion, it does appear the synovial fluid osmolarity regulates the chondrogenic potential of sfMPCs, however, further study is required to elucidate the mechanism by which the changes in osmolarity are sensed by the cells and regulate chondrogenic gene expression.

  18. Determination of lead in paired samples of human blood and synovial fluid

    SciTech Connect

    Villegas-Navarro, A.; Rosales, D.; Bustos, E.; Reyes, R.; Reyes, J.L.; Dieck, T.A.; Heredia, A. )

    1992-09-01

    In spite of the numerous papers published on the toxicity of lead in mammals, little is known about its effects in synovial fluid and bone joints. Our literature search showed a lack of quantitative studies regarding the concentration of lead in human synovial fluid; in addition, normal values regarding the threshold for poisoning by lead in that fluid are unknown. The available literature published corresponds to samples of human wounds by lead bullets localized close to or in a joint. Some of those papers dealing with lead-induced arthritis include symptoms of plumbism. They clearly demonstrate the ability of synovial fluid to dissolve lead and thereby make it available for systemic absorption. The molecular mechanism whereby this process is performed is still unknown, although it would be of interest because of its possible relationship with joint pain, a common problem in patients with lead poisoning that so far has not been fully explained. In a series of experiments with cattle, we found an average ratio of lead between synovial fluid and blood for paired observations of 4.2, although we have not found similar reports, and there is not sufficient information to make a total interpretation of these data. The purpose of this study was to determine the concentration of lead in synovial fluid and blood of corpses and to establish a possible numerical relationship between those two variables. 19 refs., 1 fig., 1 tab.

  19. Terminal monosaccharide screening of synovial immunoglobulins G and A for the early detection of rheumatoid arthritis.

    PubMed

    Kratz, Ewa Maria; Borysewicz, Krzysztof; Katnik-Prastowska, Iwona

    2010-08-01

    The expressions of some terminal glycotopes of synovial immunoglobulins G, A, and M were analysed in relation to rheumatoid arthritis (RA) progression defined according to early and advanced radiological changes in patients' hands. The relative amounts of terminal monosaccharides were determined by lectin-immunoblotting of immunoglobulin preparations using appropriate lectins able to recognize alpha2,6-linked (Sambucus nigra agglutinin) and alpha2,3-linked (Maackia amurensis agglutinin) sialic acid, galactose (Ricinus communis agglutinin I), N-acetylglucosamine (Griffonia simplicifolia agglutinin II) as well as alpha1,6-linked (Aleuria aurantia lectin), alpha1,3-linked (Lotus tetragonolobus agglutinin), and alpha1,2-linked (Ulex europaeus agglutinin) fucose. The results indicate differences between early and advanced RA stages in the terminal sugar exposition of synovial IgG and IgA, but not IgM. The galactose-deficient glycotope with exposed N-acetylglucosamine of the synovial 33.1-kDa IgG fragment appeared exclusively in the early stage of RA. In contrast, this glycotope of intact synovial IgG and IgA was present in both groups, although with higher proportions in advanced RA. The proportions of the sialyl and fucosyl determinants of intact synovial A and G immunoglobulins were clearly lower in the early RA group than in the advanced. The analysis of terminal oligosaccharide exposition in IgG, IgG fragments, and IgA present in the synovial fluid of RA patients might be applicable as a stage-specific marker in the diagnosis and therapy of RA patients.

  20. Temporomandibular joint biomechanical restrictions: the fluid and synovial membrane.

    PubMed

    Cascone, P; Vetrano, S; Nicolai, G; Fabiani, F

    1999-07-01

    The authors analyze the functions of the synovial membrane and the chemical-physical properties of synovial fluid. In particular they evaluate the role played by synovial fluid in the complex mechanism of the temporomandibular joint. Every single part that belongs to the temporomandibular joint, together with the stomatognathic apparatus, plays a specific and particular role according to the dynamics and to the preservation of the correct temporomandibular joint physiology. The physiological postural and functional relationship between the various parts of the temporomandibular joint is guaranteed by a number of biomechanical restrictions that lead and influence the regular execution of the articular movements. The most involved biomechanical restrictions in the temporomandibular joint are the temporomandibular ligament, the lateral disc ligament, the bilaminar zone or retrodiscal tissue, the synovial membrane, and the synovial fluid.

  1. Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives.

    PubMed

    de Sousa, Eduardo Branco; Casado, Priscila Ladeira; Moura Neto, Vivaldo; Duarte, Maria Eugenia Leite; Aguiar, Diego Pinheiro

    2014-10-03

    Mesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts, chondroblasts, adipocytes, and even myoblasts. Most studies have focused on finding MSCs in different parts of the body for medical treatment. Every joint structure, including bone, joint fat, articular cartilage, and synovium, potentially contains resident MSCs. Recently, a progenitor cell population has been found in synovial fluid and showed similarities with both bone marrow and synovial membrane MSCs. Synovial fluid MSCs have been studied in healthy persons and osteoarthritic patients in order to explore its potential for treatment of some orthopedic disorders. Here, we briefly review the current knowledge on synovial fluid MSCs, their origin, relation to some orthopedic diseases, and future applications.

  2. The role of human xanthine oxidoreductase (HXOR), anti-HXOR antibodies, and microorganisms in synovial fluid of patients with joint inflammation.

    PubMed

    Al-Muhtaseb, Najah; Al-Kaissi, Elham; Thawaini, Abdul Jalil; Eldeen, Zuhair Muhi; Al-Muhtaseb, Sabah; Al-Saleh, Badiee

    2012-08-01

    This work is to investigate the levels of human xanthine oxidoreductase (HXOR), its antibodies, and microorganisms in synovial fluid of patients with untreated rheumatoid joint diseases. Synovial fluids were collected from sixty-four patients with rheumatoid joint diseases. Sixty-four age-matched individuals were included as control. Xanthine oxidoreductase (XOR) proteins level and anti-XOR antibodies were determined in the blood and synovial fluid, using human XOR as antigen, by enzyme-linked immunosorbent (ELISA) assay. Synovial fluids were cultured for bacteria and fungi. The titers of XOR protein in the synovial fluid of patients with rheumatoid arthritis were 90.43 ± 23.37 μg/ml (mean ± SD, n = 29) and up to 62.42 ± 8.74 μg/ml (mean ± SD, n = 35) in other joint inflammation. Anti-HXOR antibodies titers in patients were 167.72 ± 23.64 μg/ml, n = 64, which was significantly higher in rheumatoid arthritis patients. The results indicated that anti-HXOR antibodies in synovial fluids have a protective role as high concentrations against XOR were detected in inflammatory arthritis. These antibodies play a role in eliminating XOR from synovial fluids. However, immune complex formation could activate complement and participate in propagating the inflammatory cycle. Synovial aspirate ordinary microbial cultures were negative for any bacteria or fungi, but that does not exclude organisms of special culture requirements.

  3. Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases.

    PubMed

    Röhner, Eric; Matziolis, Georg; Perka, Carsten; Füchtmeier, Bernd; Gaber, Timo; Burmester, Gerd-Rüdiger; Buttgereit, Frank; Hoff, Paula

    2012-06-01

    The role of human chondrocytes in the pathogenesis of cartilage degradation in rheumatic joint diseases has presently gained increasing interest. An active chondrocyte participation in local inflammation may play a role in the initiation and progression of inflammatory joint diseases and in a disruption of cartilage repair mechanisms resulting in cartilage degradation. In the present study, we hypothesized that inflammatory synovial fluid triggers human chondrocytes to actively take part in inflammatory processes in rheumatic joint diseases. Primary human chondrocytes were incubated in synovial fluids gained from patients with rheumatoid arthritis, psoriasis arthritis and reactive arthritis. The detection of vital cell numbers was determined by using Casy Cell Counter System. Apoptosis was measured by Annexin-V and 7AAD staining. Cytokine and chemokine secretion was determined by a multiplex suspension array. Detection of vital cells showed a highly significant decrease in chondrocyte numbers. Flow cytometry demonstrated a significant increase in apoptotic chondrocytes after the incubation. An active secretion of cytokines such as MCP-1 and MIF by chondrocytes was observed. The inflammatory synovial fluid microenvironment mediates apoptosis and cell death of chondrocytes. Moreover, in terms of cytokine secretion, it also induces an active participation of chondrocytes in ongoing inflammation.

  4. Expression of interferon-gamma (IFN-δ), IL-10, IL-12 and transforming growth factor-beta (TGF-β) mRNA in synovial fluid cells from patients in the early and late phases of rheumatoid arthritis (RA)

    PubMed Central

    BUCHT, A.; LARSSON, P.; WEISBROT, L.; THORNE, C.; PISA, P.; SMEDEGÅRD, G.; KEYSTONE, E C; GRÖNBERG, A.

    1996-01-01

    The expression of immunoregulatory cytokines was investigated in freshly isolated synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) from patients with RA, using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. IFN-γ, TGF-β, IL-10 and IL-12 (p40) transcripts were detected in SFMC of patients with early disease (<1 year duration) as well as in patients with long standing arthritis (>1 year). The expression of IFN-γ, IL-10 and IL-12 mRNA was increased in SFMC compared with RA PBMC. In addition, the expression was higher in RA SFMC than in PBMC from healthy control individuals. Immunoassay analysis of the secreted IL-12 heterodimer demonstrated increased levels in RA SF compared with levels found in serum from RA patients and control individuals. High levels of TGF-β mRNA were found in SFMC, but a significantly decreased TGF-β/β2-microglobulin (β2-M) ratio was found compared with PBMC from both patients and control individuals. IL-4 mRNA could not be detected, either in SFMC or in PBMC. Cytokine expression in RA PBMC did not differ from control PBMC, with the exception of a decreased TGF-β/β2-M ratio in RA patients with early disease. Our findings of IFN-7 mRNA and IL-12, but undetectable levels of IL-4 mRNA, suggest that the synovitis is characterized by a type 1 immune response. The presence of TGF-β and IL-10 mRNA indicates that immunosuppressive cytokines may also operate in the inflamed joint, although their level of expression may not be sufficient for down-modulation of immune activation. PMID:8608632

  5. Simulation Of The Synovial Fluid In A Deformable Cavity

    NASA Astrophysics Data System (ADS)

    Martinez-Gutierrez, Nancy; Ibarra-Bracamontes, Laura A.

    2016-11-01

    The main components of a synovial joint are a cartilage and a biofluid known as the synovial fluid. The results were obtained using the FLUENT software to simulate the behavior of the synovial fluid within a deformable cavity with a simple geometry. The cartilage is represented as a porous region. By reducing the available region for the fluid, a fluid displacement into the cartilage is induced. The total pressure reached in the interface of the deformable cavity and the porous region is presented. The geometry and properties of the system are scaled to values found in a knee joint. The effect of deformation rate, fluid viscosity and properties of the porous medium on the total pressure reached are analyzed. The higher pressures are reached either for high deformation rate or when the fluid viscosity increases. This study was supported by the Mexican Council of Science and Technology (CONACyT) and by the Scientific Research Coordination of the University of Michoacan in Mexico.

  6. Secretory phospholipases A2 induce cytokine release from blood and synovial fluid monocytes.

    PubMed

    Triggiani, Massimo; Granata, Francescopaolo; Oriente, Alfonso; Gentile, Marco; Petraroli, Angelica; Balestrieri, Barbara; Marone, Gianni

    2002-01-01

    Secretory phospholipases A2 (sPLA2) are released in the blood of patients with various inflammatory diseases and exert proinflammatory activities by releasing arachidonic acid (AA), the precursor of eicosanoids. We examined the ability of four sPLA2 to activate blood and synovial fluid monocytes in vitro. Monocytes were purified from blood of healthy donors or from synovial fluid of patients with rheumatoid arthritis by negative immunoselection and by adherence to plastic dishes, respectively. The cells were incubated with group IA, IB, IIA and III sPLA2 and the release of TNF-alpha, IL-6 and IL-12 was determined by ELISA. Group IA, IB and IIA sPLA2 induced a concentration-dependent release of TNF-alpha and IL-6 from blood monocytes. These sPLA2 activated IL-12 production only in monocytes preincubated with IFN-gamma. Group IA and IIA sPLA2 also induced TNF-alpha and IL-6 release from synovial fluid monocytes. TNF-alpha and IL-6 release paralleled an increase in their mRNA expression and was independent from the capacity of sPLA2 to mobilize AA. These results indicate that sPLA2 stimulate cytokine release from blood and synovial fluid monocytes by a mechanism at least partially unrelated to their enzymatic activity. This effect may concur with the generation of AA in the proinflammatory activity of sPLA2 released during inflammatory diseases.

  7. Elevated factor J levels in synovial fluid from patients with inflammatory arthropathies.

    PubMed

    González-Rubio, C; Saboya-Palero, A; Pascual-Salcedo, D; Balsa, A; Fontán, G; López-Trascasa, M

    1997-12-01

    Factor J (FJ) is a complement inhibitor that is able to regulate in vitro both the classical and alternative human complement pathways. In the search of its biological significance, we have analyzed FJ levels in synovial fluid from patients with different arthropathies, in which IL-6 levels had been previously measured. The pathologies included in this study were: rheumatoid arthritis (RA) (n = 21), crystal deposition diseases (CDD) (n = 6), osteoarthritis (OA) (n = 23), spondyloarthritis (SpA) (n = 3) and other inflammatory arthropathies (OIA) (n = 4). We found a good correlation between IL-6 and FJ levels (r = 0.33, p = 0.0132) in the 57 processed samples. Synovial fluids had high levels of IL-6 (median: 3000 pg/ml). Besides, we found that FJ levels were elevated (241 +/- 429 micrograms/ml) when compared with NHS (5.32 +/- 2.82 micrograms/ml). Considering OA patients as control group for non-inflammatory situation, we found that FJ levels were significantly elevated in inflammatory patients only if RA patients were excluded. Furthermore, there were also significant differences with CDD patients. In addition, we have examined the presence of this inhibitor in synovial fluid by Western blot after running gels at acid pH and electrophoretical transference at the same pH. In these experiments, we evidenced the presence of a cationic protein immunoreactive with polyclonal and monoclonal anti-FJ antibodies. In conclusion, FJ levels are elevated in pathological synovial fluids. FJ could be an acute phase reactant as other molecules present in the synovial fluid, or could be shed from extracellular matrix as a consequence of the high enzymatic activity present in the articular fluid or as a response to the inflammatory stimulus.

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

    PubMed

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

    2015-05-15

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

  9. 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.

  10. Immunoregulation in arthritis. A review on synovial immune reactions in RA and in some experimental animal models for arthritis.

    PubMed

    Klareskog, L; Holmdahl, R; Goldschmidt, T; Björk, J

    1987-01-01

    Local synovial immune reactions have during recent years been characterized both in human arthritides, particularly in rheumatoid arthritis (RA), and in animal models for arthritis. Common characteristics of human RA on one hand and experimental adjuvant arthritis and collagen arthritis on the other hand, are induced expression of class II transplantation antigens on synovial cells close to the cartilage and presence of activated T lymphocytes in close proximity to these class II expressing cells. The present review aims to describe some implications of these and subsequent findings both concerning the analysis of the pathogenesis of RA and concerning some therapeutic implications derived from parallel studies on relevant features of the human RA and the respective animal models for arthritis.

  11. Articular Ankle Fracture Results in Increased Synovitis, Synovial Macrophage Infiltration, and Synovial Fluid Concentrations of Inflammatory Cytokines and Chemokines

    PubMed Central

    Furman, Bridgette D.; Kimmerling, Kelly A.; Zura, Robert D.; Reilly, Rachel M.; Zlowodzki, Michal P.; Huebner, Janet L.; Kraus, Virginia B.; Guilak, Farshid; Olson, Steven A.

    2016-01-01

    Objective The inflammatory response following an articular fracture is thought to play a role in the development of posttraumatic arthritis (PTA) but has not been well characterized. The objective of this study was to characterize the acute inflammatory response, both locally and systemically, in joint synovium, synovial fluid (SF), and serum following articular fracture of the ankle. We hypothesized that intraarticular fracture would alter the synovial environment and lead to increased local and systemic inflammation. Methods Synovial tissue biopsy specimens, SF samples, and serum samples were collected from patients with an acute articular ankle fracture (n = 6). Additional samples (normal, ankle osteoarthritis [OA], and knee OA [n = 6 per group]) were included for comparative analyses. Synovial tissue was assessed for synovitis and macrophage count. SF and serum were assessed for cytokines (interferon-γ [IFNγ], interleukin-1β [IL-1β], IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor α) and chemokines (eotaxin, eotaxin 3, IFNγ-inducible 10-kd protein, monocyte chemotactic protein 1 [MCP-1], MCP-4, macrophage-derived chemokine, macrophage inflammatory protein 1β, and thymus and activation–regulated chemokine). Results Synovitis scores were significantly higher in ankle fracture tissue compared with normal ankle tissue (P = 0.007), and there was a trend toward an increased abundance of CD68+ macrophages in ankle fracture synovium compared with normal knee synovium (P = 0.06). The concentrations of all cytokines and chemokines were elevated in the SF of patients with ankle fracture compared with those in SF from OA patients with no history of trauma. Only the concentration of IL-6 was significantly increased in the serum of patients with ankle fracture compared with normal serum (P = 0.027). Conclusion Articular fracture of the ankle increased acute local inflammation, as indicated by increased synovitis, increased macrophage infiltration into

  12. 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.

  13. Tuberculosis diagnosed by PCR analysis of synovial fluid.

    PubMed

    Fujimoto, Nobukazu; Gemba, Kenichi; Yao, Atsushi; Ozaki, Shinji; Ono, Katsuichiro; Wada, Sae; Fujii, Yasuhiro; Namba, Yoshifumi; Kishimoto, Takumi

    2010-02-01

    Tuberculosis is a leading cause of mortality due to an infectious agent worldwide. It often affects multiple organs by hematogenous spread of Mycobacterium tuberculosis, but knee-joint involvement is extremely rare, comprising approximately 0.1% of all forms of tuberculosis. We present a case of tuberculous pleuritis with knee-joint involvement. Cytological and biochemical analysis of the pleural fluid and a biopsy specimen of the cervical lymph node indicated tuberculosis, but a definitive diagnosis was not given. A confirmed diagnosis was finally obtained through PCR analysis of the synovial fluid. Tuberculosis should be included in the differential diagnosis in patients with persistent pain and swelling of the knee. PCR analysis of the synovial fluid is a quick and useful method for the diagnosis.

  14. S100A8/A9 as a biomarker for synovial inflammation and joint damage in patients with rheumatoid arthritis.

    PubMed

    Kang, Kwi Young; Woo, Jung-Won; Park, Sung-Hwan

    2014-01-01

    S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inflammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.

  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. TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis

    PubMed Central

    Spreafico, Roberto; Consolaro, Alessandro; Leong, Jing Yao; Chua, Camillus; Massa, Margherita; Saidin, Suzan; Magni-Manzoni, Silvia; Arkachaisri, Thaschawee; Wallace, Carol A; Gattorno, Marco; Martini, Alberto; Lovell, Daniel J; Albani, Salvatore

    2017-01-01

    Objectives The imbalance between effector and regulatory T (Treg) cells is crucial in the pathogenesis of autoimmune arthritis. Immune responses are often investigated in the blood because of its accessibility, but circulating lymphocytes are not representative of those found in inflamed tissues. This disconnect hinders our understanding of the mechanisms underlying disease. Our goal was to identify Treg cells implicated in autoimmunity at the inflamed joints, and also readily detectable in the blood upon recirculation. Methods We compared Treg cells of patients with juvenile idiopathic arthritis responding or not to therapy by using: (i) T cell receptor (TCR) sequencing, to identify clonotypes shared between blood and synovial fluid; (ii) FOXP3 Treg cell-specific demethylated region DNA methylation assays, to investigate their stability and (iii) flow cytometry and suppression assays to probe their tolerogenic functions. Results We found a subset of synovial Treg cells that recirculated into the bloodstream of patients with juvenile idiopathic and adult rheumatoid arthritis. These inflammation-associated (ia)Treg cells, but not other blood Treg cells, expanded during active disease and proliferated in response to their cognate antigens. Despite the typical inflammatory-skewed balance of immune mechanisms in arthritis, iaTreg cells were stably committed to the regulatory lineage and fully suppressive. A fraction of iaTreg clonotypes were in common with pathogenic effector T cells. Conclusions Using an innovative antigen-agnostic approach, we uncovered a population of bona fide synovial Treg cells readily accessible from the blood and selectively expanding during active disease, paving the way to non-invasive diagnostics and better understanding of the pathogenesis of autoimmunity. PMID:27311837

  17. 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

  18. Expression and citrullination of keratin in synovial tissue of rheumatoid arthritis.

    PubMed

    Chang, Xiaotian; Jian, Xiangdong; Yan, Xinfeng

    2009-09-01

    Keratin is the main component of cellular intermediate filaments, and its post-translational modification plays an important role in cell differentiation and apoptosis, as well as disease states. The conversion of peptidylarginine to citrulline, termed citrullination, is particularly involved in the pathogenesis of rheumatoid arthritis (RA). Immunohistochemistry using an antibody mixture that broadly recognized various keratin forms detected cytokeratin in many cells in the area lining the synovial membrane of RA. Furthermore, double immuno-florescent labeling showed that the cells expressing cytokeratin were also positive for citrulline when they were in the vicinity of extracellular deposits or approached the exterior of the synovial membrane. Western blot analysis demonstrated citrullination of keratin purified from RA synovial tissue by immuno-precipitation. The above results indicate the presence of citrullinated cytokeratin in synovial membranes in RA.

  19. Synovial biopsy

    MedlinePlus

    ... such as rheumatoid arthritis, or uncommon infections like tuberculosis. Normal Results The synovial membrane structure is normal. ... that affects the skin, joints, and other organs) Tuberculosis Synovial cancer (very rare type of soft tissue ...

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

    PubMed

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

    1990-12-01

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

  1. Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis

    PubMed Central

    Nikitopoulou, Ioanna; Oikonomou, Nikos; Karouzakis, Emmanuel; Sevastou, Ioanna; Nikolaidou-Katsaridou, Nefeli; Zhao, Zhenwen; Mersinias, Vassilis; Armaka, Maria; Xu, Yan; Masu, Masayuki; Mills, Gordon B.; Gay, Steffen; Kollias, George

    2012-01-01

    Rheumatoid arthritis is a destructive arthropathy characterized by chronic synovial inflammation that imposes a substantial socioeconomic burden. Under the influence of the proinflammatory milieu, synovial fibroblasts (SFs), the main effector cells in disease pathogenesis, become activated and hyperplastic, releasing proinflammatory factors and tissue-remodeling enzymes. This study shows that activated arthritic SFs from human patients and animal models express significant quantities of autotaxin (ATX; ENPP2), a lysophospholipase D that catalyzes the conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA). ATX expression from SFs was induced by TNF, and LPA induced SF activation and effector functions in synergy with TNF. Conditional genetic ablation of ATX in mesenchymal cells, including SFs, resulted in disease attenuation in animal models of arthritis, establishing the ATX/LPA axis as a novel player in chronic inflammation and the pathogenesis of arthritis and a promising therapeutic target. PMID:22493518

  2. Expression of MicroRNA-146 in Rheumatoid Arthritis Synovial Tissue

    PubMed Central

    Nakasa, Tomoyuki; Miyaki, Shigeru; Okubo, Atsuko; Hashimoto, Megumi; Nishida, Keiichiro; Ochi, Mitsuo; Asahara, Hiroshi

    2009-01-01

    Objective Several microRNA, which are ~22-nucleotide noncoding RNAs, exhibit tissue-specific or developmental stage–specific expression patterns and are associated with human diseases. The objective of this study was to identify the expression pattern of microRNA-146 (miR-146) in synovial tissue from patients with rheumatoid arthritis (RA). Methods The expression of miR-146 in synovial tissue from 5 patients with RA, 5 patients with osteoarthritis (OA), and 1 normal subject was analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR) and by in situ hybridization and immunohistochemistry of tissue sections. Induction of miR-146 following stimulation with tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT-PCR. Results Mature miR-146a and primary miR-146a/b were highly expressed in RA synovial tissue, which also expressed TNFα, but the 2 microRNA were less highly expressed in OA and normal synovial tissue. In situ hybridization showed primary miR-146a expression in cells of the superficial and sublining layers in synovial tissue from RA patients. Cells positive for miR-146a were primarily CD68+ macrophages, but included several CD3+ T cell subsets and CD79a+ B cells. Expression of miR-146a/b was markedly up-regulated in RASFs after stimulation with TNFα and IL-1β. Conclusion This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFα and IL-1β. Further studies are required to elucidate the function of miR-146 in these tissues. PMID:18438844

  3. Rheumatoid synovial fluid T cells are sensitive to APO2L/TRAIL.

    PubMed

    Martínez-Lorenzo, María José; Anel, Alberto; Saez-Gutierrez, Berta; Royo-Cañas, María; Bosque, Alberto; Alava, María Angeles; Piñeiro, Andrés; Lasierra, Pilar; Asín-Ungría, Jaime; Larrad, Luis

    2007-01-01

    The infiltration and accumulation of T cells in the rheumatoid arthritis (RA) synovial fluid (SF) are hallmarks of disease. We aimed to assess the functional relevance of FasL and of APO2L/TRAIL in the persistence of T cells in the rheumatoid SF. We have analyzed the expression of the activation markers HLA-DR and CD69 and also of the death receptor Fas/CD95 and death ligands FasL or APO2L/TRAIL in CD3+ lymphocytes from SF of 62 RA patients, together with their sensitivity to anti-Fas mAb or to rAPO2L/TRAIL, using as controls T lymphocytes present in SF of 20 patients with traumatic arthritis. T lymphocytes infiltrated in SF of RA patients have a chronically activated phenotype, but they are resistant to Fas-induced toxicity. However, they are more susceptible to rAPO2L/TRAIL than T cells in the SF of traumatic arthritis patients. In addition, we found very low amounts of bioactive FasL and APO2L/TRAIL associated with exosomes in SF from RA patients as compared with SF from traumatic arthritis patients. The observation on the sensitivity of RA SF T cells to rAPO2L could have therapeutic implications because bioactive APO2L/TRAIL could be beneficial as a RA treatment.

  4. The value of synovial fluid assays in the diagnosis of joint disease: a literature survey

    PubMed Central

    Swan, A; Amer, H; Dieppe, P

    2002-01-01

    Objective: To carry out a critical appraisal of the literature in an attempt to assess the current value of synovial fluid (SF) analysis in the diagnosis of joint disease. Methods: A literature search was undertaken using the Medline, Biomed, Bids, Pubmed, and Embase electronic databases using the keywords: synovial fluid (SF) analysis, SF crystals, joint sepsis, acute arthritis, and SF cell counts, cytology, biomarkers, and microbiology. Results: Publications fell into three main categories. Firstly, reports assessing the value of the three traditional assays (microbiology, white blood cell counts, and microscopy for pathogenic crystals). For these quality control evidence was found to be sparse, and tests for sensitivity, specificity, and reliability showed worrying variations. These poor standards in SF analysis may be due to lack of inclusion of some tests within routine pathology services. Secondly, claims for the usefulness of "new" assays (cytology and biochemical markers). For cytology, the supporting evidence was mainly anecdotal and there were no reports on specificity, sensitivity, and reliability. Interpretation difficulties are a major hindrance to the clinical use of biochemical assays, which remain primarily research tools. Finally, work on the diagnostic value of SF analysis in general. The appraisal confirmed that SF analysis remains of major diagnostic value in acute arthritis, where septic arthritis or crystal arthropathy is suspected, and in intercritical gout. Conclusions: Given the importance of SF tests, rationalisation of their use, together with improved quality control, should be immediate priorities. Further investigation is recommended into the contribution of SF inspection and white cell counts to diagnosis, as well as of the specificity and sensitivity of SF microbiological assays, crystal identification, and cytology. PMID:12006320

  5. 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

  6. A Case of Rheumatoid Arthritis with Unilateral Knee Synovial Hypertrophy in Hemiplegia

    PubMed Central

    Kim, Chan Woo; Kim, Mi Jung; Park, Si Bog

    2012-01-01

    A 64-year-old woman suffering right hemiplegia came in with pain and swelling on her left knee, general weakness and poor oral intake for 2 months. On physical examination we were able to palpate a mass with irregular margin around the left suprapatellar area. From the results of the magnetic resonance imaging (MRI), synovial proliferative disease, infectious arthritis, or gouty arthritis was suspected. We performed a blood laboratory test to detect rheumatologic diseases, knee joint aspiration, and bone scan for differential diagnosis, and were able to diagnose rheumatoid arthritis (RA) from the results of blood laboratory, physical examination, and bone scan. Consequently, we started medications for controlling RA. Herein, we report a case of rheumatoid arthritis with unilateral knee synovial hypertrophy in hemiplegia. If a right hemiplegic patient has recurrent pain on the left knee and synovial hypertrophy, and fails to respond to treatment for osteoarthritis, early detection by evaluation for rheumatic disease is crucial to prevent severe sequelae influencing rehabilitation of hemiplegia. PMID:22506248

  7. A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheumatoid arthritis.

    PubMed

    Woods, James M; Klosowska, Karolina; Spoden, Darrin J; Stumbo, Nataliya G; Paige, Douglas J; Scatizzi, John C; Volin, Michael V; Rao, Malathi S; Perlman, Harris

    2006-01-01

    Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and destruction of cartilage and bone. The fibroblast-like synoviocyte (FLS) population is central to the development of pannus by migrating into cartilage and bone. We demonstrated previously that expression of the cell cycle inhibitor p21 is significantly reduced in RA synovial lining, particularly in the FLS. The aim of this study was to determine whether reduced expression of p21 in FLS could alter the migratory behavior of these cells. FLS were isolated from mice deficient in p21 (p21(-/-)) and were examined with respect to growth and migration. p21(-/-) and wild-type (WT) FLS were compared with respect to migration towards chemoattractants found in RA synovial fluid in the presence and absence of cell cycle inhibitors. Restoration of p21 expression was accomplished using adenoviral infection. As anticipated from the loss of a cell cycle inhibitor, p21(-/-) FLS grow more rapidly than WT FLS. In examining migration towards biologically relevant RA synovial fluid, p21(-/-) FLS display a marked increase (3.1-fold; p < 0.05) in migration compared to WT cells. Moreover, this effect is independent of the cell cycle since chemical inhibitors that block the cell cycle have no effect on migration. In contrast, p21 is required to repress migration as restoration of p21 expression in p21(-/-) FLS reverses this effect. Taken together, these data suggest that p21 plays a novel role in normal FLS, namely to repress migration. Loss of p21 expression that occurs in RA FLS may contribute to excessive invasion and subsequent joint destruction.

  8. Bone Morphogenetic Protein 2 and Transforming Growth Factor β1 Inhibit the Expression of the Proinflammatory Cytokine IL-34 in Rheumatoid Arthritis Synovial Fibroblasts.

    PubMed

    Chemel, Marguerite; Brion, Regis; Segaliny, Aude-Isabelle; Lamora, Audrey; Charrier, Celine; Brulin, Benedicte; Maugars, Yves; Le Goff, Benoit; Heymann, Dominique; Verrecchia, Franck

    2017-01-01

    IL-34 is a proinflammatory cytokine implicated in rheumatoid arthritis (RA). The current study aimed to assess the IL-34 expression in response to two members of the transforming growth factor (TGF)-β family, TGF-β1 and bone morphogenetic protein (BMP)-2, in synovial fibroblasts from RA patients. IL-34, TGF-β1, and BMP-2 productions were measured in patient synovial fluids by enzyme-linked immunosorbent assay. IL-34 mRNA levels were quantified by real-time quantitative PCR in human synovial fibroblasts and murine mesenchymal stem cells. Pharmacologic inhibitions were used to determine the involvement of activin receptor-like kinase 1 (ALK1) and ALK5 downstream TGF-β1 and BMP-2. IL-34, TGF-β1, and BMP-2 were expressed in synovial fluids from RA patients. We found a significant correlation between IL-34 and TGF-β1 expressions. Levels of both IL-34 and TGF-β1 were thus correlated with the total leukocyte counts in the synovial fluids. TGF-β1 and BMP-2 decreased IL-34 expression in the synovial fibroblasts or in murine mesenchymal stem cells in a dose- and time-dependent manner through ALK5 and ALK1 pathways, respectively. In addition, TGF-β1 and BMP-2 antagonized tumor necrosis factor α-induced IL-34 gene expression. This work identifies TGF-β1 and BMP-2 as potent inhibitors of IL-34 expression in RA synovial fibroblasts. These cytokines, as upstream inhibitors of IL-34, may thus contribute to antagonize inflammation and bone erosions in RA.

  9. 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

  10. 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.

  11. [Inhibition of expontaneous cytotoxicity and antibody dependency by rheumatoid synovial fluid].

    PubMed

    Noguera Hernando, E; Kreisler, M; Durantez, A; Larrea Gayarre, A; de Landazuri, M O; Cruz Martínez, J

    1978-01-01

    A number of authors have pointed out a diminution of ADCC (Antibody dependent cellular cytotoxicity) in lymphocytes from peripheral blood of patients with rheumatoid arthritis (RA). It has also been found that the addition of rheumatoid serum inhibits ADCC and also spontaneous cellular cytotoxicity (SCC). This effect could be the result of blocking of effector cell receptors for the Fc fragment of IgG by anti-immunoglobulins and/or immune complexes, present in great quantities in rheumatoid serum. We investigated the effect of synovial fluid on the ADCC and SCC shown by purified suspensions of lymphocytes from healthy donors and RA patients towards chicken erythrocytes tagged with 51 Cr. The samples of synovial fluid from patients with RA or arthrosis did not influence per se the spontaneous release of 51 Cr, once their complement had been removed. Seven-eight of the rheumatoid synovial fluid (RSF) produced a significant decline (p less than 0.01) of SCC. Lymphocytes from the peripheral blood of RA patients showed a greater decline in SCC after the addition of RSF than those from healthy subjects (p less than 0.02). In 14/16 RSF and 5/7 samples of arthrosis synovial fluid (ASF) the ability to diminish ADCC significantly (P less than 0.01) was shown. RSF maintained this inhibitory effect in 1:40 and 1:80 dilutions, whereas in these conditions ASF had no effect on ADCC. RSF and ASF, before their complement was removed, showed an opposite effect, provoking an increase in cytotoxic activity, both SCC and ADCC, though in different proportions. These experiments show that RSF, like rheumatoid serum, inhibits ADCC and SCC, possibly by the same mechanism which blocks the Fc receptors by means of immune complexes, and coincides in its general lines with the recent findings of Díaz Jouanen et al. The pathogenetic implications of this phenomenon are difficult to clarify at present. Its occurrence in vivo would represent the establishment of a local block of cytotoxic

  12. Inactivation of synovial fluid alpha 1-antitrypsin by exercise of the inflamed rheumatoid joint.

    PubMed

    Zhang, Z; Farrell, A J; Blake, D R; Chidwick, K; Winyard, P G

    1993-04-26

    alpha 1-Antitrypsin (alpha 1AT) is known to be oxidised by reactive oxygen species both in vitro and in vivo, leading to its inactivation. We report here that synovial fluid (SF) alpha 1AT is inactivated during exercise of the knee-joints of rheumatoid arthritis (RA) patients. Sequential SF sampling from exercised RA patients showed a marked decrease in the mean activity of alpha 1AT after exercise with no change in the molecular forms of alpha 1AT. No such inactivation was found in the control (continuously resting) RA patients. We suggest that oxidation may contribute to alpha 1AT inactivation as a consequence of 'hypoxic-reperfusion' injury after exercise of the inflamed joint.

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2017-03-01

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

  15. Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints

    PubMed Central

    Busso, N.; Peclat, V.; So, A.; Sappino, A.

    1997-01-01

    OBJECTIVE—To analyse the functional activity of the plasminogen activators urokinase (uPA) and tissue type plasminogen activator (tPA) in human synovial membrane, and to compare the pattern of expression between normal, osteoarthritic, and rheumatoid synovium. The molecular mechanisms underlying differences in PA activities between normal and pathological synovial tissues have been further examined.
METHODS—Synovial membranes from seven normal (N) subjects, 14 osteoarthritis (OA), and 10 rheumatoid arthritis (RA) patients were analysed for plasminogen activator activity by conventional zymography and in situ zymography on tissue sections. The tissue distribution of uPA, tPA, uPA receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) was studied by immunohistochemistry. uPA, tPA, uPAR, and PAI-1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively.
RESULTS—All normal and most OA synovial tissues expressed predominantly tPA catalysed proteolytic activity mainly associated to the synovial vasculature. In some OA, tPA activity was expressed together with variable amounts of uPA mediated activity. By contrast, most RA synovial tissues exhibited considerably increased uPA activity over the proliferative lining areas, while tPA activity was reduced when compared with N and OA synovial tissues. This increase in uPA activity was associated with increased levels of uPA antigen and its corresponding mRNA, which were localised over the synovial proliferative lining areas. In addition, in RA tissues, expression of the specific uPA receptor (uPAR) and of the plasminogen activator inhibitor-type 1 (PAI-1) were also increased.
CONCLUSION—Taken together, these results show an alteration of the PA/plasmin system in RA synovial tissues, resulting in increased uPA catalytic activity that may play a part in tissue destruction in RA.

 PMID:9370880

  16. 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.

  17. Sonographic synovial vascularity of synovitis in rheumatoid arthritis.

    PubMed

    Fukae, Jun; Tanimura, Kazuhide; Atsumi, Tatsuya; Koike, Takao

    2014-04-01

    RA is a condition of multiple synovitis. Abnormal synovial vascularity (SV) is evident with the onset of joint inflammation. The idea of estimating the level of joint inflammation by sonographic SV was conceived with the advancement of US. The ideal treatment strategy, called treat to target (T2T), requires early diagnosis and assessment of RA. Detection of positive SV can be useful for proving the presence of synovitis and finally diagnosing RA. In the assessment of RA, US-based global scores aimed at assessing overall disease activity have the potential to be useful for the achievement of T2T because US can directly detect changes in synovitis. Remaining SV in local joints increases the risk of structural deterioration. RA requires both improvement of overall disease activity and the disappearance of local SV for remission. The evaluation of SV provides various information and contributes to the clinical treatment of RA.

  18. Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions.

    PubMed Central

    Xu, W D; Firestein, G S; Taetle, R; Kaushansky, K; Zvaifler, N J

    1989-01-01

    A liquid culture technique was used to study 23 synovial fluids (SF) (21 from inflammatory joint diseases and 2 noninflammatory SF) and supernatants of two cultured rheumatoid arthritis (RA) synovial tissues for colony-stimulating factor (CSF). The proliferative responses of human peripheral blood macrophage-depleted non-T cells treated with synovial fluids, supernatants of synovial tissue explants, and recombinant granulocyte-macrophage (rGM)-CSF were compared. Aggregates of cells that formed in long-term cultures (15 d) were similar for each applied agent and consisted of macrophages, eosinophils, and large blasts. Tritiated thymidine incorporation was proportional to the concentration of rGM-CSF and was accompanied by an increase in number and size of cellular aggregates formed in the cultures. CSF activity was observed in inflammatory SF, with tritiated thymidine uptake of 3,501 +/- 1,140 cpm in the presence of RA samples (n = 15) compared to 1,985 +/- 628 for non-RA inflammatory SF (n = 7) (P less than 0.05) and 583 +/- 525 for medium (n = 6) (P less than 0.01). The proliferative response to RA SF was often more apparent when the samples were diluted, because at higher concentrations the RA SF was inhibitory. Two RA SF were fractionated by Sephadex G100 column chromatography; low levels of CSF activity were detected in fractions corresponding to Mr of 70-100 kD, but the major CSF activity was found in the 20-24-kD fractions. A polyclonal rabbit anti-GM-CSF antibody eliminated the stimulating activity from both rGM-CSF and RA SF. Finally, a specific RIA identified significant levels of GM-CSF (40-140 U/ml) in the culture supernatants of 3 additional RA synovial tissues. These data document the local production of GM-CSF in rheumatoid synovitis and are the first description of this cytokine at a site of disease activity. Images PMID:2646320

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2001-01-01

    To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis. PMID:11207665

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

    PubMed

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

    2001-02-01

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

  2. Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein

    PubMed Central

    Senolt, L; Braun, M; Olejarova, M; Forejtova, S; Gatterova, J; Pavelka, K

    2005-01-01

    Background: Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders—for example, rheumatoid arthritis. Objective: To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)—a marker of articular cartilage destruction. Methods: Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA. Results: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease. Conclusion: Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker. PMID:15897309

  3. 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.

  4. High synovial expression of the inhibitory FcγRIIb in rheumatoid arthritis

    PubMed Central

    Magnusson, Sofia E; Engström, Marianne; Jacob, Uwe; Ulfgren, Ann-Kristin; Kleinau, Sandra

    2007-01-01

    Activating Fc gamma receptors (FcγRs) have been identified as having important roles in the inflammatory joint reaction in rheumatoid arthritis (RA) and murine models of arthritis. However, the role of the inhibitory FcγRIIb in the regulation of the synovial inflammation in RA is less known. Here we have investigated synovial tissue from RA patients using a novel monoclonal antibody (GB3) specific for the FcγRIIb isoform. FcγRIIb was abundantly expressed in synovia of RA patients, in sharp contrast to the absence or weak staining of FcγRIIb in synovial biopsies from healthy volunteers. In addition, the expression of FcγRI, FcγRII and FcγRIII was analyzed in synovia obtained from early and late stages of RA. Compared with healthy synovia, which expressed FcγRII, FcγRIII but not FcγRI, all activating FcγRs were expressed and significantly up-regulated in RA, regardless of disease duration. Macrophages were one of the major cell types in the RA synovium expressing FcγRIIb and the activating FcγRs. Anti-inflammatory treatment with glucocorticoids reduced FcγR expression in arthritic joints, particularly that of FcγRI. This study demonstrates for the first time that RA patients do not fail to up-regulate FcγRIIb upon synovial inflammation, but suggests that the balance between expression of the inhibitory FcγRIIb and activating FcγRs may be in favour of the latter throughout the disease course. Anti-inflammatory drugs that target activating FcγRs may represent valuable therapeutics in this disease. PMID:17521421

  5. High synovial expression of the inhibitory FcgammaRIIb in rheumatoid arthritis.

    PubMed

    Magnusson, Sofia E; Engström, Marianne; Jacob, Uwe; Ulfgren, Ann-Kristin; Kleinau, Sandra

    2007-01-01

    Activating Fc gamma receptors (FcgammaRs) have been identified as having important roles in the inflammatory joint reaction in rheumatoid arthritis (RA) and murine models of arthritis. However, the role of the inhibitory FcgammaRIIb in the regulation of the synovial inflammation in RA is less known. Here we have investigated synovial tissue from RA patients using a novel monoclonal antibody (GB3) specific for the FcgammaRIIb isoform. FcgammaRIIb was abundantly expressed in synovia of RA patients, in sharp contrast to the absence or weak staining of FcgammaRIIb in synovial biopsies from healthy volunteers. In addition, the expression of FcgammaRI, FcgammaRII and FcgammaRIII was analyzed in synovia obtained from early and late stages of RA. Compared with healthy synovia, which expressed FcgammaRII, FcgammaRIII but not FcgammaRI, all activating FcgammaRs were expressed and significantly up-regulated in RA, regardless of disease duration. Macrophages were one of the major cell types in the RA synovium expressing FcgammaRIIb and the activating FcgammaRs. Anti-inflammatory treatment with glucocorticoids reduced FcgammaR expression in arthritic joints, particularly that of FcgammaRI. This study demonstrates for the first time that RA patients do not fail to up-regulate FcgammaRIIb upon synovial inflammation, but suggests that the balance between expression of the inhibitory FcgammaRIIb and activating FcgammaRs may be in favour of the latter throughout the disease course. Anti-inflammatory drugs that target activating FcgammaRs may represent valuable therapeutics in this disease.

  6. Dynamics of Early Synovial Cytokine Expression in Rodent Collagen-Induced Arthritis

    PubMed Central

    Palmblad, Karin; Erlandsson-Harris, Helena; Tracey, Kevin J.; Andersson, Ulf

    2001-01-01

    This study was performed to elucidate pathophysiological events before and during the course of collagen-induced arthritis in Dark Agouti rats, a model for rheumatoid arthritis. Kinetic studies of local cytokine responses were determined using immunohistochemical techniques, quantified by computer-assisted image analysis. We recently reported that the macrophage-pacifying agent CNI-1493 successfully ameliorated collagen-induced arthritis. In the present trial, we investigated the potential of CNI-1493 to down-regulate pro-inflammatory cytokines. Synovial cryosections were analyzed at various time points for the presence of interleukin (IL)-1β, tumor necrosis factor (TNF), and transforming growth factor (TGF)-β. Unexpectedly, an early simultaneous TNF and IL-1β expression was detected in resident cells in the lining layer, preceding disease onset and inflammatory cell infiltration by >1 week. The predominant cytokine synthesis by synovial (ED1+) macrophages coincided with clinical disease. TNF production greatly exceeded that of IL-1β. CNI-1493 treatment did not affect the early disease-preceding TNF and IL-1β synthesis in the lining layer. However, after disease onset, CNI-1493 intervention resulted in a pronounced reduced IL-1β and in particular TNF expression. Furthermore, CNI-1493 significantly up-regulated synthesis of the anti-inflammatory cytokine TGF-β and thereby shifted the balance of pro-inflammatory and anti-inflammatory cytokines in the arthritic joint in a beneficial way. PMID:11159186

  7. 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.

  8. 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.

  9. Synovial fluid lubrication of artificial joints: protein film formation and composition.

    PubMed

    Fan, Jingyun; Myant, Connor; Underwood, Richard; Cann, Philippa

    2012-01-01

    Despite design improvements, wear of artificial implants remains a serious health issue particularly for Metal-on-Metal (MoM) hips where the formation of metallic wear debris has been linked to adverse tissue response. Clearly it is important to understand the fundamental lubrication mechanisms which control the wear process. It is usually assumed that MoM hips operate in the ElastoHydrodynamic Lubrication (EHL) regime where film formation is governed by the bulk fluid viscosity; however there is little experimental evidence of this. The current paper critically examines synovial fluid lubrication mechanisms and the effect of synovial fluid chemistry. Two composition parameters were chosen; protein content and pH, both of which are known to change in diseased or post-operative synovial fluid. Film thickness and wear tests were carried out for a series of model synovial fluid solutions. Two distinct film formation mechanisms were identified; an adsorbed surface film and a high-viscosity gel. The entrainment of this gel controls film formation particularly at low speeds. However wear of the femoral head still occurs and this is thought to be due primarily to a tribo-corrosion mechanisms. The implications of this new lubrication mechanism and the effect of different synovial fluid chemistries are examined. One important conclusion is that patient synovial fluid chemistry plays an important role in determining implant wear and the likelihood of failure.

  10. The combined effects of anti-TNFalpha antibody and IL-1 receptor antagonist in human rheumatoid arthritis synovial membrane.

    PubMed

    Hosaka, Kunihiro; Ryu, Junnosuke; Saitoh, Shu; Ishii, Takao; Kuroda, Kazumichi; Shimizu, Kazufumi

    2005-12-21

    TNFalpha and IL-1 are the pivotal cytokines involved in rheumatoid arthritis (RA). More recently, the biological therapy targeting TNFalpha or IL-1 has been impressively effective for many RA patients, however, it remains insufficient in some patients. In the present study, we examined the combined effects of two agents against TNFalpha and IL-1 in human RA synovial membrane. Synovial explants (an ex vivo model) and synovial fibroblasts (an in vitro model) were prepared from 11 RA patients, and then anti-TNFalpha antibody (Anti-TNFalpha) and IL-1 receptor antagonist (IL-1Ra), either alone or in combination, were added to the synovial explants and fibroblasts. IL-6 and MMP-3 production were measured after incubation. As a result, their production significantly decreased by the combination of agents compared with the control group in both the synovial explants and fibroblasts. The efficacy of this combination was also observed for IL-6 production compared with each agent alone in the synovial explants, and for IL-6 and MMP-3 production compared with each agent alone in the synovial fibroblasts. Therefore, the combination of Anti-TNFalpha and IL-1Ra appears more beneficial in synovial membrane, particularly when compared with a single agent alone.

  11. Cytoskeletal Rearrangements in Synovial Fibroblasts as a Novel Pathophysiological Determinant of Modeled Rheumatoid Arthritis

    PubMed Central

    Aidinis, Vassilis; Carninci, Piero; Armaka, Maria; Witke, Walter; Harokopos, Vaggelis; Pavelka, Norman; Koczan, Dirk; Argyropoulos, Christos; Thwin, Maung-Maung; Möller, Steffen; Kazunori, Waki; Gopalakrishnakone, Ponnampalam; Ricciardi-Castagnoli, Paola; Thiesen, Hans-Jürgen; Hayashizaki, Yoshihide; Kollias, George

    2005-01-01

    Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well-recognized tumour necrosis factor-driven animal model of this disease and performed high-throughput expression profiling with subtractive cDNA libraries and oligonucleotide microarray hybridizations, coupled with independent statistical analysis. This twin approach was validated by a number of different methods in other animal models of arthritis as well as in human patient samples, thus creating a unique list of disease modifiers of potential therapeutic value. Importantly, and through the integration of genetic linkage analysis and Gene Ontology–assisted functional discovery, we identified the gelsolin-driven synovial fibroblast cytoskeletal rearrangements as a novel pathophysiological determinant of the disease. PMID:16254600

  12. Succinate/NLRP3 Inflammasome Induces Synovial Fibroblast Activation: Therapeutical Effects of Clematichinenoside AR on Arthritis

    PubMed Central

    Li, Yi; Zheng, Jia-Yi; Liu, Jian-Qun; Yang, Jie; Liu, Yang; Wang, Chen; Ma, Xiao-Nan; Liu, Bao-Lin; Xin, Gui-Zhong; Liu, Li-Fang

    2016-01-01

    Clematichinenoside AR (C-AR) is a triterpene saponin isolated from the root of Clematis manshurica Rupr., which is a herbal medicine used in traditional Chinese medicine for the treatment of arthritis. C-AR exerts anti-inflammatory and immunosuppressive properties, but little is known about its action in the suppression of fibroblast activation. Low oxygen tension and transforming growth factor-β (TGF-β1) induction in the synovium contribute to fibrosis in arthritis. This study was designed to investigate the effect of C-AR on synovial fibrosis from the aspects of hypoxic TGF-β1 and hypoxia-inducible transcription factor-1α (HIF-1α) induction. In the synovium of rheumatoid arthritis (RA) rats, hypoxic TGF-β1 induction increased succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation and induced NLRP3 inflammasome activation in a manner dependent on HIF-1α induction. In response to NLRP3 inflammasome activation, the released IL-1β further increased TGF-β1 induction, suggesting the forward cycle between inflammation and fibrosis in myofibroblast activation. In the synovium of RA rats, C-AR inhibited hypoxic TGF-β1 induction and suppressed succinate-associated NLRP3 inflammasome activation by inhibiting SDH activity, and thereby prevented myofibroblast activation by blocking the cross-talk between inflammation and fibrosis. Taken together, these results showed that succinate worked as a metabolic signaling, linking inflammation with fibrosis through NLRP3 inflammasome activation. These findings suggested that synovial succinate accumulation and HIF-1α induction might be therapeutical targets for the prevention of fibrosis in arthritis. PMID:28003810

  13. Loading-induced changes in synovial fluid affect cartilage metabolism.

    PubMed

    Van den Hoogen, B M; van de Lest, C H; van Weeren, P R; Lafeber, F P; Lopes-Cardozo, M; van Golde, L M; Barneveld, A

    1998-06-01

    The purpose of this study was to determine whether changes in the synovial fluid (SF) induced by in vivo loading can induce an alteration in the metabolic activity of chondrocytes in vitro. Therefore, SF was collected from ponies after a period of box rest and after they had exercise for a week. Normal, unloaded articular cartilage explants were cultured in 20% solutions of these SFs for 4 days and chondrocyte activity was determined by glycosaminoglycan (GAG) turnover. In explants cultured in post-exercise SF, GAG synthesis was enhanced and GAG release was diminished when compared to cultures in pre-exercise SF. SF analysis showed that levels of insulin-like growth factors (IGF-I and IGF-II) tended to be higher in post-exercise SF, while no differences were found in metalloproteinase activity, hyaluronic acid and protein concentrations. This study showed that anabolic effects of joint loading on cartilage are, at least partially, mediated by alterations in the SF.

  14. Pathologic finding of increased expression of interleukin-17 in the synovial tissue of rheumatoid arthritis patients

    PubMed Central

    Li, Ning; Wang, Jun C; Liang, Toong H; Zhu, Ming H; Wang, Jia Y; Fu, Xue L; Zhou, Jie R; Zheng, Song G; Chan, Paul; Han, Jie

    2013-01-01

    Rheumatoid arthritis (RA) is a common autoimmune disease of chronic systemic inflammatory disorder that will affect multiple tissues and organs such as skin, heart or lungs; but it principally attacks the joints, producing a nonsuppurative inflammatory and proliferative synovitis that often progresses to major damaging of articular cartilage and joint ankylosis. Although the definite etiology is still unknown, recent studies suggest that T-helper cells (Th17) may play a pivotal role in the pathogenesis of RA. And interleukin-17 (IL-17), which is a cytokine of Th17 cells, may be a key factor in the occurrence of RA. The binding of IL-17 to specific receptor results in the expression of fibroblasts, endothelial and epithelial cells and also synthesis of several major factors such as tumor necrosis factor alpha (TNF-α), IL-1β that result in the structural damage of RA joints. Though some previous studies have shown that IL-17 exists in the synovium of RA, few has definite proof quantitatively by pathology about its existence in synovial membrane. This study comprised of 30 RA patients and 10 healthy control, pathologic study of the synovial membrane showed increased expression of IL-17 in the synovial tissue of RA patients, the intensity is compatible with clinical severity of disease as validated by DAS28 score and disease duration. Northern blot study also confirmed the increased expression of IL-17 in the synovial tissues. This study sheds further light that IL-17 may be a key factor in the pathogenesis of RA and a determinant of disease severity. PMID:23826419

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

    PubMed

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

    2009-10-01

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

  16. 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.

  17. 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

  18. Acute synovial fluid eosinophilia associated with delayed pressure urticaria: a role for mast cells?

    PubMed

    Miossec, P; Sullivan, T J; Tharp, M D; Volant, A; Le Goff, P

    1987-04-01

    We report a case of exercise induced joint effusion with synovial fluid (SF) eosinophilia of 9,540/mm3 in a patient with delayed pressure urticaria. The SF eosinophilia was an acute but transient event associated with some evidence of local complement activation. Histologic assessment revealed a normal synovial membrane but with no detectable intact mast cells. These observations suggest that mast cells and eosinophils acting in concert can cause joint inflammation.

  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 IL-15 in rheumatoid arthritis is not influenced by blockade of tumour necrosis factor

    PubMed Central

    Ernestam, Sofia; af Klint, Erik; Catrina, Anca Irinel; Sundberg, Erik; Engström, Marianne; Klareskog, Lars; Ulfgren, Ann-Kristin

    2006-01-01

    Blockade of tumour necrosis factor (TNF) is an effective treatment in rheumatoid arthritis (RA), but both non-responders and partial responders are quite frequent. This suggests that other pro-inflammatory cytokines may be of importance in the pathogenesis of RA and as possible targets for therapy. In this study we investigated the effect of TNF blockade (infliximab) on the synovial expression of IL-15 in RA in relation to different cell types and expression of other cytokines, to elucidate whether or not IL-15 is a possible target for therapy, independently of TNF blockade. Two arthroscopies with multiple biopsies were performed on nine patients with RA and knee-joint synovitis before and after three infusions of infliximab (3 mg/kg). Synovial biopsies were analysed with immunohistochemistry for expression of IL-15, TNF, IL-1α, IL-1ß and IFN-γ, and for the cell surface markers CD3, CD68 and CD163. Stained synovial biopsy sections were evaluated by computerized image analysis. IL-15 expression was detected in all synovial biopsies taken at baseline. After infliximab therapy, the expression of IL-15 was increased in four patients and reduced in five. Synovial expression of IL-15 was not correlated with any CD marker or with the presence of any other cytokine. Synovial cellularity was decreased after 8 to 10 weeks of treatment with a significant reduction of the CD68-positive synovial cells, whereas no significant change was seen in the number of CD3-positive T cells and CD163-expressing macrophages. The number of TNF-producing cells in the synovial tissue at baseline was correlated with a good response to therapy. Thus, in this study the synovial expression of IL-15 in RA was not consistently influenced by TNF blockade, being apparently independent of TNF expression in the synovium. Consequently, we propose that IL-15 should remain as a therapeutic target in RA, regardless of the response to TNF blockade. PMID:16507118

  1. Absolute identification of muramic acid, at trace levels, in human septic synovial fluids in vivo and absence in aseptic fluids.

    PubMed

    Fox, A; Fox, K; Christensson, B; Harrelson, D; Krahmer, M

    1996-09-01

    This is the first report of a study employing the state-of-the-art technique of gas chromatography-tandem mass spectrometry for absolute identification of muramic acid (a marker for peptidoglycan) at trace levels in a human or animal body fluid or tissue. Daughter mass spectra of synovial fluid muramic acid peaks (> or = 30 ng/ml) were identical to those of pure muramic acid. Absolute chemical identification at this level represents a 1,000-fold increase in sensitivity over previous gas chromatography-mass spectrometry identifications. Muramic acid was positively identified in synovial fluids during infection and was eliminated over time but was absent from aseptic fluids.

  2. 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

  3. Influence of electromagnetic fields on the enzyme activity of rheumatoid synovial fluid cells in vitro.

    PubMed

    Mohamed-Ali, H; Kolkenbrock, H; Ulbrich, N; Sörensen, H; Kramer, K D; Merker, H J

    1994-04-01

    Since positive clinical effects have been observed in the treatment of rheumatoid arthritis with electromagnetic fields of weak strength and low frequency range (magnetic field strength: 70 microT; frequency: 1.36-14.44 Hz), an attempt was made to analyse the effects of these electromagnetic fields on enzyme activity in monolayer cultures of rheumatoid synovial fluid cells after single irradiation of the cultures for 24 hours. We only investigated the matrix metalloproteinases (collagenase, gelatinase, proteinase 24.11 and aminopeptidases). It was found that electromagnetic fields of such a weak strength and low frequency range do not generally have a uniform effect on the activity of the different proteinases in vitro. While aminopeptidases do not show any great changes in activity, the peptidases hydrolysing N(2,4)-dinitrophenyl-peptide exhibit a distinct increase in activity in the late phase in culture medium without fetal calf serum. In the presence of fetal calf serum this effect is not observed and enzyme activity is diminished. Our experiments do not show whether such a phase-bound increase in the activity of proteinases in vitro is only one finding in a much broader range of effects of electromagnetic fields, or whether it is a specific effect of weak pulsed magnetic fields of 285 +/- 33 nT on enzyme activity after single irradiation. This question requires further elucidation.

  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. Relevance of synovial fluid chondroitin sulphate as a biomarker to monitor polo pony joints.

    PubMed

    Baccarin, Raquel Y A; Rasera, Luciane; Machado, Thaís S L; Michelacci, Yara M

    2014-01-01

    Osteoarthritis (OA) of the metacarpophalangeal joint is the most common articular disease in polo ponies leading to early retirement. A biomarker that would discriminate between pathological and physiological changes secondary to exercise could be helpful in OA prevention. The aim of this study was to investigate the effects of polo training on synovial fluid biomarkers of inflammation and cartilage turnover in polo ponies of different skill levels. Synovial fluid samples were collected from metacarpophalangeal joints of polo ponies before and during the polo season (320 d). Nucleated cells, soluble protein, prostaglandin E2 (PGE2), glycosaminoglycans (GAG), and urea were measured. The main synovial fluid GAG are chondroitin sulphate (CS, ~25 μg/mL) and hyaluronic acid (HA, ~400 μg/mL). After a polo match, a transitory increase in protein and PGE2, but not CS and HA, occurred (expressed as urea ratio), returning to basal levels in 24 h. During the polo season, the number of synovial fluid nucleated cells was always in the normal range. Increases in protein and HA occurred during the initial 40 to 80 d, returning to basal levels afterwards. In contrast, in polo prospects the concentration of CS steadily increased during the season. Long-term follow-up revealed that the synovial fluid CS was significantly higher in polo ponies that developed joint diseases within 24 months following our study. In conclusion, CS seems to be an early marker of articular cartilage damage.

  6. Raman Spectroscopy of Synovial Fluid as a Tool for Diagnosing Osteoarthritis

    PubMed Central

    Esmonde-White, Karen A.; Mandair, Gurjit S.; Raaii, Farhang; Jacobson, Jon A.; Miller, Bruce S.; Urquhart, Andrew G.; Roessler, Blake J.; Morris, Michael D.

    2009-01-01

    For many years, viscosity has been the primary method used by researchers in rheumatology to assess the physiochemical properties of synovial fluid in both normal and osteoarthritic patients. However, progress has been limited by the lack of methods that provide multiple layers of information, use small sample volumes, and are rapid. In this blinded study, Raman spectroscopy was used to assess the biochemical composition of synovial fluid collected from forty patients with clinical evidence of knee osteoarthritis at the time of elective surgical treatment. Severity of knee osteoarthritis was assessed by a radiologist using Kellgren/Lawrence (K/L) scores from knee joint x-rays, while light microscopy and Raman spectroscopy were used to examine synovial fluid aspirates (2–10 µL), deposited on fused silica slides. We show that Raman bands used to describe protein secondary structure and content can be used to detect changes in synovial fluid from osteoarthritic patients. Several Raman band intensity ratios increased significantly in spectra collected from synovial fluid in patients with radiological evidence of osteoarthritis damage. These ratios can be used to provide a “yes/no” damage assessment. Additionally, two ratios increased with K/L score and showed moderate correlative trends. These studies provide evidence that Raman spectroscopy would be a suitable candidate in the evaluation of joint damage in knee osteoarthritis patients. PMID:19566306

  7. Raman spectroscopy of synovial fluid as a tool for diagnosing osteoarthritis

    NASA Astrophysics Data System (ADS)

    Esmonde-White, Karen A.; Mandair, Gurjit S.; Raaii, Farhang; Jacobson, Jon A.; Miller, Bruce S.; Urquhart, Andrew G.; Roessler, Blake J.; Morris, Michael D.

    2009-05-01

    For many years, viscosity has been the primary method used by researchers in rheumatology to assess the physiochemical properties of synovial fluid in both normal and osteoarthritic patients. However, progress has been limited by the lack of methods that provide multiple layers of information, use small sample volumes, and are rapid. Raman spectroscopy was used to assess the biochemical composition of synovial fluid collected from 40 patients with clinical evidence of knee osteoarthritis (OA) at the time of elective surgical treatment. Severity of knee osteoarthritis was assessed by a radiologist using Kellgren/Lawrence (K/L) scores from knee joint x rays, while light microscopy and Raman spectroscopy were used to examine synovial fluid (SF) aspirates (2 to 10 μL), deposited on fused silica slides. We show that Raman bands used to describe protein secondary structure and content can be used to detect changes in synovial fluid from osteoarthritic patients. Several Raman band intensity ratios increased significantly in spectra collected from synovial fluid in patients with radiological evidence of moderate-to-severe osteoarthritis damage. These ratios can be used to provide a ``yes/no'' damage assessment. These studies provide evidence that Raman spectroscopy would be a suitable candidate in the evaluation of joint damage in knee osteoarthritis patients.

  8. 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

  9. The role of protein content on the steady and oscillatory shear rheology of model synovial fluids.

    PubMed

    Zhang, Z; Barman, S; Christopher, G F

    2014-08-28

    Recent studies have debated the role of protein content on the bulk rheology of synovial fluid; in particular, it has been questioned if proteins aggregate or interact with hyaluronic acid in synovial fluid to enhance bulk rheology, or if observed effects were due to systematic measurement error caused by interfacial rheology, stemming from protein adsorption to the interface. Utilizing several techniques to ensure results reflect only bulk rheology, an examination of the role of bovine serum albumin and γ-globulin on model synovial fluid rheology has been undertaken. When interfacial rheology caused by protein adsorption to the interface is abrogated, the bulk rheology of a model synovial fluid composed of bovine serum albumin, γ-globulin, and hyaluronic acid is found to be dominated solely by the hyaluronic acid over a wide range of shear rates, strains and frequencies. These results show that the previously reported enhanced rheological properties of model synovial fluids are solely due to interfacial rheology and not from any type of protein aggregation/interaction in bulk solution.

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

    PubMed Central

    Sharma, H.; Pigott, R.

    1992-01-01

    The intercellular adhesion molecule-1 (ICAM-1) was found by immunostaining chondrocytes in cartilage from three patients with rheumatoid arthritis. Expression of ICAM-1 was restricted to chondrocytes in areas of erodedcartilage adjacent to the invading synovial tissue. Toluidine blue staining of these areas demonstrated severe depletion of the cartilage extracellular matrix. In areas of undamaged cartilage there was no ICAM-1 expression. Since ICAM-1 is not constitutively expressed on normal human articular cartilage, but could be induced in vitro by exogenous IL-1α, TNFα and IFNγ or by co-culturing cartilage with inflammatory rheumatoid synovium, we conclude that the induction of ICAM-1 on rheumatoid chondrocytes results from the synergistic action of a variety of cytokines produced by the inflammatory cells of the invading pannus. PMID:18475445

  11. Increased synovial expression of nuclear receptors correlates with arthritis protection: a possible novel genetically-regulated homeostatic mechanism

    PubMed Central

    Brenner, Max; Linge, Carl P.; Li, Wentian; Gulko, Pércio S.

    2011-01-01

    Objective To use microarray analyses of gene expression to characterize the synovial molecular pathways regulated by the arthritis regulatory locus Cia25, and how it operates to control disease severity and joint damage. Methods Synovial tissues from DA and DA.ACI(Cia25) rats obtained 21 days post-induction of pristane-induced arthritis were used for RNA extraction and hybridization to Illumina Rat-Ref 12 Beadchips (22,228 genes). A p-value ≤0.01 plus a fold-difference ≥1.5 were considered significant. Results IL-1β (7-fold), IL-6 (67-fold), Ccl2, Cxcl10, Mmp3, Mmp14, and innate immunity genes were expressed in increased levels in DA and in significantly lower levels in congenics. DA.ACI(Cia25) had increased expression of ten nuclear receptors (NR) genes, including those known to interfere with NFκB activity and cytokine expression, such as Lxrα, Pparγ, and Rxrγ. DA.ACI(Cia25) also had increased expression of NR targets suggesting increased NR activity. While the Vdr was not differentially expressed, a Vdr expression signature was detected in congenics, along with up-regulation of mediators of vitamin D synthesis. Conclusions This is the first description of the association between increased synovial levels of NRs and arthritis protection. The expression of NRs was inversely correlated with the expression of key mediators of arthritis suggesting reciprocally opposing effects either via NFκB or at the genomic level in the synovial tissue. We consider that the NR signature may have an important role in maintaining synovial homeostasis and an inflammation-free tissue. These processes are regulated by the Cia25 gene and suggest a new function for this gene. PMID:21702016

  12. 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

  13. Loading-induced changes in synovial fluid affect cartilage metabolism.

    PubMed

    van de Lest, C H; van den Hoogen, B M; van Weeren, P R

    2000-01-01

    The object of this study was to determine whether changes in the synovial fluid (SF) induced by in vivo loading can alter the metabolic activity of chondrocytes in vitro, and, if so, whether insulin-like growth factor-I (IGF-I) is responsible for this effect. Therefore, SF was collected from ponies after a period of box rest and after they had been exercised for a week. Normal, unloaded articular cartilage explants were cultured in 20% solutions of these SFs for 4 days and chondrocyte bioactivity was determined by glycosaminoglycan (GAG) turnover (i.e., the incorporation of 35SO4 into GAG and the release of GAG into the medium). Furthermore, the extent to which the bioactivity is IGF-I-dependent was determined in a cartilage explant culture in 20% SF, in the presence and absence of anti-IGF-I antibodies. In explants cultured in post-exercise SF, GAG synthesis was enhanced and GAG release was diminished when compared to cultures in pre-exercise SF. SF analysis showed that IGF-I and IGFBP-3 levels were increased in post-exercise SF. There was a positive correlation between IGF-I levels and proteoglycan synthesis, but no correlation between IGF-I levels and proteoglycan release. Addition of anti-IGF-I antibodies significantly inhibited stimulation of proteoglycan synthesis in explants cultured in SF with 40%. However, there was no difference in inhibition of proteoglycan synthesis between pre- and post-exercise SF which indicated that the relative contribution of IGF-I in the stimulating effect of SF did not change. Proteoglycan release was not influenced by the presence of anti-IGF-I antibodies. It is concluded that chondrocyte metabolic activity is at least partially regulated by changes in the SF induced by in vivo loading. Exercise altered the SF in a way that it had a favourable effect on cartilage PG content by enhancing the PG synthesis and reducing the PG breakdown. IGF-I is an important contributor to the overall stimulating effect of SF on cartilage

  14. 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.

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

    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.

  16. Reverse Transcriptase-PCR Analysis of Bacterial rRNA for Detection and Characterization of Bacterial Species in Arthritis Synovial Tissue

    PubMed Central

    Kempsell, Karen E.; Cox, Charles J.; Hurle, Michael; Wong, Anthony; Wilkie, Scott; Zanders, Edward D.; Gaston, J. S. Hill; Crowe, J. Scott

    2000-01-01

    Onset of rheumatoid arthritis (RA) is widely believed to be preceded by exposure to some environmental trigger such as bacterial infectious agents. The influence of bacteria on RA disease onset or pathology has to date been controversial, due to inconsistencies between groups in the report of bacterial species isolated from RA disease tissue. Using a modified technique of reverse transcriptase-PCR amplification, we have detected bacterial rRNA in the synovial tissue of late-stage RA and non-RA arthritis controls. This may be suggestive of the presence of live bacteria. Sequencing of cloned complementary rDNA (crDNA) products revealed a number of bacterial sequences in joint tissue from each patient, and from these analyses a comprehensive profile of the organisms present was compiled. This revealed a number of different organisms in each patient, some of which are common to both RA and non-RA controls and are probably opportunistic colonizers of previously diseased tissue and others which are unique species. These latter organisms may be candidates for a specific role in disease pathology and require further investigation to exclude them as causative agents in the complex bacterial millieu. In addition, many of the detected bacterial species have not been identified previously from synovial tissue or fluid from arthritis patients. These may not be easily cultivable, since they were not revealed in previous studies using conventional in vitro bacterial culture methods. In situ hybridization analyses have revealed the joint-associated bacterial rRNA to be both intra- and extracellular. The role of viable bacteria or their nucleic acids as triggers in disease onset or pathology in either RA or non-RA arthritis controls is unclear and requires further investigation. PMID:10992514

  17. Novel insights in the regulation of CCL18 secretion by monocytes and dendritic cells via cytokines, Toll-like receptors and rheumatoid synovial fluid

    PubMed Central

    van Lieshout, Antoine WT; van der Voort, Robbert; le Blanc, Linda MP; Roelofs, Mieke F; Schreurs, B Willem; van Riel, Piet LCM; Adema, Gosse J; Radstake, Timothy RDJ

    2006-01-01

    Background The T cell attracting chemokine CCL18 is produced by antigen presenting cells and a role for CCL18 has been suggested in the pathogenesis of a variety of diseases. Rheumatoid arthritis (RA) is one of these conditions, in which abundant CCL18 production is present. Although Th2 cytokines and IL-10 are known to have an effect on CCL18 production, there are several gaps in our knowledge regarding the exact regulation of CCL18 secretion, both in general and in RA. In this study we provide new insights in the regulation of CCL18 secretion by monocytes and dendritic cells. Results In contrast to a large panel of pro-inflammatory stimuli (IL-1β, TNF-α, IL-10, IL-13, IL-15, IL-17, IL-18, IFN-γ), T cell mimicking molecules (RANKL, CD40L) or TLR driven maturation, the anti-inflammatory IL-10 strongly stimulated DC to secrete CCL18. On freshly isolated monocytes, CCL18 secretion was induced by IL-4 and IL-13, in strong synergy with IL-10. This synergistic effect could already be observed after only 24 hours, indicating that not only macrophages and dendritic cells, but also monocytes secrete CCL18 under these stimulatory conditions. A high CCL18 expression was detected in RA synovial tissue and incubation of monocytes with synovial fluid from RA patients clearly enhanced the effects of IL-4, IL-13 and IL-10. Surprisingly, the effect of synovial fluid was not driven by IL-10 of IL-13, suggesting the presence of another CCL18 inducing factor in synovial fluid. Conclusion In summary, IL-10 synergistically induces CCL18 secretion in combination with IL-4 of IL-13 on monocytes and monocyte derived cells. The effects of IL-14, IL-13 and IL-10 are strongly enhanced by synovial fluid. This synergy may contribute to the high CCL18 expression in RA. PMID:16984635

  18. The prevalence of monosodium urate and calcium pyrophosphate crystals in synovial fluid from wrist and finger joints.

    PubMed

    Galozzi, Paola; Oliviero, Francesca; Frallonardo, Paola; Favero, Marta; Hoxha, Ariela; Scanu, Anna; Lorenzin, Mariagrazia; Ortolan, Augusta; Punzi, Leonardo; Ramonda, Roberta

    2016-03-01

    The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients' medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP-crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10% in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.

  19. A role for plasma kallikrein-kinin system activation in the synovial recruitment of endothelial progenitor cells in arthritis

    PubMed Central

    Dai, Jihong; Agelan, Alexis; Yang, Aizhen; Zuluaga, Viviana; Sexton, Daniel; Colman, Robert W.; Wu, Yi

    2012-01-01

    Objective To examine whether the activation of plasma kallikrein-kinin system (KKS) mediates synovial recruitment of endothelial progenitor cells (EPCs) in arthritis. Methods EPCs were isolated from Lewis rat bone marrow and characterized by the expression of progenitor cell lineage markers and functional property. EPCs were intravenously injected into Lewis rats bearing arthritis, their recruitment and formation of de novo blood vessels in inflamed synovium were evaluated. The role of plasma KKS was examined using a plasma kallikrein inhibitor EPI-KAL2 and an anti-kallikrein antibody 13G11. Transendothelial migration (TEM) assay was used to determine the role of bradykinin and its receptor in EPC mobilization. Results Lewis rat EPCs exhibited strong capacities to form tubes and vacuoles, and expressed higher level of bradykinin type 2 receptor (B2R) and progenitor cell markers CD34 and Sca-1. In Lewis rats bearing arthritis, EPCs were recruited into inflamed synovium at acute phase and formed de novo blood vessels. Inhibition of plasma kallikrein by EPI-KAL2 and 13G11 significantly suppressed synovial recruitment of EPCs and hyperproliferation of synovial cells. Bradykinin concentration-dependently stimulated TEM of EPCs, which was mediated by B2R, as the knockdown of B2R by silencing RNA completely blocked bradykinin-stimulated TEM. Moreover, bradykinin selectively upregulated the expression of homing receptor C-X-C chemokine receptor type 4 (CXCR-4) in EPCs. Conclusion These observations demonstrate a novel role for plasma KKS activation in the synovial recruitment of EPCs in arthritis, acting via kallirein activation and B2R-dependent mechanisms. B2R might be involved in the mobilization of EPCs via upregulation of CXCR-4. PMID:22739815

  20. 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.

  1. THE CATION CHANNEL TRPV2 IS A NEW SUPPRESSOR OF ARTHRITIS SEVERITY, JOINT DAMAGE AND SYNOVIAL FIBROBLAST INVASION

    PubMed Central

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

    2015-01-01

    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

  2. Synovial fluid response to extensional flow: effects of dilution and intermolecular interactions.

    PubMed

    Haward, Simon J

    2014-01-01

    In this study, a microfluidic cross-slot device is used to examine the extensional flow response of diluted porcine synovial fluid (PSF) samples using flow-induced birefringence (FIB) measurements. The PSF sample is diluted to 10× 20× and 30× its original mass in a phosphate-buffered saline and its FIB response measured as a function of the strain rate at the stagnation point of the cross-slots. Equivalent experiments are also carried out using trypsin-treated PSF (t-PSF) in which the protein content is digested away using an enzyme. The results show that, at the synovial fluid concentrations tested, the protein content plays a negligible role in either the fluid's bulk shear or extensional flow behaviour. This helps support the validity of the analysis of synovial fluid HA content, either by microfluidic or by other techniques where the synovial fluid is first diluted, and suggests that the HA and protein content in synovial fluid must be higher than a certain minimum threshold concentration before HA-protein or protein-protein interactions become significant. However a systematic shift in the FIB response as the PSF and t-PSF samples are progressively diluted indicates that HA-HA interactions remain significant at the concentrations tested. These interactions influence FIB-derived macromolecular parameters such as the relaxation time and the molecular weight distribution and therefore must be minimized for the best validity of this method as an analytical technique, in which non-interaction between molecules is assumed.

  3. 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...

  4. 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.

  5. Detection of Mycobacterium tuberculosis Group Organisms in Human and Mouse Joint Tissue by Reverse Transcriptase PCR: Prevalence in Diseased Synovial Tissue Suggests Lack of Specific Association with Rheumatoid Arthritis

    PubMed Central

    Kempsell, Karen E.; Cox, Charles J.; McColm, Andrew A.; Bagshaw, Julie A.; Reece, Richard; Veale, Douglas J.; Emery, Paul; Isaacs, John D.; Gaston, J. S. Hill; Crowe, J. Scott

    2001-01-01

    Infection with mycobacterial species, including Mycobacterium tuberculosis, has long been implicated in the etiopathology of rheumatoid arthritis (RA) on the basis of clinical and pathological similarities between tuberculosis and RA. Despite evidence of immune responses to mycobacterial antigens in RA patient synovial fluid, cross-reactivity between these and host joint antigens, and the presence of M. tuberculosis protein antigen in RA synovial fluid, a definite causal association with RA has not been shown. Previous studies from our laboratory using reverse transcriptase PCR (RT-PCR) of bacterial rRNAs have shown RA synovium to be colonized by a diverse range of bacteria, most of commensal origin. However, M. tuberculosis group organism (MTG) RNA sequences were found in one RA patient tissue. Since this was considered of sufficient interest to warrant further investigation, we devised a M. tuberculosis-specific nested RT-PCR test which could be used for detection of MTG in a mixed pool of bacterial crDNAs. This test was used to investigate the distribution of MTG in RA synovial tissue and also non-RA arthritis and healthy control tissues and was also used to examine the tissue distribution of MTG in an acute and chronic model of M. tuberculosis infection in the BALB/c mouse. MTG sequences were found in a high proportion of RA patient synovial tissues but also in non-RA arthritis control tissues at lower frequency. This likely reflects trafficking of persistent M. bovis BCG to inflamed joint tissue, irrespective of cause. MTG were not found in healthy synovial tissue or the tissue of patients with undifferentiated arthritis. In both the acute and chronic models of infection in BALB/c mice, M. tuberculosis was also found to have trafficked to joint tissues, however, no signs of inflammation, arthritis, or pathology associated with M. tuberculosis infection was seen. These combined results would argue against a specific causal role of MTG in RA-like arthritis

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

    PubMed

    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.

  7. Characteristics of synovial fluid required for optimization of lubrication fluid for biotribological experiments.

    PubMed

    Galandáková, Adéla; Ulrichová, Jitka; Langová, Kateřina; Hanáková, Adéla; Vrbka, Martin; Hartl, Martin; Gallo, Jiri

    2016-04-18

    Wear testing of total joint replacement (TJR) is mandatory in preclinical testing before implantation of TJR into the human body. Testing is governed by current international standards that recommend bovine serum (BS) as a lubricating fluid to replace synovial fluid (SF). Recently, the use of BS has been criticized because of differences in content, fluid characteristics, and nonhuman origin. As a result, a more realistic lubricant mimicking SF is needed. To define SF composition, we analyzed SF obtained during revisions of total hip and knee arthroplasties and compared it with SF obtained during primary arthroplasties and from patients without TJR. Samples were acquired from 152 patients. We found that the median total protein concentration for all SF was 36.8 mg/mL, which is significantly higher than concentrations currently recommended by the ISO standards. The γ-globulin concentration was significantly higher and the phospholipid concentration significantly lower in patients with revision of TJR compared with patients without TJR. No significant difference was found in hyaluronic acid concentration and viscosity among the groups. Our results support the need to improve the definition of a more clinically relevant wear testing lubricant in the ISO standards. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  8. 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

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

    PubMed Central

    Bauer, Gregor; Willburger, Martin; Sinn, Katharina; Alasti, Farideh; Plasenzotti, Roberto; Shvets, Tetyana; Niederreiter, Birgit; Aschauer, Constantin; Steiner, Guenter; Podesser, Bruno K.; Smolen, Josef S.; Redlich, Kurt

    2016-01-01

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

  10. Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis.

    PubMed

    Park, Cheol; Moon, Dong-Oh; Choi, Il-Whan; Choi, Byung Tae; Nam, Taek-Jeong; Rhu, Chung-Ho; Kwon, Taeg Kyu; Lee, Won Ho; Kim, Gi-Young; Choi, Yung Hyun

    2007-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of anti-apoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumin-induced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E(2) synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.

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

    PubMed

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

    2012-06-01

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

  12. 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.

  13. Sporotrichosis arthritis: clinical features in seven patients.

    PubMed

    Crout, J E; Brewer, N S; Tompkins, R B

    1977-03-01

    A review of the clinical features of seven patients with sporotrichosis arthritis showed that six had joint infection without previous skin or lung involvement and that one with myelofibrosis had joint and skin infection. The average time from onset of joint symptoms to diagnosis was 25 months, resulting in joint damage that required arthrodesis in four patients. Tissue from open synovial biopsy was superior to synovial fluid for obtaining a positive culture; concomitant synovial fluid and synovial tissue cultures were superior to either one alone. Granulomatous inflammation was seen in synovial tissue in six patients biopsied. Amphotericin B with surgical debridement of the affected joint was successful treatment in four patients. Although an uncommon cause of joint disease, sporotrichosis arthritis may go unrecognized and mimic other forms of arthritis, resulting in irreparable damage in an otherwise curable form of arthritis.

  14. 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.

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:27877822

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

    PubMed Central

    Zhao, Chenqi; Moreno-Nieves, Uriel; Di Battista, John A.; Fernandes, Maria J.; Touaibia, Mohamed; Bourgoin, Sylvain G.

    2015-01-01

    Emerging evidence suggests a role for sphingosine-1-phosphate (S1P) in various aspects of rheumatoid arthritis (RA) pathogenesis. In this study we compared the effect of chemical hypoxia induced by cobalt chloride (CoCl2) on the expression of S1P metabolic enzymes and cytokine/chemokine secretion in normal fibroblast-like synoviocytes (FLS) and RAFLS. RAFLS incubated with CoCl2, but not S1P, produced less IL-8 and MCP-1 than normal FLS. Furthermore, incubation with the S1P2 and S1P3 receptor antagonists, JTE-013 and CAY10444, reduced CoCl2-mediated chemokine production in normal FLS but not in RAFLS. RAFLS showed lower levels of intracellular S1P and enhanced mRNA expression of S1P phosphatase 1 (SGPP1) and S1P lyase (SPL), the enzymes that are involved in intracellular S1P degradation, when compared to normal FLS. Incubation with CoCl2 decreased SGPP1 mRNA and protein and SPL mRNA as well. Inhibition of SPL enhanced CoCl2-mediated cytokine/chemokine release and restored autocrine activation of S1P2 and S1P3 receptors in RAFLS. The results suggest that the sphingolipid pathway regulating the intracellular levels of S1P is dysregulated in RAFLS and has a significant impact on cell autocrine activation by S1P. Altered sphingolipid metabolism in FLS from patients with advanced RA raises the issue of synovial cell burnout due to chronic inflammation. PMID:26556954

  18. Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues

    PubMed Central

    Shahrara, Shiva; Castro-Rueda, Hernan P; Haines, G Kenneth; Koch, Alisa E

    2007-01-01

    The focal adhesion kinase (FAK) family kinases, including FAK and proline-rich kinase 2 (Pyk)2, are the predominant mediators of integrin αvβ3 signaling events that play an important role in cell adhesion, osteoclast pathology, and angiogenesis, all processes important in rheumatoid arthritis (RA). Using immunohistochemical and western blot analysis, we studied the distribution of phospho (p)FAK, pPyk2, pSrc, pPaxillin and pPLCγ in the synovial tissue (ST) from patients with RA, osteoarthritis (OA) and normal donors (NDs) as well as in RA ST fibroblasts and peripheral blood differentiated macrophages (PB MΦs) treated with tumor necrosis factor-α (TNFα) or interleukin-1β (IL1β). RA and OA STs showed a greater percentage of pFAK on lining cells and MΦs compared with ND ST. RA ST fibroblasts expressed pFAK at baseline, which increased with TNFα or IL1β stimulation. Pyk2 and Src were phosphorylated more on RA versus OA and ND lining cells and MΦs. pPyk2 was expressed on RA ST fibrobasts but not in MΦs at baseline, however it was upregulated upon TNFα or IL1β activation in both cell types. pSrc was expressed in RA ST fibroblasts and MΦs at baseline and was further increased by TNFα or IL1β stimulation. pPaxillin and pPLCγ were upregulated in RA versus OA and ND lining cells and sublining MΦs. Activation of the FAK family signaling cascade on RA and OA lining cells may be responsible for cell adhesion and migration into the diseased STs. Therapies targeting this novel signaling pathway may be beneficial in RA. PMID:17963503

  19. MicroRNAs interfere with DNA methylation in rheumatoid arthritis synovial fibroblasts

    PubMed Central

    Gaur, Niharika; Karouzakis, Emmanuel; Glück, Selene; Bagdonas, Edvardas; Jüngel, Astrid; Michel, Beat A; Gay, Renate E; Gay, Steffen; Frank-Bertoncelj, Mojca; Neidhart, Michel

    2016-01-01

    Background The DNA of rheumatoid arthritis synovial fibroblasts (RASF) is globally hypomethylated; this contributes to an aggressive behaviour. In an attempt to remethylate these cells, we supplemented with methyl donors. We investigated the possible interference of microRNAs (miRs). Material and methods RASF were treated with L-methionine or betaine. Transcripts of de novo methyltransferases (DNMTs) and miRs were measured by real-time PCR, and a transcription PCR array was performed. Levels of homocysteine, matrix metalloproteinase-1 (MMP-1) and global DNA methylation were determined. Transfection with lipofectamine was performed with specific pre-miRs and anti-miRs, such as miR29 and let7f. Results L-methionine was more efficient to increase DNA methylation than betaine. This was associated with a reduced expression of DNMT3A mRNA in betaine-treated RASF. Betaine increases the expression of miR29 in RASF which targets DNMT3A, thereby limiting the remethylation process. Nevertheless, betaine inhibited the expression of multiple transcription factors, decreased the release of MMP-1, biosynthesis of homocysteine and cell migration. Conclusion Alterations in cellular miRs profiles, in particular the upregulation of miR29, which targets DNMT3A, may limit the efficiency of betaine if it is used as DNA remethylating agent. However, L-methionine also has similar impact on miR29 expression. On the other hand, betaine has multiple other beneficial effects on the activated phenotype of RASF; it is not excluded that the effect of betaine on DNMT3A is, at least in part, indirect. Clinical trials with betaine could be promising. PMID:27843576

  20. Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthritis patients

    PubMed Central

    Lindberg, Johan; af Klint, Erik; Catrina, Anca Irinel; Nilsson, Peter; Klareskog, Lars; Ulfgren, Ann-Kristin; Lundeberg, Joakim

    2006-01-01

    and CXCL14). Subsequent Gene Ontology analysis revealed that several 'themes' were significantly over-represented that are known to be affected by anti-TNF treatment in inflammatory tissue; for example, immune response (GO:0006955), cell communication (GO:0007154), signal transduction (GO:0007165) and chemotaxis (GO:0006935). No genes reached statistical significance in the moderately responding or nonresponding groups. In conclusion, this pilot study suggests that further investigation is warranted on the usefulness of gene expression profiling of synovial tissue to predict and monitor the outcome of rheumatoid arthritis therapies. PMID:17134501

  1. Ulnar neuropathy caused by a widespread synovial cyst of the elbow joint in a patient with rheumatoid arthritis.

    PubMed

    Scholz, Christoph; Gierthmuehlen, Mortimer; Egger, Karl; Hauschild, Oliver; van Velthoven-Wurster, V

    2014-11-01

    A 53-year-old man with rheumatoid arthritis presented with radiating pain, numbness, and diminished motor strength in the right hand according to the ulnar nerve functions. Magnetic resonance imaging and peripheral nerve ultrasound revealed a widespread cystic lesion descending from the elbow joint along the ulnar nerve over a length of 8 cm. After relapse under a therapeutic attempt with antirheumatic drugs, neurosurgical exploration was done using peripheral nerve ultrasound. A synovial cyst of the elbow was extirpated as a whole with subsequent anterior synovectomy. The postoperative course was uneventful with gradual recovery of function.

  2. Antioxidant capacity of synovial fluid in the temporomandibular joint correlated with radiological morphology of temporomandibular disorders.

    PubMed

    Ishimaru, Kyoko; Ohba, Seigo; Yoshimura, Hitoshi; Matsuda, Shinpei; Ishimaru, Jun-Ichi; Sano, Kazuo

    2015-02-01

    We investigated the correlation between the antioxidant capacity of synovial fluid and radiological findings of intra-articular structures in patients with disorders of the temporomandibular joint (TMJ). We recruited 21 patients (9 men and 12 women, aged 18-84 years of age) with such disorders, excluding myofascial pain and dysfunction syndrome, or other muscular disorders. The clinical variables recorded included age, sex, interincisal distance, and visual analogue pain scores (VAS). Radiological findings were obtained from diagnostic arthrogram and cone-beam computed tomography (CT). The antioxidant capacity of the synovial fluid was measured by chemiluminescence. Eleven patients were radiologically diagnosed with closed lock, and the remaining 10 with no closed lock. An anchored intra-articular disc was most often seen on cone-beam CT (n=19) followed by perforated disc (n=7), osteoarthrosis (n=7), and anterior disc displacement without reduction (n=5). Although there were no significant differences between antioxidant capacity and age, sex, VAS, or any findings on cone-beam CT, antioxidant capacity was significantly decreased in the patients with closed lock compared with those who did not have closed lock (p=0.02). The results suggest an association between the oxidative stress of the synovial fluid and closed-lock in disorders of the TMJ.

  3. Enantiospecific pharmacokinetics of ketoprofen in plasma and synovial fluid of horses with acute synovitis.

    PubMed

    Verde, C R; Simpson, M I; Frigoli, A; Landoni, M F

    2001-06-01

    Pharmacokinetic parameters were established for enantiomers of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (KTP) administered as the racemic mixture at a dose of 2.2 mg/kg and as separate enantiomers, each at a dose of 1.1 mg/kg to a group of six horses (five mares and one gelding). A four-period cross-over study in a LPS-induced model of acute synovitis was used. After administration of the racemic mixture S(+)KTP was the predominant enantiomer in plasma as well as in synovial fluid. Unidirectional inversion of R(-) to S(+)KTP was demonstrated but the inversion was less marked than previously reported. It is suggested that this reduction could be because of the influence of the inflammatory reaction on hepatic metabolism. The disposition of KTP enantiomers after administration of the racemic mixture was similar to those observed after administration of S(+) and R(-)KTP. The S(+) and R(-)KTP concentrations in synovial fluid were low and short lasting. After administration of R(-)KTP significant concentrations of the optical antipode were detected in synovial fluid.

  4. Penetration of Daptomycin into Bone and Synovial Fluid in Joint Replacement

    PubMed Central

    Montange, D.; Berthier, F.; Leclerc, G.; Serre, A.; Jeunet, L.; Berard, M.; Muret, P.; Vettoretti, L.; Leroy, J.; Hoen, B.

    2014-01-01

    Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array–high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections. PMID:24798278

  5. Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

    PubMed Central

    Wu, Chia-Lung; Kimmerling, Kelly A.; Little, Dianne; Guilak, Farshid

    2017-01-01

    High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity. PMID:28317846

  6. The effect of sodium hyaluronate treating knee osteoarthritis on synovial fluid interleukin -1β and clinical treatment mechanism.

    PubMed

    Yang, Libin; Zhang, Jun; Wang, Guodong

    2015-01-01

    In order to explore the influence of sodium hyaluronate on knee osteoarthritis (KOA) patients synovial fluid interleukin -1β (IL-1β) and analyze its clinical mechanism, this study analyzed 40 cases of KOA patients in our hospital's orthopaedic department, randomly divided them into two groups: Sodium hyaluronate group (group A) and normal saline group (group B), each consists 20 patients. Besides, we selected another 20 patients as normal control group. Group A treated knee joint cavity by injecting sodium hyaluronate, and group B injected knee joint cavity in equal amount of normal saline, once a week for five weeks. Collect respectively knee joint synovial fluid in patients of group A and group B before treatment and after five weeks of treatment, detect the content of knee joint synovial fluid IL-1βin of all the three groups by using enzyme linked immunosorbent assay (ELISA). We can conclude that (1) IL-1β content of knee joint synovial fluid in KOA patients before treatment was significantly higher than healthy people; (2) IL-1β content of group A knee joint synovial fluid after treatment was significantly reduced than before treatment, there was no significant difference for group BIL-1β content before and after treatment; (3) there was no significant difference between group A knee joint synovial fluid IL-1β content after treatment and healthy people. Thus it can be proved that content of IL-1β in knee joint synovial fluid KOA patients is higher than healthy people; sodium hyaluronate can reduce the content of IL-1β in synovial joints and can be effective in the treatment of knee osteoarthritis.

  7. The effect of depth of centrifuged synovial fluid on leukocyte esterase test for periprosthetic joint infection.

    PubMed

    Ruangsomboon, Pakpoom; Chinprasertsuk, Sriprapa; Khejonnit, Varanya; Chareancholvanich, Keerati

    2017-03-17

    Centrifugation of aspirated synovial fluid before leukocytes esterase (LE) testing for diagnosing periprosthetic joint infection (PJI) may make blood tinged specimens interpretable. We aimed to establish the proper sampling depth of centrifuged specimens for LE testing as one diagnostic criterion and also AS-D chloroacetate esterase (CAE) staining testing as an adjunctive tool. A definite PJI knee joint group and an aseptic primary total knee arthroplasty control group were studied quasi-experimentally (N = 46). At 2000 g for 15 minutes, 3 ml of synovial fluid was centrifuged. LE strip testing and median synovial WBC count were performed at 2, 4, and 6 mm depths. CAE staining test characterized LE particles. ROC curve, area under the curve, and significant differences were determined. The proper predictive depth to diagnose PJI was sought by forward stepwise logistic regression. All fresh blood-tinged specimens had uncertain interpretations. Centrifugation increased interpretability (55% to 100%). ROC curve and area under the curve at 2, 4, and 6 mm depths were 0.822, 0.804, and 0.786, respectively. The cut point of ++ to diagnose PJI was statistically significant (p < 0.05) at all depths. P-values of forward stepwise logistic regression at 2, 4, and 6 mm were 0.001, 0.752, and 0.756, respectively. CAE staining confirmed extracellular LE release by polymorphonuclear neutrophils (PMN). A specimen at < 2 mm from the surface of centrifuged synovial fluid at a grading of ++ or more for PJI diagnosis is proper for LE testing. CAE staining testing adjunctively characterizes LE particles and cell morphology. This article is protected by copyright. All rights reserved.

  8. AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts

    PubMed Central

    Kato, Masaru; Ospelt, Caroline; Kolling, Christoph; Shimizu, Tomohiro; Kono, Michihito; Yasuda, Shinsuke; Michel, Beat A.; Gay, Renate E.; Gay, Steffen

    2016-01-01

    Valosin containing protein (p97) is a chaperone implicated in a large number of biological processes including endoplasmic reticulum (ER)-associated protein degradation and autophagy. Silencing of p97 in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) increased the amount of polyubiquitinated proteins, whereas silencing of its interaction partner histone deacetylase 6 (HDAC6) had no effect. Furthermore, silencing of p97 in RASFs increased not only rates of apoptotic cell death induced by TRAIL but also induced an autophagy-associated cell death during ER stress that was accompanied by the formation of polyubiquitinated protein aggregates and large vacuoles. Finally, we demonstrated an anti-arthritic effect of siRNAs targeting p97 in collagen-induced arthritis in rats. Our data indicate that p97 may be a new potential target in the treatment of RA. PMID:27623077

  9. 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

  10. Epigenome analysis reveals TBX5 as a novel transcription factor involved in the activation of rheumatoid arthritis synovial fibroblasts.

    PubMed

    Karouzakis, Emmanuel; Trenkmann, Michelle; Gay, Renate E; Michel, Beat A; Gay, Steffen; Neidhart, Michel

    2014-11-15

    In this study, we analyzed the methylation status of human promoters in rheumatoid arthritis synovial fibroblasts (RASF). Differentially methylated genes between RASF and osteoarthritis synovial fibroblasts (OASF) were identified by methylated DNA immunoprecipitation and hybridization to human promoter tiling arrays. The methylation status was confirmed by pyrosequencing. Gene and protein expression of differentially methylated genes was evaluated with real-time PCR, Western blot, and immunohistochemistry. Chromatin immunoprecipitation was used to measure the gene promoter-associated acetylation and methylation of histones. Transcription factor-specific targets were identified with microarray and luciferase assays. We found that the transcription factor T-box transcription factor 5 (TBX5) was less methylated in rheumatoid arthritis (RA) synovium and RASF than in osteoarthritis (OA) samples. Demethylation of the TBX5 promoter in RASF and RA synovium was accompanied by higher TBX5 expression than in OASF and OA synovium. In RA synovium, TBX5 expression was primarily localized to the synovial lining. In addition, the TBX5 locus was enriched in activating chromatin marks, such as histone 4 lysine 4 trimethylation and histone acetylation, in RASF. In our functional studies, we observed that 790 genes were differentially expressed by 2-6-fold after overexpression of TBX5 in OASF. Bioinformatic analysis of these genes revealed that the chemokines IL-8, CXCL12, and CCL20 were common targets of TBX5 in OASF. Taken together, our data show that TBX5 is a novel inducer of important chemokines in RASF. Thus, we conclude that RASF contribute to the inflammatory processes operating in the pathogenesis of RA via epigenetic control of TBX5.

  11. 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

  12. Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells.

    PubMed

    Bertram, Karri L; Banderali, Umberto; Tailor, Pankaj; Krawetz, Roman J

    2016-01-01

    Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.

  13. The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity

    PubMed Central

    Zhu, Li; Wang, Huaizhou; Wu, Yu; He, Zhengwen

    2017-01-01

    Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n = 20) were significantly higher than those in OA patients (n = 16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis. PMID:28255205

  14. IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion.

    PubMed

    Lubberts, E; Joosten, L A; Chabaud, M; van Den Bersselaar, L; Oppers, B; Coenen-De Roo, C J; Richards, C D; Miossec, P; van Den Berg, W B

    2000-06-01

    Bone destruction is the most difficult target in the treatment of rheumatoid arthritis (RA). Here, we report that local overexpression of IL-4, introduced by a recombinant human type 5 adenovirus vector (Ad5E1mIL-4) prevents joint damage and bone erosion in the knees of mice with collagen arthritis (CIA). No difference was noted in the course of CIA in the injected knee joints between Ad5E1mIL-4 and the control vector, but radiographic analysis revealed impressive reduction of joint erosion and more compact bone structure in the Ad5E1mIL-4 group. Although severe inflammation persisted in treated mice, Ad5E1mIL-4 prevented bone erosion and diminished tartrate-resistant acid phosphatase (TRAP) activity, indicating that local IL-4 inhibits the formation of osteoclast-like cells. Messenger RNA levels of IL-17, IL-12, and cathepsin K in the synovial tissue were suppressed, as were IL-6 and IL-12 protein production. Osteoprotegerin ligand (OPGL) expression was markedly suppressed by local IL-4, but no loss of OPG expression was noted with Ad5E1mIL-4 treatment. Finally, in in vitro studies, bone samples of patients with arthritis revealed consistent suppression by IL-4 of type I collagen breakdown. IL-4 also enhanced synthesis of type I procollagen, suggesting that it promoted tissue repair. These findings may have significant implications for the prevention of bone erosion in arthritis.

  15. The use of native fluorescence analysis of synovial fluid in the diagnosis of medial compartment disease in medium- and large-breed dogs.

    PubMed

    Bilská, Kamila; Šteffeková, Zuzana; Birková, Anna; Mareková, Mária; Ledecký, Valent; Hluchý, Marián; Kisková, Terézia

    2016-05-01

    We assumed that proteins are most likely responsible for synovial fluid fluorescence and that changes detected in fluorescence intensity are most likely the result of changes in the concentration of fluorescent proteins. Synchronous fluorescent matrices from synovial fluid samples were measured in the excitation wavelength range of 200-350 nm using a luminescence spectrophotometer. The synchronous matrix of synovial fluid consists of 2 dominant fluorescent centers (F1 and F2) in the ultraviolet region. The fluorescence intensities of both centers were significantly higher in pathological samples, with p = 0.001 (a 59% increase of the median value) for the F1 center and p = 0.002 (a 52% increase of the median value) for the F2 center. Receiver operating characteristic analysis confirmed that synovial fluid autofluorescence is a significant predictor of medial compartment disease in dogs, with the area under the curve at 0.776 (F1) and 0.778 (F2). We did not detect any differences in the autofluorescence of synovial fluid between male and female, or any breed-based changes. No position changes of fluorescent centers were recorded in the synovial fluid in diseased dogs compared with healthy dogs. The synovial fluid metabolic fingerprint of canine patients with medial compartment disease differed from that of healthy dogs. Our study demonstrated the feasibility of synovial fluid fingerprinting to identify disease-specific profiles of synovial fluid metabolites.

  16. Characterization of hyaluronic acid and synovial fluid in stagnation point elongational flow.

    PubMed

    Haward, Simon J

    2014-03-01

    Hyaluronic acid (HA) is an important biomacromolecule, which fulfils a number of vital physiological functions (especially in the joint synovial fluid) and also has consumer and pharmaceutical applications. HA solution properties have already been quite thoroughly characterized in response to steady shear flows but are less well understood in highly deforming extensional flows. In this study, flow-induced birefringence measurements are made as a function of the strain rate in planar elongational flow at the stagnation point of a cross-slot device using HA solutions of a range of molecular weights (0.9×10(6) g mol(-1)≤Mw≤4.8×10(6) g mol(-1)) and at dilute concentrations. The results provide macromolecular relaxation times, molecular weight distributions and the extensional viscosities and Trouton ratios of the fluids. The HA relaxation time is found to vary as τ∼Mw1.8, which is consistent with a partially solvated, expanded coil. An intrinsic Trouton ratio is defined, which varies as [Tr]∼Mw2. The measurement of birefringence with strain rate is shown to be highly sensitive to the molecular weight distribution and can resolve subtle changes due to macromolecular degradation and the presence of fracture products. Mechanical degradation experiments in the cross-slots indicate midchain scission of HA macromolecules, strongly suggesting near full extension of the high-molecular weight fraction in the stagnation point extensional flow field. Taken together the results suggest a possible method for analysis of the HA in synovial fluid, and this concept is tested using synovial fluid obtained from porcine tarsal joint.

  17. Tenidap decreases IL-8 and monocyte chemotactic peptide-1 (MCP-1) mRNA expression in the synovial tissue of rabbits with antigen arthritis and in cultured synovial cells

    PubMed Central

    Palacios, I; Lopez-Armada, M J; Hernandez, P; Sanchez-Pernaute, O; Gutierrez, S; Miguelez, R; Martinez, J; Egido, J; Herrero-Beaumont, G

    1998-01-01

    Since IL-8 and MCP-1 are chemoattractant proteins that participate in the recruitment of inflammatory cells into the arthritic joint, we examined the effects of tenidap, a new anti-inflammatory drug of the oxindole family, on IL-8 and MCP-1 expression in the joints of rabbits with acute antigen arthritis. The model was induced by injecting 5 mg/ml ovalbumin into the knees of 20 preimmunized rabbits. Animals were randomized into two groups: treated with tenidap (15 mg/kg per 12 h), or untreated. The effect of tenidap treatment was evaluated on chemokine production in synovial membranes of rabbits with arthritis and in cultured monocytic and synovial cells (SC). By immunoperoxidase staining, chemokines were localized in the synovial tissue. Chemokine messenger RNA levels in the synovial membranes and in cultured cells were analysed by reverse transcription-polymerase chain reaction (RT-PCR). At the end of the study, tenidap significantly reduced neutrophil infiltration into the joint cavity (27 ± 4 × 106 cells/ml versus 45 ± 6 × 106 cells/ml in untreated; P < 0.05), and synovial effusion (134 ± 15 μl versus 236 ± 19 μl in untreated; P < 0.005). Untreated rabbits showed synovial membrane up-regulation in mRNA expression of IL-8 and MCP-1 (11- and seven-fold versus healthy rabbits, respectively) that was markedly decreased by tenidap (two- and three-fold versus healthy rabbits, respectively). IL-8 and MCP-1 were localized in the synovial tissue in a perivascular pattern and areas of the interstitium and lining, mostly coinciding with cell infiltration. Tenidap also reduced the accumulation of IL-8 and MCP-1 proteins. In cultured synovial and monocytic cells, tumour necrosis factor-alpha (TNF-α) elicited an increase in gene expression of IL-8 (four- and nine-fold, respectively) and MCP-1 (nine- and four-fold, respectively) that was significantly reversed in both cell types by 10 μm tenidap. These results suggest that the beneficial effect of tenidap in acute

  18. In vivo electrochemical corrosion study of a CoCrMo biomedical alloy in human synovial fluids.

    PubMed

    Igual Munoz, A; Schwiesau, J; Jolles, B M; Mischler, S

    2015-07-01

    The present study was initiated with the aim to assess the in vivo electrochemical corrosion behaviour of CoCrMo biomedical alloys in human synovial fluids in an attempt to identify possible patient or pathology specific effects. For this, electrochemical measurements (open circuit potential OCP, polarization resistance Rp, potentiodynamic polarization curves, electrochemical impedance spectroscopy EIS) were carried out on fluids extracted from patients with different articular pathologies and prosthesis revisions. Those electrochemical measurements could be carried out with outstanding precision and signal stability. The results show that the corrosion behaviour of CoCrMo alloy in synovial fluids not only depends on material reactivity but also on the specific reactions of synovial fluid components, most likely involving reactive oxygen species. In some patients the latter were found to determine the whole cathodic and anodic electrochemical response. Depending on patients, corrosion rates varied significantly between 50 and 750 mg dm(-2)year(-1).

  19. 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.

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

    PubMed Central

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

    1998-01-01

    OBJECTIVES—To examine the effects of ceramide, which is a lipid second messenger of cell surface receptors, including tumour necrosis factor α (TNFα), interleukin 1 (IL1), and Fas receptors, on rheumatoid arthritis (RA) synovial cells.
METHODS—Synovial cells from RA patients and normal skin fibroblasts were cultured with cell permeable ceramide (C2-ceramide). Apoptosis was assessed by microscopic observation of morphological changes, nuclear staining, and DNA electrophoresis. DNA synthesis was examined by thymidine incorporation.
RESULTS—C2-ceramide induced reversible morphological changes of synovial cells such as cell rounding within four hours. Subsequently, irreversible nuclear changes characteristic to apoptosis were observed at 48 hours. DNA synthesis was not promoted. The addition of ceramide exerted similar effects on cultured dermal fibroblasts.
CONCLUSION—Ceramide induced apoptosis in RA synovial cells. Ceramide could be a second messenger specific for apoptosis of RA synovial cells.

 Keywords: ceramide; apoptosis; rheumatoid arthritis PMID:9797556

  1. Novel cartilage oligomeric matrix protein (COMP) neoepitopes identified in synovial fluids from patients with joint diseases using affinity chromatography and mass spectrometry.

    PubMed

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

    2014-07-25

    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 SDSPAGE 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.

  2. 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

  3. Septic versus inflammatory arthritis: discriminating the ability of serum inflammatory markers.

    PubMed

    Talebi-Taher, Mahshid; Shirani, Fatemeh; Nikanjam, Najmeh; Shekarabi, Mehdi

    2013-02-01

    Early diagnosis of septic arthritis is very important. Few studies showed diagnostic accuracy of serum inflammatory markers in septic arthritis. The aim of our study was to compare the serum and synovial fluid markers [procalcitonin, serum IL-6, TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts and PMN percentage] in septic and inflammatory arthritis. Seventy-five patients, including 25 and 50 septic and non-septic arthritis, were enrolled in the study. The serum and synovial fluid markers [procalcitonin, serum IL-6, TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts, and PMN percentage] were compared in septic and inflammatory arthritis. Patients with septic arthritis had significantly elevated levels of procalcitonin, serum TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts, and PMN percentage in comparison with the inflammatory arthritis group (P < 0.00). Serum IL-6 level does not differ among the two groups. In a receiver operating characteristic curve analysis, synovial fluid WBC counts, PMN percentage, TNF-α, ESR, and serum PCT preformed best in distinguishing between septic and non-septic arthritis. Our study suggests that PCT can be used to diagnose the septic arthritis, but more studies warranted in order to determine the specificity and sensitivity of the test.

  4. β-NGF and β-NGF receptor upregulation in blood and synovial fluid in osteoarthritis.

    PubMed

    Montagnoli, Claudia; Tiribuzi, Roberto; Crispoltoni, Lucia; Pistilli, Alessandra; Stabile, Anna Maria; Manfreda, Francesco; Placella, Giacomo; Rende, Mario; Cerulli, Giuliano

    2017-03-02

    Osteoarthritis (OA) of the knee is the most common form of non traumatic joint disease. Previous studies have shown the involvement of β-NGF and its receptors TrKA and p75NTR in OA-related pain, but their role in its pathogenesis is still unclear. The aim of our study was to investigate the amount of β-NGF and the expression levels of its receptors on cells isolated from synovial fluid and blood from OA patients who had undergone total knee arthroplasty, in order to check any possible correlation with the disease staging. Our results show a progressive stage-related increase of β-NGF and its receptors both in serum and synovial fluid. Furthermore, respect to control subjects, OA patients show an increased amount of inflammatory monocytes along with an increased expression of β-NGF, TrKA and p75NTR. In conclusion, our study suggests a stage-related modulation of β-NGF and its receptors in the inflammatory process of OA.

  5. Analysis of the cytokine profiles of the synovial fluid in a normal temporomandibular joint: preliminary study.

    PubMed

    Kim, Young-Kyun; Kim, Su-Gwan; Kim, Bum-Soo; Lee, Jeong-Yun; Yun, Pil-Young; Bae, Ji-Hyun; Oh, Ji-Su; Ahn, Jong-Mo; Kim, Jae-Sung; Lee, Sook-Young

    2012-12-01

    The purpose of this study was to compare the cytokine profiles of the synovial fluid from the temporomandibular joint (TMJ) spaces of normal individuals and temporomandibular disorder (TMD) patients. Thirty-four patients with planned orthognathic surgery did not present abnormalities of the TMJ on magnetic resonance images and radiographs and did not show the symptoms identified by the Research Diagnostic Criteria for TMD (RDC-TMD); as a result, they were assigned to the control group. Twenty-two patients who sought treatment for TMD during the same period were assigned to the TMD group. Synovial fluid was collected from superior TMJ spaces, and cytokine expression was analysed by an enzyme-linked immunosorbent assay (ELISA). Significant differences were tested using Fisher's exact test (p<0.05). Granulocyte Macrophage Colony stimulating Factor (GM-CSF), interferon (INF), interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α were detected in the TMD group, whereas no cytokines were detected in the control group. The most prevalent cytokines in the TMD group were IL-1β, IL-6 and GM-CSF. IL-4 and IL-5 were not detected in either the TMD group or in the control group. None of the cytokines that were detected in patients with TMD were found in the articular spaces of normal individuals.

  6. Lubricin in synovial fluid of mild and severe temporomandibular joint internal derangements

    PubMed Central

    Perrotta, Rosario E.; Almeida, Luis-Eduardo; Loreto, Carla; Musumeci, Giuseppe

    2016-01-01

    Background To understand the molecular basis of temporomandibular joint (TMJ) pathologies, we aimed to investigate the lubricin levels in the TMJ synovial fluid (SF) of patients with mild to severe internal derangements (IDs). Material and Methods A total, 34 joints were the study group. Only patients, with a Wilkes stage of III, IV and V were included, in this sample. Control group consisted of SF from eight joints, from patients undergoing to orthognatic surgery. Concentrations of lubricin in the SF from both samples were measured using ELISA system. Results The mean lubricin concentration was 7.029 ± 0.21 µg/mL in stage III patients; 5.64 ± 0.10 µg/mL in stage IV patients, and 4.78 ± 0.11 µg/mL in stage V patients. The lubricin levels from stage IV and stage V patients differed significantly (P ≤ 0.001) from those of control subjects. Lubricin levels were inversely correlated with age and to VAS score. Conclusions The results of this cross-sectional study highlight the relationship between disease severity and the levels of lubricin in TMJ SF. Our findings suggest that novel biotherapeutic approaches, including the administration of recombinant lubricin in the joint cavity, for the treatment of TMJ diseases can be developed. Key words:Lubricin, TMJ, derangements, synovial fluid. PMID:27694778

  7. 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).

  8. 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

  9. 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

  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

    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.

  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 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

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

    PubMed

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

    1996-08-01

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

  13. Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis

    PubMed Central

    Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

    2017-01-01

    Objectives: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management. PMID:27992368

  14. 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

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

    PubMed

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

    2016-02-12

    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 μm(2)/s, N = 5) than in samples from patients with joint damage (ICRS-score > 2) (4.5 μm(2)/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.

  16. Phospholipid compositions of sera and synovial fluids from dog, human and horse: a comparison by 31P-NMR and MALDI-TOF MS.

    PubMed

    Fuchs, B; Bondzio, A; Wagner, U; Schiller, J

    2009-08-01

    Alterations of the phospholipid (PL) compositions of body fluids are assumed to be indicative of inflammatory diseases, e.g. rheumatoid arthritis (RA). Recently, we have shown that particularly the phosphatidylcholine/lysophosphatidylcholine (PC/LPC) ratio determined in human synovial fluids (SF) and sera represents a reliable measure of the inflammatory state in RA patients. However, it is not yet clear to what extent the PC/LPC ratio is also affected by nutrition habits. In the present study, the PL and the corresponding acyl chain compositions of human body fluids (SF and serum of RA patients as well as serum from healthy volunteers) are compared with those of two other mammalian species (horses and dogs suffering from degenerative joint diseases as well as healthy controls) by high-resolution 31P-nuclear magnetic resonance (NMR) spectroscopy and matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS). The most important result of this study is that the PL compositions of SF and serum of horse and dog are comparable with those of human body fluids. Compared with humans, however, the horse body fluid contains less PCs with highly unsaturated arachidonoyl residues, while that of dogs possesses the highest content of arachidonoyl-containing PC. These species-related differences stem primarily from different nutrition habits (meat vs. plants).

  17. Post-mortem alcohol analysis in synovial fluid: an alternative method for estimation of blood alcohol level in medico-legal autopsies?

    PubMed

    Büyük, Yalçin; Eke, Murat; Cagdir, A Sadi; Karaaslan, Hicran K

    2009-06-01

    To evaluate the effectiveness of synovial fluid alcohol concentration in prediction of blood alcohol concentration, synovial fluid and blood was studied of 50 autopsy cases and the alcohol levels determined by using Head Space Gas Chromatography method. To exclude the effect of decomposition on alcohol levels, corpses with post-mortem intervals less than 24 hours and not showing signs of decomposition were selected. Of 50 cases, alcohol was detected in 15 cases both in blood and in synovial fluid. In 35 cases alcohol analysis was negative both in blood and synovial fluid. No false positive results were seen in terms of synovial fluid. In two of the 15 cases, the alcohol determined was methyl alcohol and in others the alcohol was ethyl alcohol. In these 15 cases, only in one case was SAC level lower than the BAC level, and in 14 cases; SAC levels were higher than those of BAC. BAC (Blood Alcohol Concentration)/SAC (Synovial Fluid Alcohol Concentration) ratios were determined, and in 13 ethanol cases the mean ratio was determined to be 0.95 (0.90 +/- 0.07). The regression analysis showed a fairly linear relationship between the BAC and SAC, with a correlation coefficient of 0.984 (y = 0.86x + 10.4). The present study demonstrates that the synovial fluid is a valuable body fluid that can be used in prediction of blood alcohol concentration in forensic autopsy cases in which blood can not be properly obtained.

  18. 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.

  19. Cytokine profile in the synovial fluid of patients with temporomandibular joint disorders: A systematic review.

    PubMed

    Kellesarian, Sergio Varela; Al-Kheraif, Abdulaziz A; Vohra, Fahim; Ghanem, Alexis; Malmstrom, Hans; Romanos, Georgios E; Javed, Fawad

    2016-01-01

    The aim of this study was to review the cytokine profiles in the synovial fluid (SF) of patients with temporomandibular joint disorders (TMJD). Databases were searched from 1965 till September 2015 using different combinations of the following key words: "Temporomandibular joint"; "Cytokine"; "disorder"; and "synovial fluid" and "inflammation". Titles and abstracts of studies identified using the above-described protocol were screened and checked for agreement. Full-texts of articles judged by title and abstract to be relevant were read and independently evaluated. Hand-searching of the reference lists of potentially relevant original and review articles was also performed. The pattern of the present systematic review was customized to mainly summarize the relevant data. Fifteen studies were included. In 12 studies, cytokine profile of patients with TMJD was assessed using enzyme linked immunosorbent assay; and in 2 studies, histological analysis was performed to assess the cytokine profile of patients with TMJD. Patients with TMJD presented raised levels of interleukin (IL)-6 in 8 studies, IL-1beta (1β) in 5 studies and tumor necrosis factor-alpha (TNF-α) in 5 studies. Two studies showed no significant difference in TNF-α levels in patients with and without TMJD; and IL-1β levels were comparable in patients with and without TMJD in 2 studies. Raised levels of IL-6, TNF-α, IL-1β, IL-8, and IFN-γ in the SF have been associated with inflammation in patients with TMJD. Cytokines IL-10, osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG), and VEGF found in the SF of TMJs could have an anti-inflammatory effect.

  20. 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.

  1. 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.

  2. 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.

  3. Effects of exercise therapy on knee joint function and synovial fluid cytokine levels in patients with knee osteoarthritis.

    PubMed

    Zhang, Shao-Lan; Liu, Hong-Qi; Xu, Xiao-Zu; Zhi, Juan; Geng, Jiao-Jiao; Chen, Jin

    2013-01-01

    The aims of this study were to observe the effect of exercise therapy on the function of the knee joint and the levels of cytokines and cytokine-related genes, specifically tumor necrosis factor-α (TNF-α), high sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-3 (MMP-3), in the synovial joints of patients with knee osteoarthritis (KOA) and to explore its mechanism of action. A total of 100 KOA patients were divided into a treatment group (n=50) and a control group (n=50) according to the order of admission. The patients in the treatment group were treated with diclofenac sodium combined with exercise therapy and the patients in the control group were treated with diclofenac sodium only. The function of the knee joint and the therapeutic efficacy was evaluated and the TNF-α, hs-CRP and MMP-3 levels in the synovial fluid were measured following 4 weeks of treatment. The results revealed that the knee joint index score and the TNF-α, hs-CRP and MMP-3 levels in the synovial fluid decreased significantly in the KOA patients of the two groups following treatment (P<0.05). Compared with the control group, the knee joint index score and the TNF-α, hs-CRP and MMP-3 levels in the synovial joints were lower and the therapeutic efficacy was increased in the patients of the treatment group (P<0.05). In brief, exercise therapy may decrease cytokine and cytokine-related gene levels in the synovial fluid and inhibit inflammatory factor-mediated cartilage degradation in KOA patients, thus, effectively improving the clinical symptoms of KOA.

  4. Altered expression of TPP1 in fibroblast-like synovial cells might be involved in the pathogenesis of rheumatoid arthritis.

    PubMed

    Qing, Yu-Feng; Zhou, Jing-Guo; Zhao, Ming-Cai; Xie, Wen-Guang; Yang, Qi-Bin; Xing, Yan; Zeng, Sheng-Ping; Jiang, Hong

    2012-08-01

    We undertook this study to determine whether the altered expression of telomeric proteins TPP1 and POT1 in fibroblast-like synovial cells (FLS) could provide insights into the pathogenesis of rheumatoid arthritis (RA). FLS were isolated from patients with RA, osteoarthritis (OA) and traumatic joint disease, and cultured in vitro. TPP1 and POT1 mRNA level of FLS were measured using real-time quantitative polymerase chain reaction (RT-qPCR) in 42 RA, 23 OA and 13 healthy cases. Immunofluorescence staining and Western blot were used to detect the expression of TPP1 and POT1 protein. Expression of TPP1 and POT1 mRNA was significantly reduced in RA cases (P < 0.001, respectively), and no significant difference was observed between OA and healthy cases (P > 0.05, respectively). Confocal microscopy images showed TPP1 and POT1 proteins mainly located in nucleus of FLS. Western blot demonstrated that TPP1 protein level was significantly reduced in RA cases (P < 0.001), and POT1 protein expression was not statistical significance among RA, OA patients and healthy cases (P > 0.05). Significant negative correlation was observed between level of TPP1 mRNA and titers of anti-CCP antibody (P < 0.001), RF (P < 0.01). Altered expression of TPP1 might contribute to persistent proliferation of FLS in RA, further study on functions of telomeric proteins in RA would be needed.

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

    PubMed

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

    2015-03-01

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

  6. Women with osteoarthritis have elevated synovial fluid levels of insulin-like growth factor (IGF)-1 and IGF-binding protein-3.

    PubMed

    Hooshmand, Shirin; Juma, Shanil; Khalil, Dania A; Shamloufard, Pouneh; Arjmandi, Bahram H

    2015-01-01

    The present study explores the possible connection between synovial fluid concentrations of insulin like growth factor (IGF-1), IGF-binding protein (IGFBP-3), leptin, and C-reactive protein (CRP) in osteoarthritis (OA). Synovial fluid specimens were obtained from a total of thirty-four individuals with and without OA. Protein-normalized measurements of IGF-1, IGFBP-3, and leptin concentrations in synovial fluid showed significantly (P < 0.05) elevated levels in women with knee OA but not in men. This study provides initial evidence that protein normalized IGF-1 and IGFBP-3 and leptin levels increase in synovial fluid of women but not in men with OA versus those without OA.

  7. Tumor Necrosis Factor-α in Temporomandibular Joint Synovial Fluid Predicts Treatment Effects on Pain by Intra-Articular Glucocorticoid Treatment

    PubMed Central

    Fredriksson, Lars; Alstergren, Per; Kopp, Sigvard

    2006-01-01

    The aim of this study was to investigate the influence of tumor necrosis factor-α (TNF-α) in temporomandibular joint (TMJ) synovial fluid and blood on the treatment effect on TMJ pain by intra-articular injection of glucocorticoid in patients with chronic inflammatory TMJ disorders. High pretreatment level of TNF-α in the synovial fluid was associated with a decrease of TNF-α and elimination of pain upon maximal mouth opening. Elimination of this TMJ pain was accordingly associated with decrease in synovial fluid level of TNF-α. There was also a significant decrease of C-reactive protein and TMJ resting pain after treatment. In conclusion, this study indicates that presence of TNF-α in the synovial fluid predicts a treatment effect of intra-articular injection of glucocorticoid on TMJ movement pain in patients with chronic TMJ inflammatory disorders. PMID:17392588

  8. Serum amyloid A isoforms in serum and synovial fluid from spontaneously diseased dogs with joint diseases or other conditions.

    PubMed

    Kjelgaard-Hansen, Mads; Christensen, Michelle B; Lee, Marcel H; Jensen, Asger L; Jacobsen, Stine

    2007-06-15

    Serum amyloid A (SAA) is a major acute phase protein in dogs. However, knowledge of qualitative properties of canine SAA and extent of its synthesis in extrahepatic tissues is limited. The aim of the study was to investigate expression of different SAA isoforms in serum and synovial fluid in samples obtained from dogs (n=16) suffering from different inflammatory or non-inflammatory conditions, which were either related or unrelated to joints. Expression of SAA isoforms was visualized by denaturing isoelectric focusing and Western blotting. Serum amyloid A was present in serum from all dogs with systemic inflammatory activity, and up to four major isoforms with apparent isoelectric points between 6.1 and 7.9 were identified. In synovial fluid from inflamed joints one or more highly alkaline SAA isoforms (with apparent isoelectric points above 9.3) were identified, with data suggesting local production of these isoforms in the canine inflamed joint.

  9. Interleukin 2 (IL 2) inhibitor in rheumatoid synovial fluid: Correlation with prognosis and soluble IL 2 receptor levels

    SciTech Connect

    Miossec, P.; Elhamiani, M.; Chichehian, B.; D'Angeac, A.D.; Sany, J.; Hirn, M. )

    1990-03-01

    A soluble activity inhibiting over 50% of the CTLL-2 cell line response to recombinant human interleukin 2 (IL 2) was found in 17 of 29 (59%) rheumatoid synovial fluids. To study the prognosis value of this activity, 16 rheumatoid synovial fluids were collected before a radiation synovectomy of the knee with 7 mCi of 90Y. Patients with a good clinical result after the synovectomy had a lower IL 2 inhibitory activity than those with a bad or incomplete result (P less than 0.01). Levels of inhibitory activity and of soluble IL 2 receptors were correlated with each other and with the response of the synovitis to the radiation synovectomy. These results extend the clinical usefulness of soluble IL 2 receptor measurements and indicate a correlation between the immune activation of the rheumatoid synovitis and its clinical activity.

  10. Expression and Functions of Immediate Early Response Gene X-1 (IEX-1) in Rheumatoid Arthritis Synovial Fibroblasts

    PubMed Central

    Morinobu, Akio; Tanaka, Shino; Nishimura, Keisuke; Takahashi, Soshi; Kageyama, Goichi; Miura, Yasushi; Kurosaka, Masahiro; Saegusa, Jun; Kumagai, Shunichi

    2016-01-01

    In rheumatoid arthritis (RA), synovial fibroblasts (RA-SFs) accumulate in affected joints, where they play roles in inflammation and joint destruction. RA-SFs exhibit tumor-like proliferation and are resistant to apoptosis. Although RA-SF activation is well described, negative regulators of RA-SF activation are unknown. We previously reported that histone deacetylase (HDAC) inhibitors facilitate apoptosis in RA-SFs. Here we found that RA-SFs treated with the HDAC inhibitor Trichostatin A (TSA) exhibited an upregulation of the immediate early response gene X-1 (IEX-1). IEX-1 has roles in apoptosis sensitivity, cell-cycle progression, and proliferation, and is reported to be involved in immune responses, inflammation, and tumorigenesis, and to have anti-arthritic properties. To investigate IEX-1’s role in RA-SFs, we used in vitro-cultured synovial fibroblasts from RA and osteoarthritis (OA) patients. We confirmed that TSA upregulated the IEX-1 protein and mRNA expressions in RA-SFs by western blotting and quantitative RT-PCR. Inhibiting HDAC1, 2, and 3 (but not 6 or 8) also upregulated IEX-1. The IEX-1 mRNA levels were higher in RA-SFs than in OA-SFs, and were further upregulated in RA-SFs by the pro-inflammatory cytokines TNFα and IL-1β. The staining of surgical specimens showed that IEX-1 was present in the pannus from affected RA joints. Si-RNA-mediated IEX-1 knockdown upregulated the lipopolysaccharide (LPS)-induced expression of TNFα and various chemokine mRNAs, indicating that IEX-1 downregulates TNFα and chemokines. Furthermore, apoptosis analysis showed that IEX-1 knockdown protected RA-SFs from apoptosis induced by TSA or by an anti-Fas mAb, indicating that IEX-1 is pro-apoptotic in RA-SFs. Collectively, our results showed that IEX-1 is induced by TNFα and IL-1β in RA-SFs, in which it suppresses TNFα and chemokine production and induces apoptosis; thus, IEX-1 negatively regulates RA-SF activation. Further investigation of IEX1’s functions in RA

  11. 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

  12. Surgical Management of Septic Arthritis.

    PubMed

    Mulon, Pierre-Yves; Desrochers, André; Francoz, David

    2016-11-01

    Lameness related to synovial infection needs to be addressed promptly because rapid degradation of the synovial homeostasis results in permanent cartilage alterations detrimental to complete recovery. Diagnosis is based on clinical signs, synovial fluid analysis, and imaging. Commonly affected joints are the fetlock, carpus, tarsus, and stifle; shoulder, elbow, and hip may also be infected. Knowing the source of infection is essential in cases of remote septic arthritis. Antimicrobials should be administered; local delivery systems may be used. Therapy relies on the removal of inflammatory mediators. Pain management is critical throughout the surgical procedures and the recovery period.

  13. 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.

  14. Delayed examination of synovial fluid by ordinary and polarised light microscopy to detect and identify crystals

    PubMed Central

    Galvez, J; Saiz, E; Linares, L; Climent, A; Marras, C; Pina, M; Castellon, P

    2002-01-01

    Objective: To determine the reliability of a delay in the microscopic examination of synovial fluid (SF) to detect and identify crystals. Methods: Ninety one SF samples were examined, 31 with monosodium urate (MSU) crystals, 30 with crystals of calcium pyrophosphate dihydrate (CPPD), and 30 containing no crystals. The specimens were stored with EDTA, sodium heparin, and without anticoagulant at 4°C before examination at 24 and 72 hours with ordinary and polarised light microscopy. Another aliquot of the same samples was stored in a plastic container without anticoagulant at -80°C and examined after two months. Results: When the samples stored at 4°C were re-examined after 24 hours, intracellular crystals of MSU were seen in 90/93 (97%) cases where they had been identified previously and 89/93 (96%) cases after 72 hours. Similarly, CPPD crystals were identified in 90/90 (100%) and 87/90 (97%) cases after 24 and 72 hours. Examination of the samples stored at -80°C showed intracellular MSU crystals in 25/31 (81%) of cases and CPPD crystals in 25/30 (83%). No crystals were seen in any sample which had previously been diagnosed as crystal-free. Conclusions: Deferred microscopic examination of refrigerated or deep frozen SF provides a strong probability of detecting MSU or CPPD crystals if these are present initially. PMID:11959769

  15. Chemical nature of implant-derived titanium(IV) ions in synovial fluid

    SciTech Connect

    Silwood, Christopher J.L.; Grootveld, Martin . E-mail: grootvm@lsbu.ac.uk

    2005-05-13

    Previous investigations have indicated a deleterious leakage of Ti(III) and/or Ti(IV) species from Ti-Al-V alloy joint prostheses into adjacent tissue, synovium or synovial fluid (SF) in vivo. In view of the importance of the particular chemical nature of such complexes in determining their biological activity, we have employed high field proton ({sup 1}H) NMR spectroscopy to 'speciate' Ti(IV) in inflammatory SF. Treatment of osteoarthritic SF samples with increasing concentrations of Ti(IV) (0.10-1.03 mM [TiO(C{sub 2}O{sub 4}){sub 2}]{sup 2-}) gave rise to a specific broadening of the citrate proton resonances, indicating that this bioavailable oxygen-donor ligand plays an important role in complexing implant-derived Ti(IV). {sup 1}H NMR analysis of Ti(IV)-loaded SF samples subsequently treated with a large excess of ascorbate (0.05 M) showed that this added Ti(IV) chelator was only poorly effective in removing this metal ion from Ti(IV)-citrate/Ti(IV)-oxycitrate complexes. The results obtained here provide evidence for complexation of the low-molecular-mass (non-protein-bound) fraction of implant-derived Ti(IV) by citrate in vivo.

  16. 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.

  17. Lubricin expression in human osteoarthritic knee meniscus and synovial fluid: a morphological, immunohistochemical and biochemical study.

    PubMed

    Musumeci, Giuseppe; Trovato, Francesca Maria; Loreto, Carla; Leonardi, Rosalia; Szychlinska, Marta Anna; Castorina, Sergio; Mobasheri, Ali

    2014-06-01

    The purpose of this study was to investigate the expression of lubricin, the product of the human PRG4 (proteoglycan 4) gene, in menisci and synovial fluid from normal donors and patients with osteoarthritis (OA), using a combination of histology, immunohistochemistry, ELISA and Western blotting analysis, to provide further insight on the role of this protein in the progression of OA and pathological processes in the meniscus. Lubricin expression was studied in samples from 40 patients and in 9 normal donors after arthroscopic partial meniscectomy. Histological analysis confirmed normal microanatomy and the absence of structural changes in control samples. Menisci derived from OA patients showed evidence of structural alterations, fibrillations and clefts. Immunohistochemical analysis revealed very strong lubricin immunostaining in normal menisci in contrast to weak/moderate staining seen in osteoarthritic menisci. Quantitative ELISA and Western blot analysis confirmed the above results. The findings of this study support the notion that changes in lubricin expression and boundary-lubricating ability of cartilage is followed by the development of OA. This study could provide the biological foundation for the development of novel therapeutic treatments, to be applied before the surgery, for the prevention of post-traumatic cartilage damage.

  18. 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

  19. Predictors of Septic Arthritis in the Adult Population.

    PubMed

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

    2016-07-01

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

  20. 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

  1. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study

    PubMed Central

    de Grauw, Janny C; van de Lest, Chris HA; van Weeren, Paul René

    2009-01-01

    Introduction Inflammation is an important feature of many joint diseases, and levels of cartilage biomarkers measured in synovial fluid may be influenced by local inflammatory status. Little is known about the magnitude and time course of inflammation-induced changes in cartilage tissue turnover as measured in vivo by synovial fluid markers. We aimed to study temporal changes in concentrations of inflammatory mediators, matrix metalloproteinase activity and cartilage biomarkers over 1 week in joints with experimentally induced inflammation. Methods Localized inflammation was induced in the intercarpal joint of six horses by sterile injection of 0.5 ng lipopolysaccharide, and synovial fluid was collected at post-injection hours (PIH) 0, 8, 24 and 168. Concentrations of inflammatory mediators (prostaglandin E2, substance P, and bradykinin), general matrix metalloproteinase activity and markers of collagen II turnover (CPII and C2C) as well as aggrecan turnover (CS846 and glycosaminoglycans) were measured with appropriate assays. One-way analysis of variance on repeated measures was used to analyze differences in synovial fluid marker levels over time. Results Lipopolysaccharide-injection led to a sharp rise in prostaglandin E2 at PIH 8, while substance P, bradykinin and matrix metalloproteinase activity showed more sustained increases at PIH 8 and 24. Glycosaminoglycan release paralleled changes in the CS846 epitope, with an increase by PIH 8, a peak at PIH 24, and return to baseline by PIH 168. For type II collagen, a parallel time course between catabolic (C2C) and anabolic (CPII) markers was also observed, but the time course differed from that seen for proteoglycan markers: collagen II markers peaked later, at PIH 24, and were still elevated over baseline at PIH 168. Conclusions A primary intra-articular inflammatory insult, characterized by local release of peptide and lipid mediators and matrix metalloproteinase activation, can alter synovial fluid levels of

  2. 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.

  3. 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

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

    PubMed

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

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

  5. IL33 in rheumatoid arthritis: potencial contribution to pathogenesis.

    PubMed

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

    2016-03-22

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

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

    PubMed

    Connolly, Mary; Marrelli, Alessandra; Blades, Mark; McCormick, Jennifer; Maderna, Paola; Godson, Catherine; Mullan, Ronan; FitzGerald, Oliver; Bresnihan, Barry; Pitzalis, Costantino; Veale, Douglas J; Fearon, Ursula

    2010-06-01

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

  7. 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.

  8. RNA‑seq analysis of synovial fibroblasts in human rheumatoid arthritis.

    PubMed

    Wang, Xiuhui; Xia, Shengli; Fu, Beigang

    2014-07-01

    The aim of the present study was to identify differentially expressed genes (DEGs) between individuals with rheumatoid arthritis (RA) and healthy controls, in order to provide a theoretical foundation for RA diagnosis and targeted gene therapy. Illumina mRNA sequence data (RNA‑Seq) corresponding to RA and control samples were downloaded from the Sequence Read Archive (SRA) database. Gene Ontology (GO) enrichment analysis was performed with the GOstat tool in order to identify over‑represented biological functions among DEGs, and the related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified using the KEGG Automatic Annotation Server (KAAS). A total of 293 DEGs were identified, among which 16 DEGs have been previously shown to associate with RA, such as those encoding matrix metalloproteinase‑1 (MMP‑1), interleukin‑1 receptor type 1 (IL1R1), and chemokine (C-X3-C motif) ligand 1 (CX3CL1). GO functional annotation and enrichment analysis showed that the DEGs are enriched for 309 GO terms, mainly protein‑protein interactions, membrane formation and stability. KEGG pathway analysis demonstrated that these DEGs are involved in 131 pathways, including Wnt and calcium signaling, and cell adhesion molecule (CAM)-related pathways. In conclusion, the results provide both expansive and detailed insights into the molecular pathogenesis of RA, particularly with regards to the development of therapeutic targets, and may inspire further experimentation aiming to identify new strategies for RA treatment.

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

    PubMed

    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.

  10. Acute Molecular Changes in Synovial Fluid Following Human Knee Injury: Association With Early Clinical Outcomes

    PubMed Central

    Paterson, Erin; Freidin, Andrew; Kenny, Mark; Judge, Andrew; Saklatvala, Jeremy; Williams, Andy; Vincent, Tonia L.

    2016-01-01

    Objective To investigate whether molecules found to be up‐regulated within hours of surgical joint destabilization in the mouse are also elevated in the analogous human setting of acute knee injury, how this molecular response varies between individuals, and whether it is related to patient‐reported outcomes in the 3 months after injury. Methods Seven candidate molecules were analyzed in blood and synovial fluid (SF) from 150 participants with recent structural knee injury at baseline (<8 weeks from injury) and in blood at 14 days and 3 months following baseline. Knee Injury and Osteoarthritis Outcome Score 4 (KOOS4) was obtained at baseline and 3 months. Patient and control samples were compared using Meso Scale Discovery platform assays or enzyme‐linked immunosorbent assay. Results Six of the 7 molecules were significantly elevated in human SF immediately after injury: interleukin‐6 (IL‐6), monocyte chemotactic protein 1, matrix metalloproteinase 3 (MMP‐3), tissue inhibitor of metalloproteinases 1 (TIMP‐1), activin A, and tumor necrosis factor–stimulated gene 6 (TSG‐6). There was low‐to‐moderate correlation with blood measurements. Three of the 6 molecules were significantly associated with baseline KOOS4 (those with higher SF IL‐6, TIMP‐1, or TSG‐6 had lower KOOS4). These 3 molecules, MMP‐3, and activin A were all significantly associated with greater improvement in KOOS4 over 3 months, after adjustment for other relevant factors. Of these, IL‐6 alone significantly accounted for the molecular contribution to baseline KOOS4 and change in KOOS4 over 3 months. Conclusion Our findings validate relevant human biomarkers of tissue injury identified in a mouse model. Analysis of SF rather than blood more accurately reflects this response. The response is associated with patient‐reported outcomes over this early period, with SF IL‐6 acting as a single representative marker. Longitudinal outcomes will determine if these molecules are

  11. Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid.

    PubMed

    Céleste, Christophe; Ionescu, Mirela; Robin Poole, A; Laverty, Sheila

    2005-05-01

    Although intraarticular (IA) corticosteroids are frequently used to treat joint disease, the effects of their repeated use on articular cartilage remains controversial. The aim of our study was to determine the effects of a clinically recommended dose of IA triamcinolone acetonide (TA), on synovial fluid (SF) biomarkers of cartilage metabolism. Ten adult horses, free of osteoarthritis (OA) in their radiocarpal joints, were studied. One radiocarpal joint of each horse was randomly chosen for treatment and the contralateral anatomically paired joint acted as the control. Aseptic arthrocentesis was performed weekly on both joints for 13 weeks. The initial results from the first 3 weeks of the experimental period established baseline untreated control marker levels for each joint, each being its own control. On weeks 3, 5, and 7, a sterile suspension of 12 mg of TA was injected into the treated joint and an equivalent volume of sterile saline solution (0.9%) was injected into the control joint. SF was immunoassayed for biomarkers of aggrecan turnover (CS 846 & KS), types I and II collagen cleavage (C1,2C) and type II collagen synthesis (CPII). In treated joints, there was a significant increase in CS 846, KS, C1,2C and CPII epitope concentrations following IA TA injections when compared to baseline levels. There was also a significant increase in C1,2C and CPII epitope concentrations in the contralateral control joints following IA TA injections in the treated joint. Significant differences were observed between treated and control joints for all markers except CPII. These findings indicate that TA alters articular cartilage and collagen metabolism in treated and, interestingly, also in control joints, suggesting a systemic effect of the drug. Though intuitively the observed findings would favor the hypothesis that long-term IA TA treatment changes joint metabolism and this may have detrimental effects; further studies would be necessary to confirm this.

  12. The adsorption and lubrication behavior of synovial fluid proteins and glycoproteins on the bearing-surface materials of hip replacements.

    PubMed

    Roba, Marcella; Naka, Marco; Gautier, Emanuel; Spencer, Nicholas D; Crockett, Rowena

    2009-04-01

    The selectivity of synovial fluid protein adsorption onto ultra-high molecular weight polyethylene (UHMWPE) and alumina (Al(2)O(3)), and in particular the ability of glycoproteins to adsorb in the presence of all the other synovial fluid proteins, was investigated by means of fluorescence microscopy and gel electrophoresis (SDS-PAGE). The non-specific nature of protein adsorption from synovial fluid indicated that the lubrication of artificial hip-joint materials may not be attributable to a single protein as has been frequently suggested. The friction behavior of polyethylene (PE) sliding against Al(2)O(3) in solutions of bovine serum albumin (BSA), alpha-1-acid glycoprotein (AGP) and alpha-1-antitrypsin (A1AT) was investigated by means of colloidal probe atomic force microscopy. BSA was shown to be a poorer boundary lubricant than the phosphate buffered saline used as a control. This was attributed to denaturation of the BSA upon adsorption, which provided a high-shear-strength layer at the interface, impairing the lubrication. Interestingly, both the glycoproteins AGP and A1AT, despite their low concentrations, improved lubrication. The lubricating properties of AGP and A1AT were attributed to adsorption via the hydrophobic backbone, allowing the hydrophilic carbohydrate moieties to be exposed to the aqueous solution, thus providing a low-shear-strength fluid film that lubricated the system. The amount of glycoprotein adsorbed on hydrophobic surfaces was determined by means of optical waveguide lightmode spectroscopy (OWLS), allowing conclusions to be drawn about the conformation of the glycan residues following adsorption.

  13. 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.

  14. 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.

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

    PubMed

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

    1999-09-16

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

  16. Exploring time of death from potassium, sodium, chloride, glucose & calcium analysis of postmortem synovial fluid in semi arid climate.

    PubMed

    Siddhamsetty, Arun K; Verma, Satish K; Kohli, Anil; Verma, Aditi; Puri, Dinesh; Singh, Archana

    2014-11-01

    Estimation of time of death (TOD) with fair accuracy from postmortem changes still remains an important but difficult task to be performed by every autopsy surgeon under different climatic conditions. The environment plays an important role in the process of decomposition and thereby affecting the levels of electrolytes and other biochemical parameters in the postmortem samples. Since, there is limited information available on the levels of these biochemical parameters from semi arid environment, the present study was aimed to explore time of death by analyzing electrolyte, glucose and calcium levels of postmortem synovial fluid collected from samples under such climatic conditions. The synovial fluid samples from two hundred and ten bodies brought to University College of Medical Sciences and associated Guru Teg Bahadur Hospital Delhi for medico-legal postmortem examination, during the period of November 2010 to April 2012, were analyzed for potassium, sodium, chloride, glucose and calcium. Univariate regression analysis of electrolyte concentrations of synovial fluid showed significant positive relationship between time of death and potassium (r = 0.840, p = 0.000). However, there was negative relationship between time of death and sodium (r = -0.175, p = 0.011) & glucose (r = -0.427, p = 0.000) and no significant relationship was found between time of death and calcium (r = 0.099, p = 0.152) & chloride (r = 0.082, p = 0.24) among the samples analyzed.

  17. Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.

    PubMed

    Knych, Heather K; Harrison, Linda M; White, Alexandria; McKemie, Daniel S

    2016-01-01

    The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various times up to 28 days post drug administration. All samples were analyzed using liquid chromatography-Mass Spectrometry. Plasma data were analyzed using a population pharmacokinetic compartmental model. Maximum measured plasma isoflupredone concentrations were 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 h and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 h, respectively, for horses that had synovial fluid collected and for those that did not. The plasma beta half-life was 24.2 h. Isoflupredone concentrations were below the limit of detection in all horses by 48 h and 7 days in plasma and urine, respectively. Isoflupredone was detected in the right antebrachiocarpal and middle carpal joints for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively. Results of this study provide information that can be used to regulate the use of intra-articular isoflupredone in the horse.

  18. Enhanced expression of heat shock protein 70 (hsp70) and heat shock factor 1 (HSF1) activation in rheumatoid arthritis synovial tissue. Differential regulation of hsp70 expression and hsf1 activation in synovial fibroblasts by proinflammatory cytokines, shear stress, and antiinflammatory drugs.

    PubMed Central

    Schett, G; Redlich, K; Xu, Q; Bizan, P; Gröger, M; Tohidast-Akrad, M; Kiener, H; Smolen, J; Steiner, G

    1998-01-01

    Heat shock proteins (hsp) have been repeatedly implicated to participate in the pathogenesis of rheumatoid arthritis (RA). Herein, we investigated the regulation of synovial hsp70 expression by analyzing the DNA-binding activity of heat shock transcription factor 1 (HSF1) as well as inducible hsp70 expression. Experiments were performed both on synovial tissue and on synovial fibroblast-like cells (SFC). Gel mobility shift analysis revealed increased HSF1 activation, and Western blotting and immunohistochemistry revealed increased hsp70 expression in RA synovial tissue, but not in synovial tissue derived from patients with osteoarthritis. Proinflammatory cytokines (TNF-alpha, IL-1alpha, IL-6), but not IFN-gamma or TGF-beta, induced activation of HSF1-DNA binding and hsp70 expression in cultivated SFC. Activation of HSF1 in SFC was accompanied by hyperphosphorylation and nuclear translocation of HSF1. Furthermore, shear stress also induced a complete heat shock response in cultivated synovial cells. In contrast, nonsteroidal antiinflammatory drugs triggered only an incomplete heat shock response, with HSF1 activation but not hsp70 induction, whereas steroids and immunosuppressive drugs did not affect the heat shock response at all. In summary, these data suggest that induction of hsp70 expression in rheumatoid synovial tissue is based on transcriptional activation of HSF1 due to the presence of proinflammatory cytokines (and possibly also shear stress). PMID:9664071

  19. Influence of C3 level on the determination of C3d in plasma and synovial fluid by radial immunodiffusion.

    PubMed

    Hack, C E; Paardekooper, J; Hannema, A J

    1986-02-12

    The influence of C3 levels on the determination of C3d in plasma and synovial fluid by radial immunodiffusion was investigated. In the method used, C3 is precipitated by 11% polyethylene glycol (PEG), and C3d is measured in the supernatant. In 51 healthy donors, a weak though significant correlation between C3 and C3d levels was found. The mean concentration of C3d was 1.6% of that in aged serum from healthy donors. So, small amounts of C3 (i.e., 1-2% of the normal plasma level) in the 11% PEG supernatants may contribute significantly to the C3d levels measured. A radioimmunoassay that detects C3, C3b, iC3b and C3c was used to measure C3 levels in the PEG supernatants. In PEG supernatants of 4 plasma samples, 0.3-0.6% of the C3 level in normal plasma was found, whereas in those of 2 synovial fluids much higher levels were found (4-10% of the normal plasma level). When purified 125I-labeled antibodies against C3c were added to the gel of the radial immunodiffusion, C3c antigen was detected in the precipitation rings obtained with all PEG supernatants of plasma samples from patients. Therefore, the quantitative contribution of C3 to the precipitation rings in the C3d radial immunodiffusion was analyzed after the addition of an excess of anti-C3c antibodies to the gel. No effect on the size of the C3d-precipitation rings obtained with plasma samples from patients was observed. However, the C3d precipitation rings obtained with synovial fluids were significantly smaller when the gel used in the radial immunodiffusion contained an excess of anti-C3c antibodies together with the anti-C3d serum. We conclude that it is necessary to add an excess of anti-C3c antibodies to the gel used for the radial immunodiffusion, for the determination of C3d levels in synovial fluid. An antiserum against human C3b, which contains both anti-C3c and anti-C3d antibodies, can be used for this purpose.

  20. Effects of loading concentration, blood and synovial fluid on antibiotic release and anti-biofilm activity of bone cement beads.

    PubMed

    Dusane, Devendra H; Diamond, Scott M; Knecht, Cory S; Farrar, Nicholas R; Peters, Casey W; Howlin, Robert P; Swearingen, Matthew C; Calhoun, Jason H; Plaut, Roger D; Nocera, Tanya M; Granger, Jeffrey F; Stoodley, Paul

    2017-02-28

    Antibiotic loaded cement beads are commonly used for the treatment of biofilm related orthopaedic periprosthetic infections; however the effects of antibiotic loading and exposure of beads to body fluids on release kinetics are unclear. The purpose of this study was to determine the effects of (i) antibiotic loading density (ii) loading amount (iii) material type and (iv) exposure to body fluids (blood or synovial fluid) on release kinetics and efficacy of antibiotics against planktonic and lawn biofilm bacteria. Short-term release into an agar gel was evaluated using a fluorescent tracer (fluorescein) incorporated in the carrier materials calcium sulfate (CaSO4) and poly methyl methacrylate (PMMA). Different fluorescein concentrations in CaSO4 beads were evaluated. Mechanical properties of fluorescein-incorporated beads were analyzed. Efficacy of the antibiotics vancomycin (VAN) or tobramycin (TOB) alone and in combination was evaluated against lawn biofilms of bioluminescent strains of Staphylococcus aureus and Pseudomonas aeruginosa. Zones of inhibition of cultures (ZOI) were measured visually and using an in-vivo imaging system (IVIS). The influence of body fluids on release was assessed using CaSO4 beads that contained fluorescein or antibiotics and were pre-coated with human blood or synovial fluid. The spread from the beads followed a square root of time relationship in all cases. The loading concentration had no influence on short-term fluorescein release and pre-coating of beads with body fluids did not affect short-term release or antibacterial activity. Compared to PMMA, CaSO4 had a more rapid short term rate of elution and activity against planktonic and lawn biofilms. This study highlights the importance of considering antibiotic loading and packing density when investigating the clinical application of bone cements for infection management.

  1. Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis

    PubMed Central

    Qing, Liming; Lei, Pengfei; Liu, Hao; Xie, Jie; Wang, Long; Wen, Ting; Hu, Yihe

    2017-01-01

    The aim of the present study was to examine hypoxia-inducible factor 1α (HIF-1α) levels in the synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and to investigate their association with the severity of disease. A total of 36 patients with knee OA and ten healthy controls were enrolled. Anteroposterior knee radiographs and/or Mankin scores were assessed to determine the disease severity of the affected knee. Radiographic grading of OA in the knee was performed according to Kellgren-Lawrence criteria. HIF-1α levels in synovial fluid were measured using enzyme-linked immunosorbent assay, whereas HIF-1α levels in articular cartilage were assessed with immunohistochemical methods. Compared with healthy controls, OA patients exhibited an increased HIF-1α concentration in synovial fluid (218.17±25.12 vs. 156.66±7.74 pg/ml; P<0.001) and articular cartilage (P<0.05). Furthermore, synovial fluid HIF-1α levels demonstrated a positive correlation with articular cartilage HIF-1α levels (Pearson's P=0.815; P<0.001). Subsequent analysis showed that synovial fluid HIF-1α levels were significantly correlated with the severity of disease (Spearman's ρ=0.933; P<0.001). Furthermore, articular cartilage levels of HIF-1α also correlated with disease severity (Spearman's ρ=−0.967; P<0.001). The findings of the present study suggested that HIF-1α in synovial fluid and articular cartilage is associated with progressive joint damage and is likely to be a useful biomarker for determining disease severity and progression in knee OA. PMID:28123469

  2. 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

  3. 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

  4. Lubrication of the human ankle joint in walking with the synovial fluid filtrated by the cartilage with the surface zone worn out: steady pure sliding motion.

    PubMed

    Hlavácek, M

    1999-10-01

    A mixture model of synovial fluid filtration by cartilage in the human ankle joint during walking is presented for steady sliding motion of the articular surfaces. In the paper the cartilage surface zone is assumed worn out. The same model has been recently applied to the squeeze-film problem for the human hip joint loaded by the body weight during standing (Hlavácek, Journal of Biomechanics 26, 1145-1150, 1151-1160, 1993; Hlavácek and Novák, Journal of Biomechanics 28, 1193-1198, 1199-1205, 1995). The linear biphasic model for cartilage (elastic porous matrix + ideal fluid) due to Prof. V. C. Mow and his co-workers and the biphasic model for synovial fluid (viscous fluid + ideal fluid), as used in the above-mentioned squeeze-film problem, are applied. For the physiologic parameters of the ankle joint during walking, a continuous synovial fluid film about 1 microm thick is maintained under steady entraining motion according to the classical model without the fluid transport across the articular surface. This is not the case in the filtration model with the cartilage surface zones worn out. On the contrary, this filtration model indicates that synovial fluid is intensively filtrated by such cartilage, so that no continuous fluid film is maintained and a synovial gel layer, about 10(-8) m thick, develops over the majority of the contact. Thus, if the cartilage surface zones are worn out, boundary lubrication should prevail in the ankle joint under steady sliding motion for the mean values of loading and the sliding velocity encountered in walking cycle.

  5. Systemic TNF blockade does not modulate synovial expression of the pro-inflammatory mediator HMGB1 in rheumatoid arthritis patients – a prospective clinical study

    PubMed Central

    Sundberg, Erik; Grundtman, Cecilia; af Klint, Erik; Lindberg, Johan; Ernestam, Sofia; Ulfgren, Ann-Kristin; Harris, Helena Erlandsson; Andersson, Ulf

    2008-01-01

    Introduction High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an endogenous mediator of arthritis. TNF and IL-1β, pivotal cytokines in arthritis pathogenesis, both have the ability to induce the release of HMGB1 from myeloid and dendritic cells. It was, therefore, decided to investigate whether treatment based on TNF blockade in rheumatoid arthritis (RA) affects the expression of synovial HMGB1. Methods Repeated arthroscopy-guided sampling of synovial tissue was performed in nine patients with RA before and nine weeks after initiation of anti-TNF mAb (infliximab) therapy. Synovial biopsy specimens were analysed for HMGB1 protein by immunohistochemical staining and for HMGB1 mRNA expression by real-time reverse transcriptase PCR (RT-PCR). Statistical evaluations were based on Wilcoxon's signed rank tests or Spearman rank sum tests. Results Aberrant, extranuclear HMGB1 and constitutive nuclear HMGB1 expression, with histological signs of inflammation, were evident in all biopsies obtained before infliximab therapy. Signs of inflammation were still evident in the second biopsies obtained nine weeks after initiation of infliximab therapy. The cytoplasmic and extracellular expression of HMGB1 decreased in five patients, remained unchanged in one patient and increased in three patients, making the overall change in HMGB1 protein expression not significant. No correlation between the clinical response, as measured by disease activity score calculated for 28 joints (DAS28) or the American College of Rheumatology response criteria (ACR 20, 50, and 70), and the direction of change of HMGB1 expression in individual patients could be discerned. In addition, infliximab therapy did not alter HMGB1 mRNA synthesis. Conclusion Pro-inflammatory HMGB1 expression during rheumatoid synovitis was not consistently influenced by TNF-blocking therapy with infliximab. This suggests that TNF is not the main inducer of extranuclear HMGB1 during synovitis

  6. Correlation between plasma, synovial fluid and articular cartilage Interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee.

    PubMed

    Wang, Youhua; Xu, Dawei; Long, Long; Deng, Xiaolong; Tao, Ran; Huang, Guicheng

    2014-08-01

    Osteoarthritis (OA) is a complex disease characterized by cartilage degeneration, secondary synovial membrane inflammation and subchondral bone changes. In recent years, many studies have confirmed that interleukin-18 (IL-18) is involved in the inflammatory process of inflammatory joint diseases. In the present study, we investigated IL-18 levels in plasma, synovial fluid and articular cartilage of patients with primary knee OA (n = 33) to analyze their relationship with radiographic severity. Compared to healthy controls (n = 15), OA patients had higher plasma and synovial fluid IL-18 concentrations(45.8 ± 22.1 vs. 23.7 ± 13.6 pg/ml, P<0.001 and 75.2 ± 40.1 vs. 28.3 ± 11.6 pg/ml, P<0.001) as measured by enzyme-linked immunosorbent assay. Also,the percentage of immunofluorescent IL-18 positive cells in articular cartilage was significantly increased in OA compared to controls (46.5 ± 10.3 vs. 2.9 ± 1.7, P<0.001). Moreover, plasma, synovial fluid and articular cartilage IL-18 significantly positively correlated with radiographic severity, respectively (r = 0.663, P<0.001, r = 0.56, P = 0.001 and r = 0.884, P<0.001). Subsequent analysis revealed that plasma, synovial fluid and articular cartilage IL-18 levels positively correlated with each other (r = 0.632, P<0.001, r = 0.489, P = 0.004 and r = 0.620, P<0.001). These data suggested that plasma, synovial fluid and articular cartilage IL-18 levels were significantly increased in OA patients, and these elevated levels were positively correlated with radiographic severity. Accordingly, our study supports the role of IL-18 in the pathophysiology of OA.

  7. Infective Arthritis: Bacterial 23S rRNA Gene Sequencing as a Supplementary Diagnostic Method

    PubMed Central

    Moser, Claus; Andresen, Keld; Kjerulf, Anne; Salamon, Suheil; Kemp, Michael; Christensen, Jens Jørgen

    2008-01-01

    Consecutively collected synovial fluids were examined for presence of bacterial DNA (a 700-bp fragment of the bacterial 23S rRNA gene) followed by DNA sequencing of amplicons, and by conventional bacteriological methods. One or more microorganisms were identified in 22 of the 227 synovial fluids (9,7%) originating from 17 patients. Sixteen of the patients had clinical signs of arthritis. For 11 patients molecular and conventional bacterial examinations were in agreement. Staphylococcus aureus, Streptococcus dysgalactiae subspecies equisimilis and Streptococcus pneumoniae, were detected in synovial fluids from 6, 2 and 2 patients, respectively. In 3 patients only 23S rRNA analysis was positive; 2 synovial fluids contained S. dysgalactiae subspecies equisimilis and 1 S. pneumoniae). The present study indicates a significant contribution by PCR with subsequent DNA sequencing of the 23S rRNA gene analysis in recognizing and identification of microorganisms from synovial fluids. PMID:19088916

  8. Receptor activator NF-κB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis

    PubMed Central

    Crotti, T; Smith, M; Weedon, H; Ahern, M; Findlay, D; Kraan, M; Tak, P; Haynes, D

    2002-01-01

    Objectives: To compare receptor activator of NF-κB ligand (RANKL) production in the synovial tissue from patients with active rheumatoid arthritis (RA), inactive RA, spondyloarthropathies (SpA), osteoarthritis, and from normal subjects. In addition, to establish the cell lineages expressing RANKL in these tissues. Methods: Immunohistological analysis of frozen synovial tissue biopsy specimens was performed using a monoclonal antibody (mAb) to detect RANKL. Sections were evaluated by computer assisted image analysis and semiquantitative analysis to compare RANKL expression between groups. Dual and sequential labelling with mAb RANKL and cell lineage specific monoclonal antibodies were used to determine the types of cells expressing RANKL. Results: Higher levels of RANKL were expressed in tissues from patients with active RA and SpA than in tissues from patients with inactive RA, osteoarthritis, and from normal subjects. RANKL protein was associated with CD3 antigen-positive lymphocytes and some macrophages. RANKL was predominantly associated with activated, memory T cells (CD45Ro positive cells) in patients with active RA and spondyloarthropathy (SpA). Conclusions: The highest levels of RANKL were detected in patients with RA with active synovitis and in some patients with SpA. An increase in RANKL in the inflamed joint of patients with RA, produced by infiltrating activated T cells and macrophages, is likely to be an important cause of joint erosions in RA. PMID:12429533

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

    PubMed

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

    2013-10-01

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

  10. 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.

  11. Diagnosis and treatment of Lyme arthritis.

    PubMed

    Arvikar, Sheila L; Steere, Allen C

    2015-06-01

    In the United States, Lyme arthritis is the most common feature of late-stage Borrelia burgdorferi infection, usually beginning months after the initial bite. In some, earlier phases are asymptomatic and arthritis is the presenting manifestation. Patients with Lyme arthritis have intermittent or persistent attacks of joint swelling and pain in 1 or a few large joints. Serologic testing is the mainstay of diagnosis. Synovial fluid polymerase chain reaction for B burgdorferi DNA is often positive before treatment, but is not a reliable marker of spirochetal eradication after therapy. This article reviews the clinical manifestations, diagnosis, and management of Lyme arthritis.

  12. Clinical management of septic arthritis in cattle.

    PubMed

    Desrochers, André; Francoz, David

    2014-03-01

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

  13. 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

  14. Crystal identification of synovial fluid aspiration by polarized light microscopy. An online test suggesting that our traditional rheumatologic competence needs renewed attention and training.

    PubMed

    Berendsen, D; Neogi, T; Taylor, W J; Dalbeth, N; Jansen, T L

    2017-03-01

    Testing a reading exercise for identification of several typical crystal such as the negatively birefringent needle-shaped crystals that are under polarized light microscopy is the gold standard for diagnosing gout. The objective of this study was to assess current performance of crystal identification by professionals involved in examining synovial fluid in routine care. Rheumatologists, trainees, lab technicians, and other physicians with an interest in crystal arthritis completed an online test. The test consisted of 30 images: 8 monosodium urate (MSU) crystals, 5 calcium pyrophosphate (CPP), 4 cholesterol, 2 depot methylprednisolone, 2 calcium oxalate, 2 rice bodies, 1 hydroxyapatite, 1 liquid lipid, 1 fibrin, 1 Charcot-Leyden, and 5 different artifacts. Of the 22 non-MSU slides, a subset of 8 was pre-designated that were thought to be clinically important to be identified as non-MSU. The primary outcome was defined as the correct identification of all eight MSU slides plus the identification of all eight pre-defined non-MSU slides as non-MSU. The online test was completed by 110 participants. The primary outcome was achieved by 39%. Correct identification of all MSU images was achieved by 81%, correct identification of all 8 pre-defined non-MSU, CPP images, and all 22 non-MSU images as non-MSU by 68, 68, and 23%, respectively. MSU crystals were well identified, but incorrect identification of non-MSU crystals occurred frequently. This study suggests that there is room for improvement regarding crystal identification of particularly CPP and other non-MSU crystals even in this highly motivated group.

  15. Growth of monosodium urate monohydrate crystals: effect of cartilage and synovial fluid components on in vitro growth rates.

    PubMed Central

    Burt, H M; Dutt, Y C

    1986-01-01

    The effects of cartilage and synovial fluid components such as proteoglycans, chondroitin sulphate, hyaluronic acid, phospholipids, and albumin on the growth kinetics of monosodium urate monohydrate (MSUM) crystals were investigated. MSUM seed crystals were added to supersaturated sodium urate solutions, and the rate of decrease in the concentration of growth medium was used as a measure of the growth rate. A second order dependence of growth rate on supersaturation was found, and growth rate constants were determined with an integrated form of the growth equation. The additives, hyaluronic acid, proteoglycan monomer and aggregate, and phosphatidylserine, had no significant effect on the growth rate constant. Chondroitin sulphate and phosphatidylcholine increased the growth rate constant, possibly by promoting further nucleation in the growth medium. Albumin significantly inhibited MSUM crystallisation. The possible implications of these findings on in vivo MSUM crystallisation are discussed. PMID:3098195

  16. Role of viscosupplementation in osteo-arthritis of knee joint.

    PubMed

    Chandra, Rajesh; Mahajan, Sumit

    2013-05-01

    Osteo-arthritis is the chronic degenerative disease associated with joint pain and loss of joint function. It is caused by 'wear and tear' on a joint. Knee is the most commonly Involved joint. Disease is so crippling that patient is unable to walk independently from bed to bathroom. The major causes of osteo-arthritis are age, gender, obesity, medical condition and hereditary. The signs and symptoms of osteo-arthritis are pain, joint stiffness, joint swelling, and loss of function. No blood tests are helpful in diagnosing osteo-arthritis. Management of osteo-arthritis includes non-pharmacological, pharmacological and surgical. A relatively new procedure is viscosupplementation, in which a preparation of hyaluronic acid is injected into the knee joint. Hyaluronic acid is a naturally occurring substance found in the synovial fluid. It acts as a lubricant to enable bones to move smoothly over each other and a shock absorber for joint loads. The decrease in the elastic and viscous properties of synovial fluid in osteo-arthritis results from both a reduced molecular size and a reduced concentration of hyaluronic acid in the synovial fluid. Viscosupplementation may be a therapeutic option for individuals with osteo-arthritis of the knee. Viscosupplementation has been shown to relieve pain in many patients who cannot get relief from non-medicinal measures or analgesic drugs. This article is to know the mechanism of action, patients' selection criteria, rationale and efficacy of viscosupplimentation in the management of osteo-arthritis of knee.

  17. Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration

    PubMed Central

    Verburg, R; Flierman, R; Sont, J; Ponchel, F; van Dreunen, L; Levarht, E; Welling, M; Toes, R; Isaacs, J; van Laar, J M

    2005-01-01

    Objective: To determine clinical and immunological correlates of high dose chemotherapy (HDC) + autologous stem cell transplantation (ASCT) in patients with severe rheumatoid arthritis (RA), refractory to conventional treatment. Methods: Serial samples of peripheral blood and synovial tissue were obtained from seven patients with RA treated with HDC and autologous peripheral blood grafts enriched for CD34+ cells. Disease activity was assessed with the Disease Activity Score (DAS), serum concentrations of C reactive protein (CRP), and human immunoglobulin (HIg) scans, and the extent of immunoablation was determined by immunophenotyping of peripheral blood mononuclear cells, and immunohistochemistry and double immunofluorescence of synovium. Results: Clinical responders (n = 5) had a larger number of cells at baseline expressing CD3, CD4, CD27, CD45RA, CD45RB, and CD45RO in synovium (p<0.05), higher activity on HIg scans (p = 0.08), and a trend towards higher concentrations of CRP in serum than non-responders (n = 2). Subsequent remissions and relapses in responders paralleled reduction and re-expression, respectively, of T cell markers. A relatively increased expression of CD45RB and CD45RO on synovial CD3+ T cells was seen after HDC + ASCT. No correlations were found between DAS and changes in B cells or macrophage infiltration or synoviocytes. Conclusions: HDC + ASCT results in profound but incomplete immunoablation of both the memory and naïve T cell compartment, which is associated with longlasting clinical responses in most patients. The findings provide strong circumstantial evidence for a role of T cells in established RA, and demonstrate a role for the synovium in post-transplantation T cell reconstitution. PMID:15829573

  18. Changes of synovial fluid protein concentrations in supra-patellar bursitis patients after the injection of different molecular weights of hyaluronic acid.

    PubMed

    Chen, Carl P C; Hsu, Chih Chin; Pei, Yu-Cheng; Chen, Ruo Li; Zhou, Shaobo; Shen, Hsuan-Chen; Lin, Shih-Cherng; Tsai, Wen Chung

    2014-04-01

    Knee pain is commonly seen in orthopedic and rehabilitation outpatient clinical settings, and in the aging population. Bursitis of the knee joint, especially when the volume of the synovial fluid is large enough, can compress and distend the nearby soft tissues, causing pain in the knee joint. Out of all the bursae surrounding the knee joint, supra-patellar bursitis is most often associated with knee pain. Treatment strategies in managing supra-patellar bursitis include the aspiration of joint synovial fluid and then followed by steroid injection into the bursa. When supra-patellar bursitis is caused by degenerative disorders, the concept of viscosupplementation treatment may be effective by injecting hyaluronic acid into the bursa. However, the rheology or the changes in the concentrations of proteins (biomarkers) that are related to the development of bursitis in the synovial fluid is virtually unexplored. Therefore, this study aimed to identify the concentration changes in the synovial fluid total protein amount and individual proteins associated with supra-patellar bursitis using the Bradford protein assay and western immunoglobulin methods. A total of 20 patients were divided into two groups with 10 patients in each group. One group received the high molecular weight hyaluronic acid product of Synvisc Hylan G-F 20 and the other group received the low molecular weight hyaluronic acid product of Hya-Joint Synovial Fluid Supplement once per week injection into the bursa for a total of 3 weeks. Significant decreases in the synovial fluid total protein concentrations were observed after the second dosage of high molecular weight hyaluronic acid injections. Apolipoprotein A-I, interleukin 1 beta, alpha 1 antitrypsin, and matrix metalloproteinase 1 proteins revealed a trend of decreasing western immunoblotting band densities after hyaluronic acid injections. The decreases in apolipoprotein A-I and interleukin 1 beta protein band densities were significant in the high

  19. Magnetic resonance imaging in foals with infectious arthritis.

    PubMed

    Gaschen, Lorrie; LeRoux, Alexandre; Trichel, Jessica; Riggs, Laura; Bragulla, Herman H; Rademacher, Nathalie; Rodriguez, Daniel

    2011-01-01

    The magnetic resonance (MR) imaging findings of foals with infectious and noninfectious arthritis are described. Six foals with infectious arthritis and three foals with noninfectious arthritis were grouped based on synovial fluid analysis results and examined with radiography and MR imaging. Four out of six foals with infectious arthritis had osseous lesions in MR images indicative of osteomyelitis and only 4/19 lesions were detected on digital radiographs. The three foals with noninfectious arthritis had no osseous lesions in MR images or radiographically. Of the six joints that had osseous lesions detected with MR imaging, three had at least one lytic lesion detected radiographically. Osseous lesions in the epiphysis, metaphysis, and physis appeared in MR images as T2W, short tau inversion recovery, and proton density hyperintense foci with a hypointense halo. The same lesions appeared hyperintense in the 3D RSSG water excitation pulse sequence but lacked a surrounding hypointense halo. Most joints of foals with infectious arthritis had heterogenous signals within the synovial fluid whereas all of the nonseptic joints had homogenous synovial fluid signals. MR imaging appears to be better than radiography in the detection of osseous lesions in foals diagnosed with infectious arthritis and may be a valuable screening test for the presence of osteomyelitis.

  20. Rapid exclusion of bacterial arthritis using a glucometer.

    PubMed

    Omar, Mohamed; Reichling, Moritz; Liodakis, Emmanouil; Ettinger, Max; Guenther, Daniel; Decker, Sebastian; Krettek, Christian; Suero, Eduardo M; Mommsen, Philipp

    2017-03-01

    Bacterial arthritis is a medical emergency. However, prompt diagnosis and differentiation from non-infectious diseases are challenging. As bacterial metabolism leads to glucose reduction, measurement of synovial fluid glucose seems to be a promising diagnostic approach. The purpose of this study was to determine whether synovial fluid glucose levels could be accurately measured by using a glucometer and to evaluate its diagnostic accuracy in diagnosing bacterial arthritis compared to currently available markers. In a prospective diagnostic study, 102 consecutive patients with atraumatic joint effusion were included. Synovial fluid glucose concentrations were determined using both glucometer and automated analyzer respectively. Synovial fluid culture, crystal analysis, and synovial cell analysis were performed. Blood samples were taken for blood cultures, analyses of serum infection markers, and serum glucose. There was a high correlation between synovial fluid glucose measured by the glucometer and the automated analyzer (r (2) = 0.92). According to the receiver operating characteristic curve, a threshold of 1.4 mmol/l had a sensitivity of 100 % (95 % CI 78.2-100 %), a specificity of 92.0 % (95 % CI 84.1-96.7 %), a positive predictive value of 68.2 % (95 % CI 45.1-86.1 %), and a negative predictive value of 100 % (95 % CI 95.5-100 %). These results suggest that synovial fluid glucose concentrations could be reliably measured using a glucometer. Due to its simplicity, this test has the potential to be an adjunct in the diagnostic cascade of bacterial arthritis.

  1. 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

  2. False-negative rate of gram-stain microscopy for diagnosis of septic arthritis: suggestions for improvement.

    PubMed

    Stirling, Paul; Faroug, Radwane; 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.

  3. 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

  4. Cellular phagocytic studies in rheumatoid arthritis patients treated with levamisole.

    PubMed Central

    Wynne, K M; Dieppe, P A; Scott, J; Huskisson, E C

    1981-01-01

    A simple method is described which allows sequential monitoring of the endocytic activity of blood and synovial fluid cells from rheumatoid arthritis patients undergoing therapy with levamisole. Evidence of immediate (24 hours) and long-term (5-7 weeks) cellular phagocytic enhancement is presented. Images PMID:7259330

  5. Adverse Reactions to Metal on Polyethylene Implants: Highly destructive lesions related to elevated concentration of Cobalt and Chromium in synovial fluid.

    PubMed

    Eltit, Felipe; Assiri, Ali; Garbuz, Donald; Duncan, Clive; Masri, Bassam; Greidanus, Nelson; Bell, Robert; Sharma, Manju; Cox, Michael; Wang, Rizhi

    2017-03-07

    Adverse local tissue reactions (ALTR) are the primary cause of failure of metal on metal (MoM) hip implants, and fewer but not negligible number cases of non-modular metal on polyethylene (MoP) implants. In this study we analyzed 17 cases of MoP ALTR, and equal number of MoM, by histological observation, cobalt and chromium concentration in serum and synovial fluid and cytokine analysis in ALTR tissues. ALTRs in MoP are highly necrotic, affecting larger areas than MoM ALTRs. Degenerative changes in blood vessels' wall were seen in all MoP ALTRs. The concentration of cobalt and chromium was higher in synovial fluid but lower in serum of MoP patients compared to MoM patients. Elevated concentrations of chemokines were observed in ALTR tissues. We conclude that ALTRs in MoP systems are highly necrotizing lesions that seem to have a similar development to ALTRs in MoM. Alteration of vessels wall seems to have a role in the tissues necrosis, as well as the elevated concentration of cobalt and chromium in synovial fluid of MoP patients. Chemokines may be involved in the pathogenesis of ALTR and constitute possible diagnostic targets. This article is protected by copyright. All rights reserved.

  6. 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

  7. Modulation of Synovial Fluid-Derived Mesenchymal Stem Cells by Intra-Articular and Intraosseous Platelet Rich Plasma Administration

    PubMed Central

    Muiños-López, Emma; Sánchez, Pello; Anitua, Eduardo; Fiz, Nicolás; Aizpurua, Beatriz; Guadilla, Jorge; Padilla, Sabino; Prósper, Felipe

    2016-01-01

    The aim of this study was to evaluate the effect of intra-articular (IA) or a combination of intra-articular and intraosseous (IO) infiltration of Platelet Rich Plasma (PRP) on the cellular content of synovial fluid (SF) of osteoarthritic patients. Thirty-one patients received a single infiltration of PRP either in the IA space (n = 14) or in the IA space together with two IO infiltrations, one in the medial femoral condyle and one in the tibial plateau (n = 17). SF was collected before and after one week of the infiltration. The presence in the SF of mesenchymal stem cells (MSCs), monocytes, and lymphocytes was determined and quantified by flow cytometry. The number and identity of the MSCs were further confirmed by colony-forming and differentiation assays. PRP infiltration into the subchondral bone (SB) and the IA space induced a reduction in the population of MSCs in the SF. This reduction in MSCs was further confirmed by colony-forming (CFU-F) assay. On the contrary, IA infiltration alone did not cause variations in any of the cellular populations by flow cytometry or CFU-F assay. The SF of osteoarthritic patients contains a population of MSCs that can be modulated by PRP infiltration of the SB compartment. PMID:27818688

  8. Synovial fluid concentrations and relative potency of interleukin-1 alpha and beta in cartilage and meniscus degradation.

    PubMed

    McNulty, Amy L; Rothfusz, Nicole E; Leddy, Holly A; Guilak, Farshid

    2013-07-01

    Cartilage degeneration with osteoarthritis (OA) is believed to involve the activities of interleukin-1 (IL-1), which exists as alpha and beta isoforms. The goal of this study was to measure the concentrations of both isoforms of IL-1 in the synovial fluid of normal and spontaneously osteoarthritic porcine knees, and to test the hypothesis that physiologic concentrations of IL-1α and IL-1β exhibit different potencies in activating calcium signaling, the production of matrix metalloproteinases and nitric oxide, and the loss of proteoglycans and tissue mechanical properties in cartilage and meniscus. Median concentrations of IL-1α were 0.043 ng/ml with mild OA and 0.288 ng/ml with moderate OA, whereas IL-1β concentrations were 0.109 ng/ml with mild OA and 0.122 ng/ml with moderate OA. Both isoforms induced calcium signaling in chondrocytes and meniscal cells at all concentrations. Overall, cartilage and meniscus catabolism was significantly more sensitive to IL-1α than IL-1β at concentrations of 1 ng/ml or less, while few differences were observed between the two forms at 10 ng/ml. These data provide a range of physiologic IL-1 concentrations that can serve as a framework for the comparison of various in vitro studies, as well as providing further insight for the development of anti-cytokine therapies for OA.

  9. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:27877803

  11. 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.

  12. 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.

  13. Clinical manifestations of synovial cysts.

    PubMed

    Burt, T B; MacCarter, D K; Gelman, M I; Samuelson, C O

    1980-08-01

    Although synovial cysts are most commonly associated with rheumatoid arthritis and osteoarthritis, they may occur in many other conditions. The clinical manifestations of these cysts are numerous and may result from pressure, dissection or acute rupture. Vascular phenomena occur when popliteal cysts compress vessels, and result in venous stasis with subsequent lower extremity edema or thrombophlebitis. Rarely, popliteal cysts may cause arterial compromise with intermittent claudication. Neurological sequelae include pain, paresthesia, sensory loss, and muscle weakness or atrophy. When synovial cysts occur as mass lesions they may mimic popliteal aneurysms or hematomas, adenopathy, tumors or even inguinal hernias. Cutaneous joint fistulas, septic arthritis or osteomyelitis, and spinal cord and bladder compression are examples of other infrequent complications. Awareness of the heterogeneous manifestations of synovial cysts may enable clinicians to avoid unnecessary diagnostic studies and delay in appropriate management. Arthrography remains the definitive diagnostic procedure of choice, although ultrasound testing may be useful.

  14. Management of Arthritis and Rheumatism

    PubMed Central

    Gordon, Duncan

    1970-01-01

    The principles of successful management of the patient with arthritis depend on adequate patient education and various medical and physical therapy measures to control pain and maintain function. In many instances psychiatric and orthopaedic consultations are invaluable. The treatment of arthritis at any age, however, must depend on a precise diagnosis. This may require examination of synovial fluid including polarizing microscopy, serological studies, arthrographic procedures and an awareness of factors which may influence the level of serum uric acid. The establishment of a diagnosis alone may be insufficient for proper evaluation and the physician may be assisted by physio, occupational therapy and medical social work assessments. Imagesp37-a PMID:20468462

  15. 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

  16. 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.

  17. Effect of indomethacin on swelling, lymphocyte influx, and cartilage proteoglycan depletion in experimental arthritis.

    PubMed Central

    Pettipher, E R; Henderson, B; Edwards, J C; Higgs, G A

    1989-01-01

    The effects of indomethacin on antigen induced arthritis in rabbits have been investigated. Arthritis was induced in the knee joints of sensitised rabbits by intra-articular injection of antigen. Swelling of the joints was measured for 14 days after antigen challenge, and groups of animals were killed on days 1, 7, or 14 for collection of synovial fluids and tissues. Indomethacin (1 mg/kg, three times daily) reduced joint swelling and the prostaglandin E2 concentrations in synovial fluid. In addition, indomethacin increased the loss of proteoglycan from articular cartilage and the numbers of lymphocytes in the inflamed synovial lining. These findings suggest that the symptomatic benefits of indomethacin and related drugs in inflammatory arthritis may be achieved at the expense of significant adverse effects on joint tissues. PMID:2782971

  18. Gonococcal arthritis: a report of six cases.

    PubMed

    Fam, A; McGillivray, D; Stein, J; Little, H

    1973-02-03

    Six cases of gonococcal arthritis are described. Three presented during the initial "bacteremic stage" with polyarthralgia, fever, skin lesions and sterile synovial fluid. Two presented during the "septic joint stage" with positive synovial culture, and one presented during the "stage of residual deformity". Transient electrocardiographic changes were noted in two of the six cases. All responded to antibiotic therapy. One required additional surgical intervention.The condition is common, coinciding with the rising incidence of symptomatic and asymptomatic gonorrhea. Gonococcal infection must be considered in the differential diagnosis of migratory polyarthralgia, tenosynovitis, oligoarthritis, fever or unusual skin lesions. Criteria for diagnosis, lines of treatment and relevant literature are reviewed.

  19. Serum-synovial gradient data of normouricemic patients with history of gout and acute knee effusion.

    PubMed

    Rozin, A P; Braun-Moscovici, Y; Balbir-Gurman, A

    2006-11-01

    The etiology of arthritis episodes in normouricemic patients with gout is still unclear. We propose that the fluctuation in synovial urate level, as well as pH, ion strength, albumin, and globulin values relative to serum levels, could be involved in crystal formation. To assess serum-synovial gradient (SSG), the sera and synovial fluid (SF) of six normouricemic patients (men, age 48-79) with a history of gout (American College of Rheumatology criteria) and acute knee effusion were screened for uric acid, pH, osmolality (Osm), P/Ca, albumin, globulin, and SSG. Monosodium urate monohydrate (MSUM) crystals were determined by polarized light (PL). Infectious arthritis was ruled out via Gram staining and synovial fluid culture. Negative X-ray and PL microscopy results excluded chondrocalcinosis. Five patients (1-5) had inflammatory knee effusion (WBC >2,000/mm(3)), and one (patient 6) had noninflammatory knee effusion (600 WBC/mm(3)). MSUM crystals were found in the WBC of patient 1 only. He had tophaceous gout with normal serum uric acid levels and showed significant negative Osm and P and positive Ca SSG. Two crystal negative patients had severe negative pH SSG with alkaline synovial fluid, significant P/Ca SSG, and high positive globulin SSG, while one of them had supersaturated SF uric acid content. The other patients displayed an increased Osm and P/Ca SSG. All SSG values were five to ten times higher than the coefficient of variance for used methods. Noninflammatory SF of patient 6 does not appear to be related to active gout. The data on SSG for MSUM, pH, Osm, Alb/Glob, and P/Ca in normouricemic patients with gout history and acute knee effusion was not homogeneous. We propose that acid-base and ionic-protein gradient may lead to instability of subsaturated urate solution, thereby predisposing to MSUM deposits within synovial membrane and inducing inflammation.

  20. The composition and physicochemical properties of hyaluronic acids prepared from ox synovial fluid and from a case of mesothelioma

    PubMed Central

    Preston, B. N.; Davies, M.; Ogston, A. G.

    1965-01-01

    1. Materials containing hyaluronic acid have been prepared by filtration (Ogston & Stanier, 1950) from ox synovial fluid and from a protein-rich human mesothelioma fluid. The ox material has been deproteinized by treatment with chloroform and pentanol and by gradient elution on DEAE-Sephadex; several fractions were obtained by the latter method. These materials can be stored in solution at −20° without change of properties. The ox material contained 21% of protein; all other preparations contained less than 6% of protein. 2. The two materials have been compared by sedimentation and viscosity and shown to be closely similar. Treatment of the ox material with neuraminidase caused no change in its viscosity behaviour. 3. Information about the molecular configuration of the ox material has been obtained from measurements of light-scattering and viscosity. The results, though consistent with a highly extended configuration, are not consistent with a linear random-coil configuration. It is tentatively suggested that the structure may have some degree of branching and of cross-linking, which give it a rigidity with respect to expansion of the molecular domain that would not be possessed by a random coil. 4. The deproteinized material recovered from DEAE-Sephadex, though polydisperse, showed unchanged average molecular weight; however, the average radius of gyration was greater than before this treatment. 5. Acidification to approx. pH3 resulted in a contraction of the structure, with only a slight degree of expansion when the pH was restored to 6·8–7·0. 6. Measurements of optical rotatory dispersion qualitatively support a structure less simple than a linear random coil. 7. Colloid osmotic pressures of mixed solutions of bovine serum albumin and of hyaluronic acid prepared by filtration from ox synovial fluid have been measured. The results agree approximately with those of Laurent & Ogston (1963) but are in quantitative disagreement with the partition measurements

  1. 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

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

    PubMed

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

    2007-01-01

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

  3. Effects of Equine Joint Injury on Boundary Lubrication of Articular Cartilage by Synovial Fluid: Role of Hyaluronan

    PubMed Central

    Antonacci, Jennifer M.; Schmidt, Tannin A.; Serventi, Lisa A.; Cai, Matthew Z.; Shu, YuYu L.; Schumacher, Barbara L.; McIlwraith, C. Wayne; Sah, Robert L.

    2012-01-01

    Objective To compare equine synovial fluid (eSF) from post-injury and control joints for (1) cartilage boundary lubrication function, (2) putative boundary lubricant molecules hyaluronan (HA), proteoglycan-4 (PRG4), and surface-active phospholipids (SAPL), (3) relationships between lubrication function and composition, and (4) lubrication restoration by addition of HA. Methods eSF from normal (NL), acute injury (AI), and chronic injury (CI) joints were analyzed for boundary lubrication of normal articular cartilage as kinetic friction coefficient (μkinetic). eSF were also analyzed for HA, PRG4, and SAPL concentrations and HA molecular weight (MW) distribution. The effect of addition of HA, of different concentrations and MW, to AI- and NL-eSF samples on μkinetic was determined. Results The μkinetic of AI-eSF (0.036) was higher (+39%) than that of NL-eSF (0.026). Compared to NL-eSF, AI-eSF had a lower HA concentration (−30%) of lower MW forms, higher PRG4 concentration (+83%), and higher SAPL concentration (+144%). CI-eSF had μkinetic, HA, PRG4, and SAPL characteristics intermediate to that of AI-eSF and NL-eSF. Regression analysis revealed that μkinetic decreased with increasing HA concentration in eSF. The friction-reducing properties of HA alone improved with increasing concentration and MW. Addition of high-MW HA (4,000kDa) to AI-eSF reduced μkinetic to a value near that of NL-eSF. Conclusion In the acute post-injury stage, eSF exhibits poor boundary lubrication properties as indicated by a high μkinetic. HA of diminished concentration and MW may be the basis for this, and adding HA to deficient eSF restored lubrication function. PMID:22605527

  4. 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

  5. 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.

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

    PubMed

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

    2000-07-29

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

  7. [Arthritis and infections].

    PubMed

    Cimaz, R; Meregalli, E; Biggioggero, M; Casadei, A; Careddu, P

    2005-08-01

    Arthritis caused by infectious agents can be secondary to direct invasion of the joint space or to immune mechanisms (subsequent to or concomitant to an infection). Septic arthritis refers to a situation when bacteria can be cultured in synovial fluid. Arthritis can complicate for example meningococcemia or infection by Neisseria gonorrhoeae or Haemophilus influenzae. Reactive (postinfectious) arthritides are an important diagnostic category within a pediatric rheumatology practice. Yersinia and, less frequently, Salmonella, play an important role in postdiarrheal disorders. The arthritis that can ensue is usually oligoarticular and occurs 1-2 weeks after the enteric infection. Reiter's syndrome, rare in the pediatric age, is characterized by the triad urethritis-conjunctivitis-arthritis. Postviral arthritides can occur after a variety of viral infections, including Parvovirus B19, rubella, and others (e.g. hepatitis B, Epstein-Barr virus, chickenpox, mumps). Especially in patients with acute arthritis, the presence of preceding infections should always be investigated. Although the majority of postinfectious arthritides are self-limiting in nature and do not require specific treatment, conditions such as Lyme borreliosis and rheumatic fever can be associated with significant morbidity, and sometimes can be even lethal.

  8. IL-1β impedes the chondrogenic differentiation of synovial fluid mesenchymal stem cells in the human temporomandibular joint

    PubMed Central

    Liu, Wenjing; Sun, Yangpeng; He, Yiqing; Zhang, Hong; Zheng, Youhua; Yao, Yu; Zhang, Zhiguang

    2017-01-01

    Mesenchymal stem cell-based therapy has great therapeutic potential for temporomandibular joint (TMJ) cartilage repair. However, the behavior of mesenchymal stem cells in the inflammatory milieu following their delivery remains poorly understood. Synovial fluid-derived mesenchymal stem cells (SFMSCs) are a promising resource for TMJ cartilage repair, as they are easily obtained from patients with TMJ disorders (TMD). In this study, we obtained SFMSCs from patients with TMD and expanded them in vitro; we then stimulated the cells with interleukin (IL)-8, IL-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α and IL-12p. The cells expressed CD90, CD44, CD105 and CD73, and were negative for CD45, CD34, CD11b, CD19 and HLA-DR. They could be induced to differentiate into osteogenic, chondrogenic, adipogenic and neurogenic lineages in vitro. Only the levels of IL-6 and IL-8 were upregulated significantly following stimulation with IL-8, IL-1β, IL-6, IL-10, TNF-α and IL-12p. Furthermore, IL-6 and IL-8 expression was driven mainly by IL-1β-dependent nuclear factor-κB (NF-κB) pathway activation, and was independent of IL-8, IL-6, IL-10, TNF-α and IL-12p. IL-6 and IL-8 expression was inhibited completely by treatment with the NF-κB inhibitor, BAY11-7082. SRY-box 9 (SOX9) was downregulated and matrix metalloproteinase (MMP)13 was upregulated upon chondrogenic differentiation induced in the cells also exposed to IL-1β. Sulfated glycosaminoglycan production was also reduced upon chondrogenic differentiation in the presence of IL-6, but not IL-8. Thus, IL-1β in the inflammatory milieu is crucial in regulating SFMSCs. In doing so, IL-1β impedes the chondrogenic differentiation of SFMSCs. The upregulation of IL-6 and NF-κB pathway activation also contribute to this biological behavior. The findings of our study indicate the potential adverse effects of IL-1β on the chondrogenic differentiation of SFMSCs, and may thus provide new insight into the pathogenesis of TMD. PMID

  9. Development of a synovial fluid analogue with bio-relevant rheology for wear testing of orthopaedic implants.

    PubMed

    Smith, Alan M; Fleming, Leigh; Wudebwe, Uchena; Bowen, James; Grover, Liam M

    2014-04-01

    The rheological properties of synovial fluid (SF) are crucial to the performance of joint prostheses. During the development of joint prostheses, wear tests are performed, which simulate joint movements in diluted solutions (usually between 25 and 33% v/v) of bovine serum which has very different rheological properties compared with native SF, where rheology is maintained by hyaluronan. Consequently, there is a need to develop a more suitable artificial SF. In this study, we used rheological techniques to understand SF flow properties which provided an insight into the mechanical behaviour required of a practical SF analogue. Steady-shear viscosity measurements were performed to reveal changes as a function of shear rate. To analyse the viscoelastic properties small deformation oscillatory measurements of storage modulus (G') loss modulus (G″) and complex viscosity (η(⁎)) were made. The rheological properties of the SF where compared with those of the polysaccharides sodium alginate, gellan gum and mixtures of both polymers. Initial results revealed classic shear thinning behaviour for the SF with a small Newtonian plateau at low shear rates with a gradual reduction in viscosity with increasing shear rate. Viscoelasticity measurements also showed that at low frequencies of oscillation there was a viscous response with G″ greater than G' and at higher frequencies there was an elastic response. Rheological properties were found to be similar to that of a 50:50 mix of 2% w/v high molecular weight alginate and 0.75% w/v gellan gum. Importantly, the lubricating behaviour of the serum differed significantly from the biopolymer blend over a full range of sliding velocities. The biopolymer blend was shown to lubricate the opposing surfaces more effectively. This difference was attributed to the more rapid alignment of the polysaccharide during shear when compared with the bovine albumin (the most abundant protein in serum), which typically exhibits a globular

  10. Semi-permeable membrane retention of synovial fluid lubricants hyaluronan and proteoglycan 4 for a biomimetic bioreactor.

    PubMed

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

    2010-05-01

    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 microm 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-1beta + TGF-beta1 + TNF-alpha, 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 microg/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 microm 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 approximately 20 x 10(-8) cm/s (- cells) and approximately 5 x 10(-8) cm/s (+ cells), for 90 nm membranes was approximately 35 x 10(-8) cm/s (- cells) and approximately 19 x 10(-8) cm

  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. MicroRNA-126 affects rheumatoid arthritis synovial fibroblast proliferation and apoptosis by targeting PIK3R2 and regulating PI3K-AKT signal pathway

    PubMed Central

    Deng, Jia-Xin; Zhang, Yu-Ping; Liang, Wan-Yi; Jiang, Zhen-Lan; Yu, Qing-Hong; Li, Juan

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and destruction of the joints as well as an increased risk of cardiovascular disease. RA synovial fibroblasts (RASFs) are involved in the progression of RA and release pro-inflammatory cytokines. On the other hand, microRNAs (miRs) may help control the inflammatory response of immune and non-immune cells. Therefore, our study used lentiviral expression vectors to test the effects of miR-126 overexpression on RASF proliferation and apoptosis. Luciferase experiments verified the targeting relationship between miR-126 and PIK3R2 gene. The co-transfection of anti-miR-126 and PIK3R2 siRNA to RASFs were used to identify whether PIK3R2 was directly involved in proliferation and apoptosis of miR-126-induced RASFs. Real-time polymerase chain reaction (PCR) was used to detect miR-126 and PIK3R2 expressions. MTT assay was used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis and cell cycle. Western blotting was used to detect PIK3R2, PI3K, AKT and p-AKT proteins. After Lv-miR-126 infected RASFs, the relative expression of miR-126 was significantly enhanced. MiR-126 promoted RASF proliferation and inhibited apoptosis. Levels of PIK3R2 decreased while total PI3K and p-AKT levels increased in RASFs overexpressing miR-126. Co-transfection of anti-miR-126 and PIK3R2 siRNA also increased PI3K and p-AKT levels as well as RASF proliferation and reduced apoptosis, as compared to anti-miR-126 treatment alone. Finally, luciferase reporter assays showed that miR-126 targeted PIK3R2. Our data indicate that miR-126 overexpression in RASFs inhibits PIK3R2 expression and promotes proliferation while inhibiting apoptosis. This suggests inhibiting miR-126 may yield therapeutic benefits in the treatment of RA. PMID:27729613

  13. Mediators of inflammation are down-regulated while apoptosis is up-regulated in rheumatoid arthritis synovial tissue by polymerized collagen

    PubMed Central

    FURUZAWA-CARBALLEDA, J; RODRÍQUEZ-CALDERÓN, R; DÍAZ DE LEÓN, L; ALCOCER-VARELA, J

    2002-01-01

    The aim of the study was to determine whether collagen-polyvinylpyrrolidone (collagen-PVP) modifies some proinflammatory responses in synovium cultures from rheumatoid arthritis (RA) patients. Synovium from 10 RA patients were cultured with or without 1% collagen-PVP. Tissues on the 3rd, 5th and 7th culture day were sectioned and stained by the Herovici technique. Total collagen and type I/III collagen ratios were evaluated by the Woessner micromethod and by interrupted gel electrophoresis, respectively. Collagenolytic activity was assessed by degradation of [3H]-collagen in supernatants. TIMP-1, IL-1β and TNF-α were determined in supernatants by ELISA, and the results were normalized by DNA concentration. IL-1β, TNF-α, IL-6, IL-8, MMP-1, TIMP-1, Cox-1, VCAM-1, ICAM-1 and Fas/APO95 expression was evaluated by immunohistochemistry. Apoptosis was detected by TUNEL technique. The histological analysis and electrophoresis revealed a 1·7-fold increase of type III collagen in a time-dependent fashion in collagen-PVP-treated cultures. Proinflammatory cytokines (IL-1β: 58 ± 9 versus 22 ± 10; TNF-α: 41 ± 6 versus 11 ± 3; IL-8: 59 ± 12 versus 29 ± 9; treated versus untreated), adhesion molecule (ICAM-1: 57 ± 11 versus 29 ± 15; VCAM-1: 49 ± 7 versus 21 ± 13; treated versus untreated) as well as Cox-1 (59 ± 10 versus 20 ± 3) expression was down-regulated in RA synovium treated. Meanwhile, TIMP-1 (36 ± 7 versus 57 ± 11) and Fas expression (20 ± 10 versus 55 ± 13) and apoptosis (14 ± 3 versus 55 ± 5) were up-regulated in treated cultures compared with controls. In supernatants, the collagenolytic activity, as well as IL-1β and TNF-α, levels were all down-regulated in treated cultures (two, three, fourfold, respectively). The addition of collagen-PVP to synovium-induced down-modulation of some inflammatory parameters and an increase in apoptosis of synovial cells. Perhaps this mechanism could contribute to inhibit outgrowth of pannus formation and to

  14. VLA-4-dependent and -independent pathways in cell contact-induced proinflammatory cytokine production by synovial nurse-like cells from rheumatoid arthritis patients.

    PubMed

    Takeuchi, Eiji; Tanaka, Toshiyuki; Umemoto, Eiji; Tomita, Tetsuya; Shi, Kenrin; Takahi, Koichiro; Suzuki, Ryuji; Ochi, Takahiro; Miyasaka, Masayuki

    2002-01-01

    Nurse-like stromal cell lines from the synovial tissue of patients with rheumatoid arthritis (RA-SNC) produce, on coculture with lymphocytes, large amounts of proinflammatory cytokines. In the present paper, we analyze the molecular events necessary for the induction of cytokine release from RA-SNC cells, and particularly the roles played by cell adhesion and the transmigration (also known as pseudoemperipolesis) of lymphocytes. For this purpose, the effects of various mAbs on the binding and transmigration of a human B-cell line, MC/car, were examined using a cloned RA-SNC line, RA-SNC77. To analyze the role of lymphocyte binding and transmigration on upregulated cytokine production by the RA-SNC77 cells, we used C3 exoenzyme-treated MC/car cells, which could bind to RA-SNC77 cells but could not transmigrate. Treatment with anti-CD29 or anti-CD49d mAb significantly reduced binding and transmigration of the MC/car cells. In contrast, the neutralizing anti-CD106/vascular cell adhesion molecule 1 mAb did not show any inhibitory effect. Likewise, none of the neutralizing mAbs against CD11a, CD18, CD44, CD49e, or CD54 showed significant effects. Binding of C3-treated or untreated MC/car cells to RA-SNC77 cells induced comparable levels of IL-6 and IL-8 production. In addition, the enhanced cytokine production by RA-SNC77 cells required direct lymphocyte contact via a very late antigen-4 (VLA-4)-independent adhesion pathway. These results indicate that, although both the VLA-4-dependent/vascular cell adhesion molecule 1-independent and the VLA4-independent adhesion pathways are involved in MC/car binding and subsequent transmigration, only the VLA4-independent adhesion pathway is necessary and sufficient for the enhanced proinflammatory cytokine production by RA-SNC77 cells. The transmigration process, which is dependent on Rho-GTPase, is not a prerequisite for this phenomenon.

  15. Macrophages in Synovial Inflammation

    PubMed Central

    Kennedy, Aisling; Fearon, Ursula; Veale, Douglas J.; Godson, Catherine

    2011-01-01

    Synovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage–pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA). There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished. Here we will briefly review our current understanding of macrophages and macrophage polarization in RA as well as the elements implicated in controlling polarization, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype, and may represent a novel therapeutic paradigm. PMID:22566842

  16. Arthritis

    MedlinePlus

    ... two bones meet, such as your elbow or knee. Over time, a swollen joint can become severely damaged. Some kinds of arthritis can also cause problems in your organs, such as your eyes or skin. Types of arthritis include Osteoarthritis is the most common type of arthritis. It's ...

  17. Synovial Fluid Analysis

    MedlinePlus

    PLEASE NOTE: Your web browser does not have JavaScript enabled. Unless you enable Javascript , your ability to navigate and access the features of this website will be limited. ... Proceeds from website advertising help sustain Lab Tests Online. AACC is a not-for-profit organization and does not endorse non-AACC products and services. Advertising & Sponsorship: ...

  18. First sternocostal degenerative arthritis with intrarticular fluid collection. A case report.

    PubMed

    Chalazonitis, Athanasios N; Condilis, Nicolas; Tilentzoglou, Anastasia C; Pontikis, John; Tzovara, Joannie

    2006-01-01

    A rare case with clinical condition of first sternocostal degenerative arthritis with intra-articular fluid collection that developed after long-lasting intense exercise (weight-lifting) for twenty years is reported. Imaging findings and differential diagnoses of the case are presented.

  19. Quantification of macrophage cell surface molecules in rheumatoid arthritis.

    PubMed Central

    Hessian, P A; Highton, J; Palmer, D G

    1989-01-01

    The response of macrophages to stimulation by interferon-gamma (IFN-gamma) in vitro is characterized by an increase in the cell surface expression of MHC class II HLA-DR antigen (HLA-DR) and the high-affinity Fc-receptor for immunoglobulin G (FcRI) while the expression of the C3b-receptor (CR1) is reduced. Based on these observations, we have examined further the possibility that IFN-gamma may modulate the activation of mononuclear phagocytes (Mph) in patients with rheumatoid arthritis (RA). As reported by others, we found low levels of IFN-gamma in the synovial fluid of these patients (less than 0.3 IU/ml using radioimmunoassay). As an alternative means of establishing whether Mph are influenced by levels of IFN-gamma too low to measure directly, we have quantified the expression of membrane associated HLA-DR, FcRI and CR1 on cell populations isolated from synovial fluid and peripheral blood. The expression of these molecules by Mph is known to be influenced by IFN-gamma. We found that Mph isolated from the synovial fluid of patients with RA showed a significantly increased HLA-DR expression. Significantly less CR1 was associated with the synovial fluid Mph than with peripheral blood monocytes. However the expression of the FcRI by the synovial fluid Mph and peripheral blood monocyte populations was similar. The quantitative changes in HLA-DR and CR1 expression by synovial fluid Mph (but not those of FcRI) were consistent with those seen following IFN-gamma activation of monocytes in vitro. While these results indicate that IFN-gamma may have a role in activating the Mph present in synovial fluid, the apparent independent regulation of FcRI observed suggests other mediators may also be involved. PMID:2527651

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

    PubMed

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

    2015-06-01

    Septic arthritis and gout are major diseases that should be suspected in patients with acute monoarthritis. These two diseases are clinically similar and often indistinguishable without the help of synovial fluid analysis. Recently, a novel diagnostic rule for gout without synovial fluid analysis was developed and showed relevant performances. This study aimed to determine whether this diagnostic rule could perform well in distinguishing gout from septic arthritis. The diagnostic rule comprises 7 clinical and laboratory variables, each of which is given a specified score. The probability of gout is classified into 3 groups according to the sum of the scores: high (≥ 8), intermediate (> 4 to < 8) and low probability (≤ 4). In this retrospective study, we applied this diagnostic rule to 136 patients who presented as acute monoarthritis and were subsequently diagnosed as acute gout (n = 82) and septic arthritis (n = 54) based on synovial fluid analysis. The mean sum of scores of acute gout patients was significantly higher than that of those with septic arthritis (8.6 ± 0.2 vs. 3.6 ± 0.32, P < 0.001). Patients with acute gout had significantly more 'high', and less 'low' probabilities compared to those with septic arthritis (Eta[η]: 0.776). The prevalence of acute gouty arthritis, as confirmed by the presence of monosodium crystal, was 95.5% (61/64), 57.5% (19/33), and 5.1% (2/39) in high, intermediate and low probability group, respectively. The recently introduced diagnostic rule properly discriminates acute gout from septic arthritis. It may help physicians diagnose gout in cases difficult to be differentiated from septic arthritis.

  1. 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.

  2. Acute septic arthritis.

    PubMed

    Shirtliff, Mark E; Mader, Jon T

    2002-10-01

    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.

  3. Effects of intra-articularly administered endotoxin on clinical signs of disease and synovial fluid tumor necrosis factor, interleukin 6, and prostaglandin E2 values in horses.

    PubMed

    Hawkins, D L; MacKay, R J; Gum, G G; Colahan, P T; Meyer, J C

    1993-03-01

    In each of 4 horses, sterile synovitis was induced by intra-articular injection of 3 micrograms of Escherichia coli endotoxin (lipopolysaccharide, LPS) into one antebrachiocarpal joint; an equal volume (2 ml) of phosphate-buffered saline solution (PBSS) was injected into the opposite, control carpus. Blood and 1.5 ml of synovial fluid were obtained at postinjection hours (PIH) 0, 2, 4, 8, 12, 18, 42, 66, and 144. Synovial fluid sample collection was accomplished by use of an indwelling, intra-articular catheter through PIH 12, and by arthrocentesis subsequently. Joint fluid samples were analyzed for cell counts, protein concentration, cytologic variables, and tumor necrosis factor (TNF), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) values. Tumor necrosis factor and IL-6 activities and WBC count were also measured in blood. To monitor local inflammation, skin temperature of each carpus was imaged, using a thermographic scanner prior to each sample collection time. Horses had minimal systemic effects. Mean (+/- SEM) rectal temperature increased significantly to 39.02 +/- 0.15 C only at PIH 18 after intra-articular injection of LPS. One horse had signs of mild depression from PIH 7 to 18, but its vital signs did not change appreciably. Each horse had mild signs of discomfort in the LPS-injected limb from PIH 1 to 3 until PIH 8 to 10. Mean peak surface temperature of the LPS-injected carpi was significantly higher than that of control carpi from PIH 8 to 144 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. 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.

  5. 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

  6. Mycoplasma fermentans, but not M penetrans, detected by PCR assays in synovium from patients with rheumatoid arthritis and other rheumatic disorders.

    PubMed Central

    Schaeverbeke, T; Gilroy, C B; Bébéar, C; Dehais, J; Taylor-Robinson, D

    1996-01-01

    AIM/BACKGROUND: Mycoplasmas, especially Mycoplasma fermentans, were suggested more than 20 years ago as a possible cause of rheumatoid arthritis but this hypothesis was never substantiated. In view of the superior sensitivity of the polymerase chain reaction (PCR) assay over culture, the aim was to use this method to seek M fermentans and M penetrans in synovial samples from patients with various arthritides. METHODS: Synovial fluid samples (n = 154) and synovial biopsy specimens (n = 20) from 133 patients with various rheumatic disorders were stored at -80 degrees C for between one and 40 months. Aliquots (500 microliters) of the synovial fluid samples were centrifuged and the deposit, and also the synovial biopsy specimens (approximately 1 g) were placed in lysis buffer with proteinase K for DNA extraction. The DNA was tested by using a semi-nested PCR assay for M fermentans and a single-round PCR for M penetrans. RESULTS: M fermentans was detected in the joints of eight (21%) of 38 patients with rheumatoid arthritis, two (20%) of 10 patients with spondyloarthropathy with peripheral arthritis, one (20%) of five patients with psoriatic arthritis, and four (13%) of 31 patients with unclassified arthritis. M fermentans was not found in the joints of the seven patients with reactive arthritis, the 29 with osteoarthritis or post-traumatic hydrarthrosis, the nine with gouty arthritis, nor the four with chronic juvenile arthritis. M penetrans was not detected in any sample. CONCLUSIONS: These findings show that the presence of M fermentans in the joint is associated with inflammatory rheumatic disorders of unknown cause, including rheumatoid arthritis. However, whether this organism triggers or perpetuates disease of behaves as a passenger remains conjectural. PMID:8943749

  7. Arthroplasty in veterans: Analysis of cartilage, bone, serum, and synovial fluid reveals differences and similarities in osteoarthritis with and without comorbid diabetes

    PubMed Central

    Oren, Trevor W.; Botolin, Sergiu; Williams, Allison; Bucknell, Allan; King, Karen B.

    2015-01-01

    Osteoarthritis patients with diabetes who receive total knee arthroplasty are more vulnerable to complications, including aseptic loosening and need for revision surgery. To elucidate mechanisms related to arthroplasty failure in diabetes, we examined serum and synovial fluid markers as well as collagen crosslinks in bone and cartilage of 20 patients (10 with diabetes, 10 controls without) undergoing this procedure. Hemoglobin A1c, body mass index, bone alkaline phosphatase, leptin, osteocalcin, and pyridinium were analyzed along with tissue content of the crosslinks hydroxylysylpyridinoline, lysylpyridinoline, and pentosidine. Pentosidine levels in tissue specimens from diabetic subjects were higher than in control subjects. Osteocalcin levels negatively correlated with hydroxylysylpyridinoline levels in cartilage. Osteocalcin levels also negatively correlated with pentosidine levels in cartilage, but only in subjects with diabetes. This study suggests potential metabolic mechanisms for arthroplasty failure in patients with diabetes. PMID:22234664

  8. Glucosamine binding to proteins in plasma and synovial fluid and blood cell/plasma partitioning in mouse and man in vitro.

    PubMed

    Persiani, Stefano; Matthews, Anne; Larger, Patrice; Hall, Michael; Rotini, Roberto; Trisolino, Giovanni; Antonioli, Diego; Zaccarelli, Lorenzo; Rovati, Lucio C

    2009-01-01

    Protein binding of [14C]glucosamine (400, 1000 and 4000 ng/ml) was evaluated in human and mouse plasma and in human synovial fluid. Blood cell/plasma partitioning in human and mouse was also determined. There was no measurable protein binding of [14C]glucosamine. Its association with human and mouse blood cells ranged from 43-47% and from 27-29%, respectively. Therefore, the unbound (pharmacologically active) fraction of glucosamine in plasma and at the site of action (the joint) is the same. Protein binding displacement drug-drug interactions are unlikely during the clinical use of crystalline glucosamine sulfate. No corrections are needed, either for unbound fraction when comparing human and mouse pharmacokinetic data or for blood cell/plasma partitioning to assess glucosamine total blood clearance from plasma data in these two species.

  9. Donor-Matched Comparison of Chondrogenic Potential of Equine Bone Marrow- and Synovial Fluid-Derived Mesenchymal Stem Cells: Implications for Cartilage Tissue Regeneration

    PubMed Central

    Zayed, Mohammed; Caniglia, Christopher; Misk, Nabil; Dhar, Madhu S.

    2017-01-01

    Mesenchymal stem cells (MSCs) have been demonstrated to be useful for cartilage tissue regeneration. Bone marrow (BM) and synovial fluid (SF) are promising sources for MSCs to be used in cartilage regeneration. In order to improve the clinical outcomes, it is recommended that prior to clinical use, the cellular properties and, specifically, their chondrogenic potential must be investigated. The purpose of this study is to compare and better understand the in vitro chondrogenic potential of equine bone marrow-derived mesenchymal stem cells (BMMSCs) and synovial fluid-derived mesenchymal stem cells (SFMSCs) populated from the same equine donor. BM- and SF-derived MSCs cultures were generated from five equine donors, and the MSCs were evaluated in vitro for their morphology, proliferation, trilineage differentiation, and immunophenotyping. Differences in their chondrogenic potentials were further evaluated quantitatively using glycosaminoglycan (GAG) content and via immunofluorescence of chondrogenic differentiation protein markers, SRY-type HMG box9, Aggrecan, and collagen II. The BMMSCs and SFMSCs were similar in cellular morphology, viability, and immunophenotype, but, varied in their chondrogenic potential, and expression of the key chondrogenic proteins. The SFMSCs exhibited a significant increase in GAG content compared to the BMMSCs (P < 0.0001) in three donors, suggesting increased levels of chondrogenesis. The expression of the key chondrogenic proteins correlated positively with the GAG content, suggesting that the differentiation process is dependent on the expression of the target proteins in these three donors. Our findings suggest that even though SFMSCs were hypothesized to be more chondrogenic relative to BMMSCs, there was considerable donor-to-donor variation in the primary cultures of MSCs which can significantly affect their downstream application. PMID:28149840

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

    PubMed

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

    2014-01-01

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

  11. Arthritis

    MedlinePlus

    ... joints Infection, most often by bacteria or virus Crystals such as uric acid or calcium pyrophosphate dihydrate ... common types of inflammatory arthritis include: Ankylosing ... calcium pyrophosphate deposition disease Juvenile rheumatoid ...

  12. What do measurements of molecular biomarkers in different body fluids really tell us?

    PubMed

    Poole, A Robin

    2011-04-27

    Molecular or biochemical biomarkers of joint metabolism offer promise in helping us understand joint pathology, its detection and treatment. But they have often been studied alone and in only one body fluid. Although the synovial joint is usually the focus of most arthritis pathology, it is often difficult, for a variety of reasons, to obtain synovial fluid that should best reflect changes in biomarkers related to pathology. It is therefore very important to see whether analyses of more readily obtainable sera and urine also reflect changes in synovial fluid. Catterall and colleagues, in a paper in Arthritis Research & Therapy that examines very early biomarker changes following joint injury, provide us with some insights into these important questions. As the study was very small and examined very early changes following joint injury, prior to onset of any recognisable pathology, we look forward to future larger biomarker studies of this kind in patients with clinically defined arthritic changes to which we can relate biomarker data.

  13. Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r. spectroscopy.

    PubMed

    Grootveld, M; Henderson, E B; Farrell, A; Blake, D R; Parkes, H G; Haycock, P

    1991-01-15

    Proton Hahn spin-echo n.m.r. spectroscopy was employed to detect abnormal metabolites present in rheumatoid synovial fluid that are derived from the deleterious generation of reactive oxygen radical species during exercise of the inflamed rheumatoid joint. A resonance attributable to a low-molecular-mass N-acetylglucosamine-containing oligosaccharide formed by the oxygen-radical-mediated depolymerization of synovial-fluid hyaluronate was clearly demonstrable when subjects with inflammatory joint disease were exercised. Moreover, formate, which may be derived from the attack of OH.radical on synovial-fluid carbohydrates, was also readily detectable in these samples. gamma-Radiolysis of rheumatoid synovial fluid samples and aqueous solutions of hyaluronate also gave rise to the production of the low-molecular-mass hyaluronate-derived oligosaccharide species and markedly elevated concentrations of (non-protein-bound) formate in the biological fluids. As expected, corresponding spectra of gamma-irradiated blood serum samples obtained from normal volunteers did not contain the signal attributable to the low-molecular-mass oligosaccharide species, but the formate resonance (barely detectable in non-irradiated normal serum samples) became clearly visible. Additionally, a curious increase in the effective concentration of non-protein-bound low-molecular-mass metabolites such as acetate, citrate, lactate and glutamine was observed after gamma-radiolysis of all biological fluids studied. The hyaluronate-derived low-molecular-mass oligosaccharide species and formate are suggested as novel markers of reactive oxygen radical activity in the inflamed rheumatoid joint during exercise-induced hypoxic/reperfusion injury.

  14. Brucella arthritis: a study of 96 cases in Kuwait.

    PubMed Central

    Khateeb, M I; Araj, G F; Majeed, S A; Lulu, A R

    1990-01-01

    Of 400 patients with brucellosis, 104 (26%) had arthritis, of whom 96 could be followed up. The systemic disease in the 96 patients was acute in 54 (56%), subacute in 24 (25%), and chronic in 18 (19%). The main presenting symptoms were joint pain, fever, sweating, and easy fatigability. The joints most commonly affected were the sacroiliac joint (26%) and knee (25%) followed by hip (18%) and spine (8%). There was no particular pattern of joint affection in relation to age. Joint effusion occurred in 32/104 (30%) of cases, predominantly (94%) in the acute group. Culture of synovial fluid was negative in all, and analysis of synovial fluid for cellular profile, glucose, and protein content was not particularly helpful in diagnosis. Plain radiographs did not show major pathological changes. Among the laboratory tests, including haematological and liver function tests, the brucella enzyme linked immunosorbent assay (ELISA) was the most reliable in the diagnosis of disease, using serum and synovial fluid specimens. Treatment with a combination of streptomycin plus tetracyclines or rifampicin resulted in an excellent cure rate and resolution of arthritis without sequelae or mortality. Thus brucellosis should be considered in the differential diagnosis of arthritis, especially in areas in which the disease is endemic. PMID:2270973

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

    PubMed

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

    2014-08-01

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

  16. 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.

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

    PubMed

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

    2011-10-01

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

  18. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production.

    PubMed

    Boilard, Eric; Nigrovic, Peter A; Larabee, Katherine; Watts, Gerald F M; Coblyn, Jonathan S; Weinblatt, Michael E; Massarotti, Elena M; Remold-O'Donnell, Eileen; Farndale, Richard W; Ware, Jerry; Lee, David M

    2010-01-29

    In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles--submicrometer vesicles elaborated by activated platelets--in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases.

  19. Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production

    PubMed Central

    Boilard, Eric; Nigrovic, Peter A.; Larabee, Katherine; Watts, Gerald F. M.; Coblyn, Jonathan S.; Weinblatt, Michael E.; Massarotti, Elena M.; Remold-O'Donnell, Eileen; Farndale, Richard W.; Ware, Jerry; Lee, David M.

    2010-01-01

    In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles—submicrometer vesicles elaborated by activated platelets—in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases. PMID:20110505

  20. The role of T cell interleukin-17 in conducting destructive arthritis: lessons from animal models

    PubMed Central

    Lubberts, Erik; Koenders, Marije I; van den Berg, Wim B

    2005-01-01

    Interleukin-17 (IL-17) is a T cell cytokine spontaneously produced by cultures of rheumatoid arthritis (RA) synovial membranes. High levels have been detected in the synovial fluid of patients with RA. The trigger for IL-17 is not fully identified; however, IL-23 promotes the production of IL-17 and a strong correlation between IL-15 and IL-17 levels in synovial fluid has been observed. IL-17 is a potent inducer of various cytokines such as tumor necrosis factor (TNF)-α, IL-1, and receptor activator of NF-κB ligand (RANKL). Additive or even synergistic effects with IL-1 and TNF-α in inducing cytokine expression and joint damage have been shown in vitro and in vivo. This review describes the role of IL-17 in the pathogenesis of destructive arthritis with a major focus on studies in vivo in arthritis models. From these studies in vivo it can be concluded that IL-17 becomes significant when T cells are a major element of the arthritis process. Moreover, IL-17 has the capacity to induce joint destruction in an IL-1-independent manner and can bypass TNF-dependent arthritis. Anti-IL-17 cytokine therapy is of interest as an additional new anti-rheumatic strategy for RA, in particular in situations in which elevated IL-17 might attenuate the response to anti-TNF/anti-IL-1 therapy. PMID:15642151

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

    PubMed

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

    2006-07-01

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

  2. Clinical and histopathological characterization of a large animal (ovine) model of collagen-induced arthritis.

    PubMed

    Abdalmula, A; Washington, E A; House, J V; Dooley, L M; Blacklaws, B A; Ghosh, P; Bailey, S R; Kimpton, W G

    2014-05-15

    Collagen induced arthritis (CIA) is the most studied and used rheumatoid arthritis (RA) model in animals, as it shares many pathological and immunological features of the human disease. The aim of this study was to characterize clinical and immunological aspects of the ovine CIA model, and develop lameness and histopathological scoring systems, in order to validate this model for use in therapeutic trials. Sheep were sensitized to bovine type II collagen (BCII), arthritis was induced by injection of bovine collagen type II into the hock joint and the response was followed for two weeks. Clinical signs of lameness and swelling were evident in all sheep and gross thickening of the synovium surrounding the tibiotarsal joint and erosion on the cartilage surface in the arthritic joints. Leucocyte cell counts were increased in synovial fluid and there was synovial hyperplasia, thickening of the intimal layer, inflammation and marked angiogenesis in the synovial tissue. There was a large influx of monocytes and lymphocytes into the synovial tissue, and increased expression of TNF-α and IL-1β in arthritic intima, angiogenesis and upregulation of VCAM-1. CIA in sheep appears to be an excellent large animal model of RA and has the potential for testing biological therapeutics for the treatment of rheumatoid arthritis.

  3. Rapid diagnosis of septic arthritis by quantitative analysis of joint fluid lactic acid with a monotest lactate kit.

    PubMed

    Brook, I; Controni, G

    1978-12-01

    The Monotest Lactate Kit (MLT) was compared with gas-liquid chromatography (GLC) for the rapid detection of septic arthritis. A total of 36 joint fluids were tested. Specimens were obtained from patients with septic arthritis (17 cases), inflammatory arthritis (18 cases), and degenerative arthritis (1 case). Specimens from 15 patients with bacterial arthritis had lactate levels above 65 mg/dl (mean, 318 mg/dl with the GLC method and 378 mg/dl with the MLT method). Three specimens from patients with gonococcal arthritis had levels that were not above 30 mg/dl (mean, 21 mg/dl with either the GLC or the MLT methods). Patients with inflammatory or degenerative disease yielded levels lower than 65 mg/dl (mean, 48 mg/dl with the GLC method and 46 mg/dl with the MLT method). Both methods proved to be equallly reliable in detecting septic arthritis, except for the gonococcal cases. Both methods are fast and easily adaptable to clinical laboratories; however, MLT was more definitive when quantitation was needed, required less fluid per speciment, and could be readily done at the bedside.

  4. 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.

  5. Quantification of tumor necrosis factor-α and matrix metalloproteinases-3 in synovial fluid by a fiber-optic particle plasmon resonance sensor.

    PubMed

    Huang, Yi-Ching; Chiang, Chang-Yue; Li, Cheng-Hen; Chang, Ting-Chou; Chiang, Chung-Sheng; Chau, Lai-Kwan; Huang, Kuo-Wei; Wu, Chin-Wei; Wang, Shau-Chun; Lyu, Shaw-Ruey

    2013-08-21

    The availability of techniques for sensitive detection of early stage osteoarthritis is critical for improving patient health. This study illustrates the feasibility of a fiber-optic particle plasmon resonance (FOPPR) sensor with gold nanoparticles on the unclad region of optical fiber probes for analysis of osteoarthritis biomarkers, tumor necrosis factor-α (TNF-α) and matrix metalloproteinases-3 (MMP-3). Results show that the sensor can achieve a refractive index resolution of 5.18 × 10⁻⁷ RIU and limits of detection for TNF-α and MMP-3 as low as 8.22 pg ml⁻¹ (0.48 pM) and 34.3 pg ml⁻¹ (1.56 pM), respectively. Additionally, the FOPPR sensor shows a good correlation in determining TNF-α and MMP-3 in synovial fluid with the clinically accepted enzyme-linked immunosorbent assay (ELISA) method. Finally, given the FOPPR sensor's nature of being low-cost, label-free, highly sensitive, real-time, simple-to-operate, the FOPPR sensor could offer potential to monitor biomarkers of various diseases, and provide an ideal technical tool for point-of-care diagnostics.

  6. Detection and investigation of the molecular nature of low-molecular-mass copper ions in isolated rheumatoid knee-joint synovial fluid.

    PubMed

    Naughton, D P; Knappitt, J; Fairburn, K; Gaffney, K; Blake, D R; Grootveld, M

    1995-03-20

    Low-molecular-mass copper(II) species have been detected and quantified in ultrafiltrates (n = 7) of rheumatoid synovial fluid (SF) by a highly-sensitive HPLC-based assay system with the ability to determine Cu(II) concentrations of < 10(-7) mol.dm-3. High field 1H NMR spectroscopy demonstrated that addition of Cu(II)(aq.) to isolated samples of RA SF ultrafiltrates resulted in complexation by histidine > alanine > formate > threonine > lactate > tyrosine > phenylalanine, their effectiveness in this context being in the given order. CD spectra of Cu(II)-treated samples of intact SF exhibited absorption bands typical of copper(II)-albumin complexes, in addition to a band attributable to a low-molecular-mass histidinate complex (lambda min 610 nm). Since both albumin and histidine are potent radical scavengers, these results indicate that any .OH radical generated from bound copper ions will be 'site-specifically' scavenged. Hence, low-molecular-mass copper complexes with the ability to promote the generation of .OH radical which can then escape from the metal ion co-ordination sphere (and in turn, cause damage to critical biomolecules) appear to be absent from inflammatory SF.

  7. Histochemical study of the vascular endothelium of the synovial membrane of rheumatoid arthritis and osteoarthritis by Ulex europaeus agglutinin I (UEA-I).

    PubMed

    Shoda, E; Watanabe, M; Hirohata, K; Urano, Y

    1985-10-01

    The Ulex europaeus agglutinin-I binding sites were significantly more distributed on the capillary endothelium of the synovium of rheumatoid arthritis (12 of 24 cases, positive) than of osteoarthritis (2 of 14 cases, positive). The distribution was not related to that of factor VIII related antigen nor IgG or IgM.

  8. [Septic arthritis? Gonococcal infection despite negative bacterial cultures].

    PubMed

    Saur, M; Distler, O; Müller, N

    2008-09-10

    Clinical signs of acute arthritis are non-specific. An acute painfull joint with effusion of unknown origin needs to be evaluated by puncture. The analysis of the synovial fluid will enable to divide an arthritis into three categories: crystal induced, rheumatological or septic arthritis. A bacterial infection should always be suspected. Cultures from blood, synovia and Gram stain do not reliably exclude a bacterial infection. If gonococcal, mycobacterial, borrelial and non-gonococcal-infective arthritis under antibiotic therapy is suspected, direct DNA-amplification can be helpful. A disseminated gonococcal infection (DGI) must be suspected on appearance of tenosynovitis, polyarthralgia and skin lesions. The clinical picture, diagnosis and therapy of a case with DGI is discussed.

  9. Gram staining in the diagnosis of acute septic arthritis.

    PubMed

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

    2002-10-01

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

  10. 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.

  11. [The role of biomarkers in diagnostics and forecasting of effectiveness of modern therapy of rheumatoid arthritis].

    PubMed

    Aleksandrova, E N; Novikov, A A; Nasonov, E L

    2013-08-01

    The rheumatoid arthritis is one of the most severe and widespread systemic inflammatory autoimmune diseases. The modern laboratory diagnostic of rheumatoid arthritis includes detection of large spectrum of biomarkers (autoantibodies, indicators of acute phase of inflammation, cytokines, markers of activation of endothelium, subpopulations of lymphocytes, products of metabolism of bone and cartilaginous tissue, genetic markers) in blood, synovial fluid, and synovial tissue. Alongside with common techniques of immunodiagnostics, the multiplex analysis of biomarkers based on genetic, transcript and proteomic technologies is applied. The results of identification of biomarkers are an important instrument of early diagnostics, activity evaluation, severity of disease course and disease prognosis and effectiveness of applied therapy. Among biomarkers associated with rheumatoid arthritis the most clinical value have antibodies (rheumatoid factor class IgM, antibodies to citrullinized proteins) and acute phase indicators (erythrocyte sedimentation rate, C-reactive protein) which are diagnostic criteria of rheumatoid arthritis and can be used in evaluation of prognosis of this disease. On basis of multi-parametric analysis of 12 key proteins of blood serum the new index of activity of rheumatoid arthritis (Vectra DA) is developed Nowadays, the potential biomarkers are detected providing to implement immunologic monitoring and prognosis of effectiveness of therapy of rheumatoid arthritis with genetic engineering biologic preparations. The laboratory tests are developed to evaluate immunogenicity of genetic engineering biologic preparations and diagnostic of latent tuberculosis infection in patients with rheumatoid arthritis against the background of therapy with using this group of pharmaceuticals.

  12. 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.

  13. 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).

  14. Interferon Regulatory Factor 5 Promotes Inflammatory Arthritis

    PubMed Central

    Duffau, Pierre; Menn-Josephy, Hanni; Cuda, Carla M.; Dominguez, Salina; Aprahamian, Tamar R.; Watkins, Amanda A.; Yasuda, Kei; Monach, Paul; Lafyatis, Robert; Rice, Lisa M.; Haines, G. Kenneth; Gravallese, Ellen M.; Baum, Rebecca; Richez, Christophe; Perlman, Harris; Bonegio, Ramon G.; Rifkin, Ian R.

    2015-01-01

    Objective Polymorphisms in the transcription factor IRF5 are associated with an increased risk of developing RA. This study was done to determine the role of IRF5 in arthritis development. Methods K/BxN serum transfer arthritis was induced in mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis severity was evaluated. K/BxN arthritis was also induced in mice deficient in TRIF, TLR2, TLR3, TLR4 and TLR7 to determine pathways through which IRF5 might promote arthritis. In-vitro studies were performed to determine the role of IRF5 in IL-1 receptor and TLR signaling. Results Arthritis severity was reduced in IRF5-deficient, TRIF-deficient, TLR3-deficient and TLR7-deficient mice. The expression of multiple genes regulating neutrophil recruitment or function and bioactive IL-1β formation was reduced in the joints during active arthritis in IRF5-deficient mice. In vitro studies showed that TLR7 and the TRIF-dependent TLR3 pathway induce pro-inflammatory cytokine production in disease relevant cell types in an IRF5-dependent manner. Conclusion IRF5 contributes to disease pathogenesis in inflammatory arthritis. This is likely due at least in part to the role of IRF5 in mediating pro-inflammatory cytokine production downstream of TLR7 and TLR3. As TLR7 and TLR3 are both RNA-sensing TLRs, this suggests that endogenous RNA ligands present in the inflamed joint promote arthritis development. These findings may be relevant to human RA as RNA capable of activating TLR7 and TLR3 is present in synovial fluid and TLR7 and TLR3 are upregulated in the joints of RA patients. PMID:26315890

  15. Elbow Synovial Fold Syndrome

    DTIC Science & Technology

    2007-12-01

    Density MR with arrows The clinical differential diagnosis of plica syndrome includes lateral epicondylitis (aka tennis elbow ), loose bodies... Elbow Synovial Fold Syndrome Radiology Corner Elbow Synovial Fold Syndrome Guarantor: CPT Amit Sanghi, USA, MC FS Contributors: CPT Amit...the case of a 17 year old female with elbow synovial fold syndrome (aka plica synovialis). The etiology is thought to be related to repetitive

  16. 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

  17. Type II collagen fragment HELIX-II is a marker for early cartilage lesions but does not predict the progression of cartilage destruction in human knee joint synovial fluid.

    PubMed

    Wei, Xiaochun; Yin, Kun; Li, Pengcui; Wang, Huan; Ding, Juan; Duan, Wangping; Wei, Lei

    2013-07-01

    To determine whether there is a direct correlation between the concentration of type II collagen fragment HELIX-II in synovial fluid and the severity of cartilage damage at the knee joint, 83 patients who had undergone knee arthroscopy or total knee replacement were enrolled in this study (49% women, mean ± SD age 49.5 ± 19). The content of HELIX-II in the synovial fluid samples was measured by enzyme-linked immunosorbent assay (ELISA). Cartilage damage at the knee joint was classified during arthroscopy or direct surgical observation, using the Outerbridge cartilage damage scoring system. The maximum damage score was defined as the highest score among the six areas of the knee joint, and the cumulative score was defined as the sum of the scores of the six areas of the knee joint. The intra-assay and inter-assay variations of the HELIX-II ELISA were lower than 13 and 15%, respectively. The level of HELIX-II in the severely damaged cartilage groups (cumulative scores = 11-24 or maximum score = 2-4) was much higher than in the slightly damaged cartilage groups (cumulative scores = 0-10 or maximum score = 0-1). The level of HELIX-II in cartilage from severely damaged cartilage groups was significantly higher than in the slightly damaged groups, but no significant difference was detected in the level of HELIX-II among the severely damaged cartilage sub-groups. There was a significant correlation between the HELIX-II concentration in the synovial fluid and the cumulative (r = 0.807) and maximum scores (r = 0.794). Thus, elevated HELIX-II level is correlated with early cartilage lesions, but does not have the sensitivity to predict the progression of severity of cartilage damage in the knee joint.

  18. Rheumatic disease presenting as septic arthritis: a report of 10 cases.

    PubMed

    Eberst-Ledoux, Julie; Tournadre, Anne; Makarawiez, Claudie; Le Quang, Catherine; Soubrier, Martin; Dubost, Jean-Jacques

    2013-08-01

    To determine the forms and characteristics of rheumatic diseases whose initial presentation mimics septic arthritis. Retrospective study of 398 patients hospitalized between 1979 and 2005 for arthritis diagnosed and treated as septic. In 10 cases, initial presentation of a rheumatic disease was highly suggestive of septic arthritis, and the patient was treated as such. Three had rheumatoid arthritis, 3 spondyloarthropathies, 2 unclassified rheumatic diseases, 1 Wegener granulomatosis and 1 cytosteatonecrosis. Mean time to diagnosis of rheumatic arthritis was 6 months. There were 7 males and 3 females aged from 15 to 77 years. Six had fever, and 3 had leucocytosis. Average ESR was 68 mm/1 h, and C-reactive protein was above 100 mg/l in 6 patients. Five patients had radiological signs suggestive of septic arthritis. Joint fluid count was above 100,000 WBCs/mm(3) in 2/5. Synovial biopsy suggested septic arthritis in 5 out of 6. These cases of pseudoseptic arthritis were indistinguishable from true septic arthritis. Follow-up is required in septic arthritis with negative culture findings to exclude rheumatic disease.

  19. Preferential immune response to virion surface glycoproteins by caprine arthritis-encephalitis virus-infected goats.

    PubMed Central

    Johnson, G C; Barbet, A F; Klevjer-Anderson, P; McGuire, T C

    1983-01-01

    Six months after inoculation with caprine arthritis-encephalitis virus, the serum and synovial fluid of virus-infected goats had antibodies to [35S]methionine-labeled viral proteins with apparent molecular weights of 125,000, 90,000, 28,000, and 15,000. The 125,000-, 90,000-, and 15,000-molecular-weight methionine-labeled proteins were identified as virion surface glycoproteins by lactoperoxidase iodination and galactose oxidase-boro[3H]hydride reduction labeling techniques. Radioimmunoassay antibody titers to purified p28, the most abundant viral structural protein, averaged 1:182 in synovial fluid and 1:67 in serum 6 months after inoculation. High dilutions of serum and synovial fluid reacted with gp90 and gp125 electroblotted onto nitrocellulose paper from polyacrylamide gels. Anti-gp90 activity was detected at dilutions with an immunoglobulin G content of 0.02 to 11 micrograms, whereas antibody to p28, when detectable on Western blots, was present in samples with an immunoglobulin G content of 0.1 to 2 mg, representing 100- to 1,000-fold-greater titers of antibody to the surface glycoprotein. Synovial fluids often contained more anti-gp90 antibody than did sera. Immunoprecipitation of lactoperoxidase-iodinated virus confirmed the presence of high antibody titers to the two virion surface glycoproteins. Because antiviral gp90 and gp125 antibody is abundant in the synovial fluid of infected goats, it probably contributes to the high immunoglobulin G1 concentrations seen at this site 6 months after caprine arthritis-encephalitis virus infection. Images PMID:6307878

  20. Genetic and cellular evidence of decreased inflammation associated with reduced post-traumatic arthritis in MRL/MpJ mice

    PubMed Central

    Lewis, John S.; Furman, Bridgette D.; Zeitler, Evan; Huebner, Janet L.; Kraus, Virginia B.; Guilak, Farshid; Olson, Steven A.

    2013-01-01

    Objective To examine the relationship between inflammation and post-traumatic arthritis in a murine intra-articular fracture model. Methods Male C57BL/6 and MRL/MpJ “superhealer” mice received tibial plateau fractures using a previously established method. Mice were sacrificed at 0 (within 4 hours), 1, 3, 5, 7, 28 and 56 days after fracture. Synovial tissue samples were taken prior to fracture and at 0, 1, 3, 5 and 7 days to examine gene expression of pro-inflammatory cytokines using RT-PCR. Synovial fluid and serum samples were collected to measure cytokine concentrations using ELISA. Histologic analysis was used to evaluate whole joint synovitis and cartilage degradation, and immunohistochemistry to evaluate the distribution of interleukin-1 in the joint tissues from all time points. Results Compared to the C57BL/6 mice, the MRL/MpJ mice had lower intra-articular and systemic inflammation following joint injury, as evidenced by lower gene expression of TNF-α and IL-1β in synovial tissue, and lower protein levels of IL-1α and IL-1β in the synovial fluid, serum, and joint tissues. Furthermore, MRL/MpJ mice had lower gene expression of macrophage inflammatory proteins (MIPs) and macrophage derived chemokine (MDC/CCL22) in synovial tissue, and reduced acute and late-stage infiltration of synovial macrophages after joint injury. Conclusion C57BL/6 mice exhibited higher levels of inflammation than MRL/MpJ mice, which are protected from post-traumatic arthritis in this model. These data thus suggest an association between joint tissue inflammation and post-traumatic arthritis in mice. PMID:23203659

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

    PubMed Central

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

    2015-01-01

    Objectives Synovial fluid glutamate concentrations increase in arthritis. Activation of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6 (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA and KA GluRs are expressed in human arthritis, and that intra-articular NBQX (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced arthritis (AIA). Methods GluR immunohistochemistry was related to synovial inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). A single intra-articular NBQX injection was given at induction, and knee swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging, RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human primary osteoblast (HOB) activity were determined. Results AMPAR2 and KA1 immunolocalised to remodelling bone, cartilage and synovial cells in human OA and RA, and rat AIA. All arthritic tissues showed degradation and synovial inflammation. NBQX reduced GluR abundance, knee swelling (p<0.001, days 1–21), gait abnormalities (days 1–2), end-stage joint destruction (p<0.001), synovial inflammation (p<0.001), and messenger RNA expression of meniscal IL-6 (p<0.05) and whole joint cathepsin K (p<0.01). X-ray and MRI revealed fewer cartilage and bone erosions, and less inflammation after NBQX treatment. NBQX reduced HOB number and prevented mineralisation. Conclusions AMPA/KA GluRs are expressed in human OA and RA, and in AIA, where a single intra-articular injection of NBQX reduced swelling by 33%, and inflammation and degeneration scores by 34% and 27%, respectively, exceeding the efficacy of approved drugs in the same model. AMPA/KA GluR antagonists represent a potential treatment for arthritis. PMID:24130267

  2. 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

  3. Juvenile rheumatoid arthritis with rice bodies: light and electron microscopic studies.

    PubMed Central

    Wynne-Roberts, C R; Cassidy, J T

    1979-01-01

    Rice bodies obtained from a young man with juvenile rheumatoid arthritis were found by light and electron microscopy to contain cells that appeared viable. The majority of these cells closely resembled type B synovial lining cells. Type A-like cells were also seen. The cells contained few mitochondria but often much lipid and glycogen, observations which suggested a dependence on anaerobic metabolic pathways in the avascular synovial fluid environment. Cells within the rice bodies lay in a matrix of collagen fibres, fibrin, and amorphous material. The source of the collagen appeared to be the cells themselves. The relatively normal appearance of the cells suggested that they were protected from many of the inflammatory stimuli present in rheumatoid synovia. This 'reversion' towards a normal appearance suggested that the stimuli inducing chronic rheumatoid inflammation might not originate in the synovial lining. Images PMID:434952

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

    PubMed

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

    1992-05-01

    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.

  5. Proliferation of the synovial lining cell layer in suggested metal hypersensitivity.

    PubMed

    Burkandt, Andreas; Katzer, Alexander; Thaler, Karlheinz; Von Baehr, Volker; Friedrich, Reinhard E; Rüther, Wolfgang; Amling, Michael; Zustin, Jozef

    2011-01-01

    Synovial tissues in joints with prostheses display characteristic morphological changes in cases with aseptic failure, particularly macrophage infiltration. Since proliferation of the synovial lining cell layer represents a feature characteristic of autoimmune joint diseases, the possibility of morphological changes of the synovial lining cell layer in periprosthetic tissues was investigated. Synovial biopsies from five groups of morphologically well-defined lesions (osteoarthritis, rheumatoid arthritis, aseptic loosened metal-on-polyethylene and metal-on-metal arthroplasty and suggested metal hypersensitivity) were compared using a conventional staining method and immunohistochemistry. The synovial lining cell layer was substantially enlarged in both rheumatoid arthritis and cases suggestive of metal hypersensitivity. Macrophage infiltrates were apparent in rheumatoid arthritis and all specimens from retrieved hip arthroplasties. Although both synovial and subsynovial macrophages were positive for CD163 (indicating synovial M2 macrophages), the remaining fibroblast-like synoviocytes and scattered stromal fibroblasts showed a positive reaction with the D2-40 antibody (indicating fibroblast-like synoviocytes). Furthermore, in contrast to CD163-positive macrophages, the enlarged D2-40-positive fibroblast-like synoviocytes displayed cytoplasmatic tubular projections. Proliferation of the periprosthetic synovial lining cell layer occurred in cases with unexplained groin pain following metal-on-metal hip resurfacing arthroplasty, suggestive of hypersensitivity. Despite some important study limitations, the present observation adds to the evidence that metal hypersensitivity shares characteristic morphological features with autoimmune diseases of the joints.

  6. [Streptococcus equisimilis associated septic arthritis/prosthetic joint infection].

    PubMed

    Sipahi, Oğuz Reşat; Ozkören Calik, Sebnem; Pullukçu, Hüsnü; Işikgöz Taşbakan, Meltem; Arda, Bilgin; Tünger, Alper; Ulusoy, Sercan

    2008-07-01

    Group C streptococci are flora members of skin, nasopharynx, gastrointestinal and genitourinary systems. They are rare causes of human pharyngitis, arthritis, pneumonia, meningitis and bacteremia. In this report, a 71-years old male patient with Streptococcus equisimilis arthritis/prosthetic joint infection has been presented. The patient was admitted to the emergency service with the complaints of erythema, swelling and tenderness on right knee which had total knee prosthesis. Examination of synovial fluid punction sample yielded abundant amount of leukocytes (> 1000 cells/mm3). Empirical ampicillin-sulbactam (1 g q6h, parenterally) therapy was initiated. Bacteria which have been cultivated from synovial fluid specimen were identified as S. equisimilis. The isolate was found to be susceptible to penicilin, erythromycin and teicoplanin, and resistant to chloramphenicol and tetracycline. Although clinical presentation improved during the first ten days, symptoms recurred after the 10th day and the therapy was switched to teicoplanin. The recurrence was thought to be the result of antibiotic tolerence. The patient was treated successfully with teicoplanin, and no relapse or reinfection was observed during one year of follow-up. To our knowledge this is the first case of S. equisimilis arthritis reported from Turkey and first case of S. equisimilis associated prosthetic joint infection.

  7. Tryptase is a candidate autoantigen in rheumatoid arthritis.

    PubMed

    Guo, Yanyan; Wu, Qiao; Ni, Bing; Mou, Zhirong; Jiang, Qiong; Cao, Yi; Dong, Hui; Wu, Yuzhang

    2014-05-01

    Autoimmune processes have been implicated in the development of rheumatoid arthritis (RA); however, specific autoantigens that play a role in the aetiology of RA have been lacking. In this study, we found that sera from RA patients were particularly immunoreactive against the protein tryptase. Compared with osteoarthritis (OA) patients and healthy controls, RA patients had relatively higher levels of tryptase and concomitant anti-tryptase antibodies in their synovial tissues and sera. Similarly, synovial fluid from RA patients, but not from OA patients, contained antibodies that recognized tryptase in vitro. In addition, serum tryptase levels in both early and late RA patients significantly correlated with clinical indices usually used to diagnose RA, such as rheumatoid factor, Disease Activity Score using 28 joint counts and autoantibodies against cyclic citrullinated peptide. Our results identify tryptase as a candidate autoantigen involved in the pathogenesis of RA and monitoring its levels may have diagnostic and prognostic value.

  8. Glucose-6-Phosphate Isomerase (G6PI) Mediates Hypoxia-Induced Angiogenesis in Rheumatoid Arthritis

    PubMed Central

    Lu, Ying; Yu, Shan-Shan; Zong, Ming; Fan, Sha-Sha; Lu, Tian-Bao; Gong, Ru-Han; Sun, Li-Shan; Fan, Lie-Ying

    2017-01-01

    The higher level of Glucose-6-phosphate isomerase (G6PI) has been found in both synovial tissue and synovial fluid of rheumatoid arthritis (RA) patients, while the function of G6PI in RA remains unclear. Herein we found the enrichment of G6PI in microvascular endothelial cells of synovial tissue in RA patients, where a 3% O2 hypoxia environment has been identified. In order to determine the correlation between the high G6PI level and the low oxygen concentration in RA, a hypoxia condition (~3% O2) in vitro was applied to mimic the RA environment in vivo. Hypoxia promoted cellular proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and induced cell migration and angiogenic tube formation of human dermal microvascular endothelial cells (HDMECs), which were accompanied with the increased expression of G6PI and HIF-1α. Through application of G6PI loss-of-function assays, we confirmed the requirement of G6PI expression for those hypoxia-induced phenotype in RA. In addition, we demonstrated for the first time that G6PI plays key roles in regulating VEGF secretion from RASFs to regulate the hypoxia-induced angiogenesis in RA. Taken together, we demonstrated a novel pathway regulating hypoxia-induced angiogenesis in RA mediated by G6PI. PMID:28067317

  9. Treatment with recombinant Hsp72 suppresses collagen-induced arthritis in mice.

    PubMed

    Luo, Xinjing; Zuo, Xiaoxia; Mo, Xuanrong; Zhou, Yaou; Xiao, Xianzhong

    2011-10-01

    Although the level of heat shock protein (Hsp72) has been shown to be enhanced in rheumatoid arthritis (RA) synovial tissues and RA synovial fluid, it remains unclear what role extracellular Hsp72 plays in the pathogenesis of RA. This study was conducted to investigate the effects of recombinant human Hsp72 on collagen-induced arthritis (CIA) when administered therapeutically and elucidate its underlying mechanism. We demonstrated that recombinant Hsp72 significantly reduced disease severity. Hsp72-treated animals displayed significantly less cartilage and bone destruction than that in the controls. Hsp72 treatment also reduced the expression of tumor necrosis factor alpha and interleukin 6 in the sera. Furthermore, Hsp72 treatment significantly inhibited activation of nuclear factor kappa B (NF-κB) in synovial tissues of CIA mice. These findings suggest that recombinant Hsp72 effectively suppressed synovial inflammation and the development and progress of CIA, which is mediated through the reduction of production of proinflammatory cytokines and the suppression of activation of NF-κB pathway.

  10. Arthritis in the highlands of Papua New Guinea.

    PubMed

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

    1993-01-01

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

  11. Infectious Arthritis

    MedlinePlus

    ... 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.

  12. 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

  13. Evaluation of new anti-infective drugs for the treatment of infectious arthritis in adults. Infectious Diseases Society of America and the Food and Drug Administration.

    PubMed

    Norden, C; Nelson, J D; Mader, J T; Calandra, G B

    1992-11-01

    This guideline describes clinical trials of new anti-infective drugs for the treatment of septic arthritis due to bacteria other than Neisseria gonorrhoeae in adults. Septic arthritis is associated with fever and with physical findings at the affected joint. Diagnosis is established by culture of synovial fluid. Treatment includes the administration of antimicrobial drugs and drainage of the joint by needle aspiration or surgery. Multicenter, randomized comparative clinical trials that are single-, double-, or evaluator-blinded should be performed. However, an open trial of a new antimicrobial agent with historical controls is acceptable. Patients should receive treatment for at least 2-3 weeks. After 5 days of antimicrobial therapy, synovial fluid should be sterile and clinical signs and symptoms should have diminished. Patients should be followed for 2-4 weeks after completion of therapy.

  14. Inhibition of protein geranylgeranylation induces apoptosis in synovial fibroblasts.

    PubMed

    Connor, Alison M; Berger, Stuart; Narendran, Aru; Keystone, Edward C

    2006-01-01

    Statins, competitive inhibitors of hydroxymethylglutaryl-CoA reductase, have recently been shown to have a therapeutic effect in rheumatoid arthritis (RA). In RA, synovial fibroblasts in the synovial lining, are believed to be particularly important in the pathogenesis of disease because they recruit leukocytes into the synovium and secrete angiogenesis-promoting molecules and proteases that degrade extracellular matrix. In this study, we show a marked reduction in RA synovial fibroblast survival through the induction of apoptosis when the cells were cultured with statins. Simvastatin was more effective in RA synovial fibroblasts than atorvastatin, and both statins were more potent on tumor necrosis factor-alpha-induced cells. In contrast, in osteoarthritis synovial fibroblasts, neither the statin nor the activation state of the cell contributed to the efficacy of apoptosis induction. Viability of statin-treated cells could be rescued by geranylgeraniol but not by farnesol, suggesting a requirement for a geranylgeranylated protein for synovial fibroblast survival. Phase partitioning experiments confirmed that in the presence of statin, geranylgeranylated proteins are redistributed to the cytoplasm. siRNA experiments demonstrated a role for Rac1 in synovial fibroblast survival. Western blotting showed that the activated phosphorylated form of Akt, a protein previously implicated in RA synovial fibroblast survival, was decreased by about 75%. The results presented in this study lend further support to the importance of elevated pAkt levels to RA synovial fibroblast survival and suggest that statins might have a beneficial role in reducing the aberrant pAkt levels in patients with RA. The results may also partly explain the therapeutic effect of atorvastatin in patients with RA.

  15. Mast cells contribute to autoimmune inflammatory arthritis via their tryptase/heparin complexes.

    PubMed

    Shin, Kichul; Nigrovic, Peter A; Crish, James; Boilard, Eric; McNeil, H Patrick; Larabee, Katherine S; Adachi, Roberto; Gurish, Michael F; Gobezie, Reuben; Stevens, Richard L; Lee, David M

    2009-01-01

    Although mast cells (MCs) often are abundant in the synovial tissues of patients with rheumatoid arthritis, the contribution of MCs to joint inflammation and cartilage loss remains poorly understood. MC-restricted tryptase/heparin complexes have proinflammatory activity, and significant amounts of human tryptase beta (hTryptase-beta) are present in rheumatoid arthritis synovial fluid. Mouse MC protease-6 (mMCP-6) is the ortholog of hTryptase-beta, and this serine protease is abundant in the synovium of arthritic mice. We now report that C57BL/6 (B6) mice lacking their tryptase/heparin complexes have attenuated arthritic responses, with mMCP-6 as the dominant tryptase responsible for augmenting neutrophil infiltration in the K/BxN mouse serum-transfer arthritis model. While inflammation in this experimental arthritis model was not dependent on protease-activated receptor-2, it was dependent on the chemokine receptor CXCR2. In support of the latter data, exposure of synovial fibroblasts to hTryptase-beta/heparin or mMCP-6/heparin complexes resulted in expression of the neutrophil chemotactic factors CXCL1/KC, CXCL5/LIX, and CXCL8/IL-8. Our proteomics, histochemistry, and immunohistochemistry data also revealed substantial loss of cartilage-derived aggrecan proteoglycans in the arthritic joints of wild-type B6 mice but not mMCP-6-null B6 mice. These observations demonstrate the functional contribution of MC-restricted tryptase/heparin complexes in the K/BxN mouse arthritis model and connect our mouse findings with rheumatoid arthritis pathophysiology.

  16. Transient receptor potential canonical 5 (TRPC5) protects against pain and vascular inflammation in arthritis and joint inflammation

    PubMed Central

    Srivastava, Salil; Riffo-Vasquez, Yanira; Baldissera, Lineu; Thakore, Pratish; Saleque, Nurjahan; Fernandes, Elizabeth S; Walsh, David A; Brain, Susan D

    2017-01-01

    Objective Transient receptor potential canonical 5 (TRPC5) is functionally expressed on a range of cells including fibroblast-like synoviocytes, which play an important role in arthritis. A role for TRPC5 in inflammation has not been previously shown in vivo. We investigated the contribution of TRPC5 in arthritis. Methods Male wild-type and TRPC5 knockout (KO) mice were used in a complete Freund's adjuvant (CFA)-induced unilateral arthritis model, assessed over 14 days. Arthritis was determined by measurement of knee joint diameter, hindlimb weightbearing asymmetry and pain behaviour. Separate studies involved chronic pharmacological antagonism of TRPC5 channels. Synovium from human postmortem control and inflammatory arthritis samples were investigated for TRPC5 gene expression. Results At baseline, no differences were observed. CFA-induced arthritis resulted in increased synovitis in TRPC5 KO mice assessed by histology. Additionally, TRPC5 KO mice demonstrated reduced ispilateral weightbearing and nociceptive thresholds (thermal and mechanical) following CFA-induced arthritis. This was associated with increased mRNA expression of inflammatory mediators in the ipsilateral synovium and increased concentration of cytokines in synovial lavage fluid. Chronic treatment with ML204, a TRPC5 antagonist, augmented weightbearing asymmetry, secondary hyperalgesia and cytokine concentrations in the synovial lavage fluid. Synovia from human inflammatory arthritis demonstrated a reduction in TRPC5 mRNA expression. Conclusions Genetic deletion or pharmacological blockade of TRPC5 results in an enhancement in joint inflammation and hyperalgesia. Our results suggest that activation of TRPC5 may be associated with an endogenous anti-inflammatory/analgesic pathway in inflammatory joint conditions. PMID:27165180

  17. Scube regulates synovial angiogenesis-related signaling.

    PubMed

    Yang, Min; Guo, Mingyang; Hu, Yonghe; Jiang, Yong

    2013-11-01

    Angiogenesis is particularly driven in the synovial microenvironment of Rheumatoid arthritis (RA), and considered as the fundamental cause for the persistent injury and chronic damage. Therefore, exploring the pathomechanism of synovial angiogenesis may provide promising prospects for vascular-targeting treatment of RA. The noval family of Scube proteins is confirmed to overlap significantly in structure characterized by epidermal growth factor (EGF)-like domains and CUB (complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1) domain. As secreted glycoprotein and peripheral membrane protein, Scube increases its serum level in response to stimuli of inflammation and hypoxia. In rheumatoid angiogenesis-related signaling system defined by hedgehog (Hh), transforming growth factor (TGF)β and bone morphogenetic protein 2 (BMP2), Scube1 and 2 antagonize BMP2 signaling, suppressing BMP2-induced phospho-Smad1/5/8 level in vivo. Scube3 functions as an endogenous TGFβ receptor ligand, increasing Smad2/3 phosphorylation, and thus upregulates target genes involved in angiogenesis. Via obligate assistance of Scube1 and 3, Scube2 plays a center role to recruit dually lipid-modified Hh transferred from Dispatched A (DispA), increasing Hh secretion by promoting its solubility. These findings support the hypothesis that Scube may regulate synovial angiogenesis may be the ideal vascular targets for anti-rheumatic treatment of RA.

  18. Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators?

    PubMed Central

    2012-01-01

    Introduction We have taken advantage of the large screening capacity of a multiplex immunoassay to better define the respective contribution of articular versus systemic cytokines in experimental arthritis. Methods We performed a follow up (from 7 hours to 14 days) multiplex analysis of 24 cytokines in synovial fluid and sera of rats developing Antigen-Induced Arthritis (AIA) and confronted their protein level changes with molecular, biochemical, histological and clinical events occurring in the course of the disease. Results The time-scheduled findings in arthritic joints correlated with time-dependent changes of cytokine amounts in joint effusions but not with their blood levels. From seven hours after sensitization, high levels of chemokines (MCP-1, MIP1α, GRO/KC, RANTES, eotaxin) were found in synovial fluid of arthritic knees whereas perivascular infiltration occurred in the synovium; local release of inflammatory cytokines (IFNγ, IL-1β, IL-6) preceded the spreading of inflammation and resulted in progressive degradation of cartilage and bone. Finally a local overexpression of several cytokines/adipocytokines poorly described in arthritis (IL-13, IL-18, leptin) was observed. Conclusions Distinct panels of cytokines were found in arthritic fluid during AIA, and the expected effect of mediators correlated well with changes occurring in joint tissues. Moreover, multiplex analysis could be helpful to identify new pathogenic mediators and to elucidate the mechanisms supporting the efficacy of putative targeted therapies. PMID:22414623

  19. Hypoxia-inducible factor-1α and interleukin 33 form a regulatory circuit to perpetuate the inflammation in rheumatoid arthritis.

    PubMed

    Hu, Fanlei; Shi, Lianjie; Mu, Rong; Zhu, Jiaxin; Li, Yingni; Ma, Xiaoxu; Li, Chun; Jia, Rulin; Yang, Dongyue; Li, Yun; Li, Zhanguo

    2013-01-01

    Hyperplasia of synovial fibroblasts, infiltration with inflammatory cytokines, and tissue hypoxia are the major characteristics of rheumatoid arthritis (RA). Interleukin 33 (IL-33) is a newly identified inflammatory cytokine exacerbating the disease severity of RA. Hypoxia-inducible factor-1α (HIF-1α) showed increased expression in RA synovium and could regulate a number of inflammatory cytokine productions. Nevertheless, its correlation with IL-33 remains largely unknown. Here, we showed that elevated levels of IL-33 were demonstrated in RA patient synovial fluids, with upregulated expression of HIF-1α and IL-33 in the synovial fibroblasts. Knocking down HIF-1α compromised IL-33 expression in rheumatoid arthritis synovial fibroblasts (RASF), while enforcing HIF-1α expression in RASF substantially upregulated IL-33 levels. HIF-1α promoted the activation of the signalling pathways controlling IL-33 production, particularly the p38 and ERK pathways. Moreover, we showed for the first time that IL-33 in turn could induce more HIF-1α expression in RASF, thus forming a HIF-1α/IL-33 regulatory circuit that would perpetuate the inflammatory process in RA. Targeting this pathological pathway and HIF-1α may provide new therapeutic strategies for overcoming the persistent and chronic inflammatory disease.

  20. Candida lusitaniae arthritis in an intravenous drug user.

    PubMed

    Jeragh, A; Ahmad, S; Naseem, J; Khan, Z U

    2007-09-01

    A case of arthritis of the right knee caused by Candida lusitaniae in a 29-year-old intravenous drug abuser is described. The diagnosis was based on the isolation of C. lusitaniae from synovial fluid and was supported by the presence of C. lusitaniae-specific DNA and high levels of (1-3)-beta-d-glucan (122 pg ml-1) in the same specimen. While the isolate was susceptible to amphotericin B and fluconazole in vitro, treatment with amphotericin B was not very effective. The patient achieved complete cure with fluconazole therapy only after undergoing synovectomy. To the best of our knowledge, this is the first report of arthritis caused by C. lusitaniae in an intravenous drug user.

  1. 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

  2. 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.

  3. Small ruminant lentivirus-induced arthritis: clinicopathologic findings in sheep infected by a highly replicative SRLV B2 genotype.

    PubMed

    Pérez, M; Biescas, E; Reina, R; Glaria, I; Marín, B; Marquina, A; Salazar, E; Álvarez, N; de Andrés, D; Fantova, E; Badiola, J J; Amorena, B; Luján, L

    2015-01-01

    We describe the clinicopathologic features of an arthritis outbreak in sheep induced by small ruminant lentivirus (SRLV), linked to the presence of a new SRLV isolate phylogenetically assigned to caprine arthritis encephalitis virus-like subgroup B2. Thirteen SRLV seropositive Rasa Aragonesa adult ewes were selected from 5 SRLV highly infected flocks (mean seroprevalence, 90.7%) for presenting uni- or bilateral chronic arthritis in the carpal joint. A complete study was performed, including symptomatology, histopathology, immunocytochemistry, immunohistochemistry, in situ hybridization, and microbiology. The carpus was the joint almost exclusively affected, with 10 sheep (76%) showing a moderate increase in carpal joint size (diameter range, 18-20 cm; normal range, 15-16 cm) without signs of locomotion problems and with 3 ewes (23%) showing severe inflammation with marked increase in diameter (21-24 cm), pain at palpation, and abnormal standing position. Grossly, chronic proliferative arthritis was observed in affected joints characterized by an increased thickness of the synovial capsule and synovial membrane proliferation. Microscopically, synovial membrane inflammation and proliferation and hyperplasia of synoviocytes were observed. More positive cases of SLRV infection were detected by immunocytochemistry of articular fluid than of bronchoalveolar lavage fluid. Immunohistochemistry and in situ hybridization also detected positive cells in the subsynovial connective tissue, lung, mediastinal lymph node, mammary gland, and mammary lymph node. All animals were negative for the presence of Mycoplasma or other bacteria in the articular space. The present outbreak likely represents an adaptation of a caprine virus to sheep. Our results underline the importance of the arthritis induced by SRLV in sheep, a clinical form that might be underestimated.

  4. 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.

  5. Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue.

    PubMed

    Mingozzi, F; Chen, Y; Edmonson, S C; Zhou, S; Thurlings, R M; Tak, P P; High, K A; Vervoordeldonk, M J

    2013-04-01

    Antibodies against adeno-associated viral (AAV) vectors are highly prevalent in humans. Both preclinical and clinical studies showed that antibodies against AAV block transduction even at low titers, particularly when the vector is introduced into the bloodstream. Here we measured the neutralizing antibody (NAb) titer against AAV serotypes 2, 5, 6 and 8 in the serum and matched synovial fluid (SF) from rheumatoid arthritis patients. The titer in the SF was lower than that in the matched plasma samples, indicating a difference in distribution of NAb to AAV depending on the body fluid compartment. This difference was more evident for AAV2, against which higher titers were measured. Of all serotypes, anti-AAV5 antibodies were the least prevalent in both the serum and SF. We next evaluated the impact of B-cell depletion on anti-AAV antibodies in rheumatoid arthritis patients who received one or two courses of the anti-CD20 antibody rituximab as part of their disease management. A drop of NAb titer was observed in a subset of those subjects carrying NAb titers ≤1:1000; however, only in a minority of subjects titers dropped below 1:5. This work provides insights into strategies to overcome the limitation of pre-existing humoral immunity to AAV vectors.

  6. Measurement of inflammatory biomarkers in synovial tissue extracts by enzyme-linked immunosorbent assay.

    PubMed

    Rosengren, Sanna; Firestein, Gary S; Boyle, David L

    2003-11-01

    We developed methods for measuring inflammatory biomarkers (cytokines, chemokines, and metalloproteinases) in synovial biopsy specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Soluble extracts of synovial fragments were prepared with mild detergent and analyzed by enzyme-linked immunosorbent assay (ELISA) for interleukin 1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and matrix metalloproteinase 3. The optimal detergent was 0.1% Igepal CA-630, which interfered minimally with ELISA detection but extracted 80% of IL-6 from synovial tissue. Upon spiking, 81 to 107% of added biomarkers could be recovered. To determine within-tissue variability, multiple biopsy specimens from each RA synovial extract were analyzed individually. A resulting coefficient of variation of 35 to 62% indicated that six biopsy specimens per synovial extract would result in a sampling error of < or = 25%. Preliminary power analysis suggested that 8 to 15 patients per group would suffice to observe a threefold difference before and after treatment in a serial biopsy clinical study. The previously described significant differences in IL-1beta, IL-6, IL-8, and TNF-alpha levels between RA and OA could be detected, thereby validating the use of synovial extracts for biomarker analysis in arthritis. These methods allow monitoring of biomarker protein levels in synovial tissue and could potentially be applied to early-phase clinical trials to provide a preliminary estimate of drug efficacy.

  7. Kingella kingae sequence type-complex 14 arthritis in a 16-month-old child in Greece.

    PubMed

    Grivea, Ioanna N; Michoula, Aspasia N; Basmaci, Romain; Dailiana, Zoe H; Tsimitselis, George; Bonacorsi, Stéphane; Syrogiannopoulos, George A

    2015-01-01

    We describe the first case of Kingella kingae arthritis in a 16-month-old girl in Greece, which has been diagnosed by novel molecular techniques. A joint aspiration of her knee was performed before the initiation of antibiotics, as well as on the 5th and 14th day of empiric antimicrobial therapy. The synovial fluid white blood cell count decreased from 65,000 to 1500 cells/mm, but the percentage of neutrophils remained 90% in all 3 specimens. Molecular analysis of the synovial fluid specimens by real-time polymerase chain reaction and multilocus sequence typing enabled us to reveal the presence of K. kingae belonging to the international sequence type-complex 14, which persisted up to the fifth day of antibiotic therapy.

  8. [Primary meningococcal infection of the knee. A rare cause of septic arthritis].

    PubMed

    Klatte, T O; Lehmann, W; Rueger, J M

    2015-10-01

    This article presents a case of primary septic arthritis of the knee due to serogroup C Neisseria meningitidis. A 19-year-old female presented to the emergency department with a painless but swollen knee joint which had started 2 days previously and fever (38 °C). The patient reported that she suddenly felt unwell 3 days ago and developed a rush at the same time which had almost disappeared when arrived at the emergency department. The patient was admitted to hospital and an antibiotic therapy was started with sulbactam and ampicillin. Initially, incubation of synovial fluid over the next 3 days did not result in detection of any pathogens; therefore, a reactive arthritis was assumed until Neisseria meningitidis was detected in cultures of the synovial fluid. Therapy was then switched to antibiotic therapy with ceftriaxon and arthroscopic irrigation was performed. The patient quickly recovered and was discharged from hospital after 14 days. This case example shows the difficulties of the clinical and microbiological diagnostics of a primary septic meningococcal arthritis; however, the treatment is relatively easy and mostly successful compared to other forms of bacterial joint infection.

  9. Coexistent Pseudogout and Mycobacterium avium-intracellulare Septic Arthritis in a Patient with HIV and ESRD

    PubMed Central

    Wali, Omer M.; Cervellione, Kelly L.; Singh, Bhupinder B.; Bagheri, Farshad

    2016-01-01

    Pseudogout is a crystal-induced arthropathy characterized by the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in synovial fluid, menisci, or articular cartilage. Although not very common, this entity can be seen in patients with chronic kidney disease (CKD). Septic arthritis due to Mycobacterium avium-intracellulare (MAI) is a rare entity that can affect immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS) or those who are on immunosuppressive drugs. Here, we describe a 51-year-old female who presented with fever, right knee pain, swelling, warmth, and decreased range of motion for several days. The initial assessment was consistent with pseudogout, with negative bacterial and fungal cultures. However, due to high white blood cell (WBC) count in the synovial fluid analysis, she was empirically started on intravenous (IV) vancomycin and piperacillin-tazobactam and discharged on IV vancomycin and cefepime, while acid-fast bacilli (AFB) culture was still in process. Seventeen days later, AFB culture grew Mycobacterium avium-intracellulare (MAI), and she was readmitted for relevant management. This case illustrates that septic arthritis due to MAI should be considered in the differential diagnosis of septic arthritis in immunocompromised patients. PMID:27803833

  10. Oxidation in rheumatoid arthritis

    PubMed Central

    Hitchon, Carol A; El-Gabalawy, Hani S

    2004-01-01

    Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) produced in the course of cellular oxidative phosphorylation, and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. They also serve as important intracellular signaling molecules that amplify the synovial inflammatory–proliferative response. Repetitive cycles of hypoxia and reoxygenation associated with changes in synovial perfusion are postulated to activate hypoxia-inducible factor-1α and nuclear factor-κB, two key transcription factors that are regulated by changes in cellular oxygenation and cytokine stimulation, and that in turn orchestrate the expression of a spectrum of genes critical to the persistence of synovitis. An understanding of the complex interactions involved in these pathways might allow the development of novel therapeutic strategies for rheumatoid arthritis. PMID:15535839

  11. 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

  12. 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.

  13. GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis

    PubMed Central

    Zhang, Juan; Kneuer, Rainer

    2016-01-01

    When SUCNR1/GPR91-expressing macrophages are activated by inflammatory signals, they change their metabolism and accumulate succinate. In this study, we show that during this activation, macrophages release succinate into the extracellular milieu. They simultaneously up-regulate GPR91, which functions as an autocrine and paracrine sensor for extracellular succinate to enhance IL-1β production. GPR91-deficient mice lack this metabolic sensor and show reduced macrophage activation and production of IL-1β during antigen-induced arthritis. Succinate is abundant in synovial fluids from rheumatoid arthritis (RA) patients, and these fluids elicit IL-1β release from macrophages in a GPR91-dependent manner. Together, we reveal a GPR91/succinate-dependent feed-forward loop of macrophage activation and propose GPR91 antagonists as novel therapeutic principles to treat RA. PMID:27481132

  14. 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

  15. Dropped head syndrome in a patient with Aeromonas hydrophila-induced septic arthritis of the shoulder.

    PubMed

    Wang, Sheng-Huei; Juan, Chun-Jung; Lin, Te-Yu

    2014-12-01

    Septic arthritis of the shoulder is very rarely caused by Aeromonas hydrophila. We present the case of a 45-year-old woman who presented with symptoms of painful shoulder for 2 weeks and dropped head for 1 week prior to admission. A. hydrophila was isolated from a culture of purulent synovial fluid. Magnetic resonance imaging revealed profuse abscess collection between the right infraspinatus muscle and trapezius muscle and swelling of the right and left paraspinatus muscles, which suggested myositis-related dropped head syndrome. After surgery with arthrotomy, function of the shoulder and neck extensors was significantly improved.

  16. 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

  17. Mast cells contribute to autoimmune inflammatory arthritis via their tryptase•heparin complexes1

    PubMed Central

    Shin, Kichul; Nigrovic, Peter A.; Crish, James; Boilard, Eric; McNeil, H. Patrick; Larabee, Katherine S.; Adachi, Roberto; Gurish, Michael F.; Gobezie, Reuben; Stevens, Richard L.; Lee, David M.

    2008-01-01

    Although mast cells (MCs) often are abundant in the synovial tissues of patients with rheumatoid arthritis (RA), MC’s contribution to joint inflammation and cartilage loss remains poorly understood. MC-restricted tryptase•heparin complexes have pro-inflammatory activity, and significant amounts of hTryptase-β are present in RA synovial fluid. Mouse MC protease-6 (mMCP-6) is the ortholog of hTryptase-β, and this serine protease is abundant in the synovium of arthritic mice. We now report that C57BL/6 (B6) mice lacking their tryptase•heparin complexes have attenuated arthritic responses, with mMCP-6 as the dominant tryptase responsible for augmenting neutrophil infiltration in the K/B×N mouse serum-transfer arthritis model. While inflammation in this experimental arthritis model was not dependent on protease activated receptor-2, it was dependent on the chemokine receptor CXCR2. In support of the latter data, exposure of synovial fibroblasts to hTryptase-β•heparin or mMCP-6•heparin complexes resulted in expression of the neutrophil chemotactic factors CXCL1/KC, CXCL5/LIX, and CXCL8/IL-8. Our proteomics, histochemistry, and immunohistochemistry data also revealed substantial loss of cartilage-derived aggrecan proteoglycans in the arthritic joints of wild-type B6 mice but not mMCP-6-null B6 mice. These observations demonstrate the functional contribution of MC-restricted tryptase•heparin complexes in the K/B×N mouse arthritis model and connect our mouse findings with RA pathophysiology. PMID:19109198

  18. Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis.

    PubMed

    Chao, Cheng-Chi; Chen, Shi-Juan; Adamopoulos, Iannis E; Davis, Nicole; Hong, Kyu; Vu, Anna; Kwan, Sylvia; Fayadat-Dilman, Laurence; Asio, Agelio; Bowman, Edward P

    2011-05-01

    Interleukin-17A (IL-17A) is a pro-inflammatory cytokine secreted by a subset of memory T cells and other innate immune cells. It is associated with rheumatoid arthritis (RA) due to IL-17A expression in RA synovial fluid. The severe bone erosive rat adjuvant-induced arthritis (rAIA) and mouse collagen-induced arthritis (mCIA) models were used to address the therapeutic efficacy of anti-IL-17A treatment with a focused investigation on bone protection. In the rAIA model, treatment with anti-IL-17A completely alleviated arthritis, lowered the level of receptor activator of NFκB ligand (RANKL), and inhibited structural damage to the bones. In the mCIA model, IL-17A neutralization coincident with arthritis development or in mice with established arthritis diminished joint swelling by inhibiting disease initiation and progression. Intriguingly, even the few joints that became outwardly severely inflamed in the presence of an anti-IL-17A antagonist had diminished joint histopathology scores compared to severely inflamed, control-treated mice. The bone-preserving property correlated with decreased RANKL message in severely inflamed paws of arthritic mice. These data identify IL-17A as a key factor in inflammation-mediated bone destruction and support anti-IL-17A therapy for the treatment of inflammatory bone diseases such as RA.

  19. Platelets: active players in the pathogenesis of arthritis and SLE.

    PubMed

    Boilard, Eric; Blanco, Patrick; Nigrovic, Peter A

    2012-09-01

    Nearly one trillion platelets circulate in the blood to monitor and preserve the integrity of the vasculature. However, haemostasis is not their only function. Platelets are also potent immune cells capable of a range of effector responses. Studies have shown that platelets can have unexpected roles in rheumatic diseases. In patients with rheumatoid arthritis (RA), IL-1-containing platelet-derived vesicles called microparticles are abundant in arthritic joint fluid. These microparticles can elicit production of inflammatory mediators from resident synovial fibroblasts, which have an integral role in the development of arthritis. Platelets also serve as a source of prostaglandins that contribute to synovial inflammation. Furthermore, serotonin released by platelets helps drive the persistent vascular permeability that characterizes the microvasculature of the inflamed synovium, an unexpected function for a cell that more typically serves as a guardian of vascular integrity. Beyond RA, platelet activation has been observed in systemic lupus erythematosus, mediated at least in part through the interaction of circulating immune complexes with platelet Fc receptors and by promotion of interferon release from plasmacytoid dendritic cells. These findings point to a distinct role for platelets in autoimmunity and support the possibility that platelets are an attractive target in rheumatic disease.

  20. Molecular identification of Bartonella species in dogs with leishmaniosis (leishmania infantum) with or without cytological evidence of arthritis.

    PubMed

    Mylonakis, Mathios E; Soubasis, Nectarios; Balakrishnan, Nandhakumar; Theodorou, Konstantina; Kasabalis, Dimitrios; Saridomichelakis, Manolis; Koutinas, Christos K; Koutinas, Alexander F; Breitschwerdt, Edward B

    2014-11-07

    Recent evidence suggest that Bartonella species may cause polyarthritis and lameness in dogs. Canine leishmaniosis (CanL) due to Leishmania infantum is a multi-systemic disease often occurring in association with arthritis. We hypothesized that concurrent Bartonella infection may be a contributing factor for the development of arthritis in dogs with CanL. Hence the primary objective of this study was to investigate the molecular prevalence of Bartonella spp. in dogs with naturally occurring CanL, with or without cytologically documented arthritis. Thirty-eight dogs with CanL (31 with neutrophilic arthritis and 7 without arthritis) were retrospectively studied. Seventy-four archived clinical specimens from these 38 dogs, including 33 blood samples, 19 bone marrow (BM) samples and synovial fluid (SF) aspirates from 22 dogs were tested for Bartonella spp. DNA using the Bartonella alpha proteobacteria growth medium (BAPGM) diagnostic platform. Overall, eight (21.1%) dogs were infected with one or two Bartonella species; however, Bartonella spp. infection was not associated with arthritis in dogs with CanL. Further prospective studies are warranted to determine if there is a correlation between Bartonella spp. infection and the development of arthritis in dogs with CanL.

  1. 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

  2. Treatment with anti-NAP monoclonal antibody reduces disease severity in murine model of novel angiogenic protein-induced or ovalbumin-induced arthritis.

    PubMed

    Nataraj, N B; Krishnamurthy, J; Salimath, B P

    2013-02-01

    Rheumatoid arthritis (RA) is a polyarticular inflammatory, angiogenic disease. Synovial angiogenesis contributes to inflammation in RA. In this study we have developed an arthritic model in rats using a novel angiogenic protein (NAP), isolated from human synovial fluid of RA patients. We produced anti-NAP monoclonal antibodies (mAbs) and investigated the therapeutic efficacy of the same in adjuvant-induced or NAP-induced arthritis as a model of human RA. The treatment of arthritic rats with anti-NAP mAbs resulted in effective amelioration of paw oedema, radiological arthritic characteristics, serum levels of vascular endothelial growth factor (VEGF) and NAP, compared to that of untreated arthritic animals. Further, profiling of angiogenic markers such as synovial microvessel density, angiogenesis, CD31, VEGF and fms-like tyrosine kinase (Flt1) by immunohistochemistry both in arthritic and anti-NAP mAb-treated animals revealed the efficacy of mAb as an anti-angiogenic functional antibody. Therefore, NAP may be an attractive target to design anti-angiogenic and anti-arthritic therapies to control the pathogenesis of arthritis.

  3. Differential expression of the urokinase receptor (CD87) in arthritic and normal synovial tissues.

    PubMed Central

    Szekanecz, Z; Haines, G K; Koch, A E

    1997-01-01

    AIM: To determine whether the urokinase plasminogen activator receptor (u-PAR; CD87) exhibits a possible pathogenic role in rheumatoid and osteoarthritis. METHODS: A semiquantitative, indirect immunoperoxidase histochemical analysis was performed on frozen synovial tissue sections. The recently characterised monoclonal antibody 10G7 recognising transfectants bearing u-PAR was used. Synovial tissue was obtained from 10 patients with rheumatoid arthritis, 10 patients with osteoarthritis, and four normal subjects. RESULTS: u-PAR was expressed on 70-90% of synovial tissue lining cells and subsynovial, interstitial macrophages from the arthritis patients, but only on a few myeloid cells from the normal subjects. It was also present on more endothelial cells from the rheumatoid and osteoarthritis patients, than from normal synovial tissue. CONCLUSIONS: Plasminogen activators are important in joint destruction underlying arthritis. The up-regulated expression of u-PAR in diseased versus normal synovial tissue suggests a role for this antigen in the inflammatory and angiogenic mechanisms underlying rheumatoid and osteoarthritis. Images PMID:9215148

  4. Neisseria meningitidis Serogroup C Causing Primary Arthritis in a Child

    PubMed Central

    Straticiuc, Sergiu; Ignat, Ancuta; Hanganu, Elena; Lupu, Vasile Valeriu; Ciubara, Alexandru Bogdan; Cretu, Roxana

    2016-01-01

    Abstract Introduction: Neisseria meningitidis (N. meningitidis) is associated with severe invasive infections such as meningitis and fulminant septicemia. Septic arthritis due to N. meningitidis is rare and bone infections have been reported exceptionally. We report the case of a 1-year old girl who presented with a painful, swollen right knee, accompanied by fever and agitation. Arthrocentesis of the right knee, while patient was under anesthesia, yielded grossly purulent fluid, so we made arthrotomy and drainage. The culture from synovial fluid revealed N. meningitidis, sensitive to Ceftriaxone. The patient received intravenous antibiotherapy with Ceftriaxone. The status of the patient improved after surgical drainage and intravenous antibiotic therapy. She recovered completely after 1 month. Conclusion: This observation illustrates an unusual presentation of invasive meningococcal infection and the early identification of the bacteria, combined with the correct treatment, prevent the complications and even death. PMID:26844522

  5. Cells of the synovium in rheumatoid arthritis. Chondrocytes.

    PubMed

    Otero, Miguel; Goldring, Mary B

    2007-01-01

    Rheumatoid arthritis (RA) is one of the inflammatory joint diseases in a heterogeneous group of disorders that share features of destruction of the extracellular matrices of articular cartilage and bone. The underlying disturbance in immune regulation that is responsible for the localized joint pathology results in the release of inflammatory mediators in the synovial fluid and synovium that directly and indirectly influence cartilage homeostasis. Analysis of the breakdown products of the matrix components of joint cartilage in body fluids and quantitative imaging techniques have been used to assess the effects of the inflammatory joint disease on the local remodeling of joint structures. The role of the chondrocyte itself in cartilage destruction in the human rheumatoid joint has been difficult to address but has been inferred from studies in vitro and in animal models. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the disruption of the integrity of the cartilage matrix in RA.

  6. 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

  7. Synovial Cyst Mimicking an Intraspinal Sacral Mass

    PubMed Central

    2014-01-01

    A 68-year-old female had a three-week history of severe low back pain radiating down the posterior left buttocks and left leg exacerbated by standing and walking. Lumbar spine MRI revealed cystic mass with similar intensity to cerebrospinal fluid located on dorsolateral left side of the sacral spinal canal inferior to the S1 pedicle. There was compression of left exiting S1 and traversing S2 nerve roots. Neurosurgery consult was requested to evaluate the cystic mass in the sacral spinal canal. After clinical evaluation, an unusually located synovial cyst was thought possible. Cyst contents were heterogeneous, suggestive of small hemorrhage and acute clinical history seemed reasonable. Left S1 and partial left S2 hemilaminectomy was performed and an epidural, partially hemorrhagic cyst was removed. There was no obvious connection to the ipsilateral L5-S1 facet joint. Pathology revealed synovial cyst, and the patient's leg pain was improved postoperatively. This synovial cyst was unusual as it had no connection with the facet joint intraoperatively and its location in the sacral canal was uncommon. PMID:24716025

  8. Gout: epitome of painful arthritis.

    PubMed

    VanItallie, Theodore B

    2010-10-01

    monosodium urate (MSU), calcium pyrophosphate dehydrate, or basic calcium phosphate crystals. The innate immune system rapidly detects invading pathogenic microbes and nonmicrobial "danger signals" such as MSU crystals. When these crystals are deposited in synovial tissues, NLR proteins (NOD-like receptors) form multiprotein complexes known as inflammasomes that trigger secretion of inflammation-producing cytokines like interleukin-1β and interleukin-18. Usually, gout can be diagnosed by medical history, physical examination, and presence of hyperuricemia (urate >416 μmol/L). However, a urate concentration less than 416 does not by itself rule out gout. Confirmation of the diagnosis by identification of typical MSU crystals in aspirated synovial fluid is definitive. Analysis of joint fluid is mandatory to rule out septic arthritis, which can rapidly become lethal. Because of its special ability to identify and quantitate urate deposits in peripheral tissues, dual-energy computed tomography should prove valuable in the differential diagnosis of gout. Gout mimics a variety of illnesses; for example, spinal gout may masquerade as metastatic cancer, epidural abscess, and nerve compression syndrome.

  9. Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 2: clinical features, diagnosis and differential diagnostics.

    PubMed

    Schlee, S; Bollheimer, L C; Bertsch, T; Sieber, C C; Härle, P

    2017-02-23

    Gout develops in four stages beginning with an asymptomatic increase in blood levels of uric acid. An acute gout attack is an expression of an underlying inflammatory process, which in the course of time is self-limiting. Without therapy monosodium urate crystals remain in the synovial fluid and synovial membrane and trigger more acute attacks. In the course of the disease monosodium urate crystals form deposits (tophi) leading in severe forms to irreversible joint deformities with loss of functionality. In 20% of cases gout leads to involvement of the kidneys. Overproduction of uric acid can cause nephrolithiasis. These stones can be composed of uric acid or calcium phosphate. Another form of kidney disease caused by gout is uric acid nephropathy. This is a form of abacterial chronic inflammatory response with deposition of sodium urate crystals in the medullary interstitium. Acute obstructive nephropathy is relatively rare and characterized by renal failure due to uric acid precipitation in the tubules because of rapid cell lysis that occurs, for example, with chemotherapy. There is a causal interdependence between the occurrence of hyperuricemia and hypertension. Uric acid activates the renin-angiotensin-aldosterone (RAA) system and inhibits nitric oxide (NO) with the possible consequence of a rise in systemic vascular resistance or arteriolar vasculopathy; however, uric acid is also an apparently independent risk factor for atherosclerosis. In contrast to young patients, the diagnosis of an acute gout attack in the elderly can be a challenge for the physician. Polyarticular manifestations and obscure symptoms can make it difficult to differentiate it from rheumatoid arthritis and calcium pyrophosphate deposition disease (CPPD). Aspiration of synovial fluid with visualization of urate crystals using compensated polarized light microscopy is the gold standard for diagnosis of acute gout. Moreover, analysis of synovial fluid enables a distinction from septic

  10. The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis.

    PubMed

    Paulissen, Sandra M J; van Hamburg, Jan Piet; Dankers, Wendy; Lubberts, Erik

    2015-07-01

    The IL-17A producing T-helper-17 (Th17) cell population plays a major role in rheumatoid arthritis (RA) pathogenesis and has gained wide interest as treatment target. IL-17A expressing Th cells are characterized by the expression of the chemokine receptor CCR6 and the transcription factor RORC. In RA, CCR6+ Th cells were identified in peripheral blood, synovial fluid and inflamed synovial tissue. CCR6+ Th cells might drive the progression of an early inflammation towards a persistent arthritis. The CCR6+ Th cell population is heterogeneous and several subpopulations can be distinguished, including Th17, Th22, Th17.1 (also called non-classic Th1 cells), and unclassified or intermediate populations. Interestingly, some of these populations produce low levels of IL-17A but are still very pathogenic. Furthermore, the CCR6+ Th cells phenotype is unstable and plasticity exists between CCR6+ Th cells and T-regulatory (Treg) cells and within the CCR6+ Th cell subpopulations. In this review, characteristics of the different CCR6+ Th cell populations, their plasticity, and their potential impact on rheumatoid arthritis are discussed. Moreover, current approaches to target CCR6+ Th cells and future directions of research to find specific CCR6+ Th cell targets in the treatment of patients with RA and other CCR6+ Th cell mediated autoimmune diseases are highlighted.

  11. Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

    PubMed Central

    Norling, Lucy V.; Headland, Sarah E.; Arnardottir, Hildur H.; Haworth, Oliver; Jones, Hefin R.; Serhan, Charles N.

    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. Editorial Commentary: Role of Synovial Biomarkers in Patient Outcomes After Knee Arthroscopy.

    PubMed

    Brand, Jefferson C

    2016-03-01

    Humans are notably poor at predicting event outcomes. In "Correlation of Synovial Fluid Biomarkers With Cartilage Pathology and Associated Outcomes in Knee Arthroscopy," Cuellar, Cuellar, Kirsch, and Strauss show that some synovial fluid biomarkers (20 were sampled for the investigation) may predict operative findings at the time of arthroscopy and patient-reported outcome measures at follow-up. Further research will clarify the role of synovial biomarkers in knee pathology and, hopefully, narrow the choices to one or two pertinent markers that can be used to improve our ability to predict outcomes from arthroscopic knee surgery.

  13. 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

  14. Importance of timing of post-contrast MRI in rheumatoid arthritis: what happens during the first 60 minutes after IV gadolinium-DTPA?

    PubMed Central

    Ostergaard, M; Klarlund, M

    2001-01-01

    BACKGROUND—Volumes of inflamed synovial membrane determined by magnetic resonance imaging (MRI) are closely related to histopathological synovitis and may predict erosive progression in rheumatoid arthritis (RA). However, after IV injection, leakage of MRI contrast from the synovium gradually compromises the differentiation of synovium from joint fluid.
OBJECTIVE—To determine the time period after IV MRI contrast (gadolinium-DTPA (Gd)) injection in which synovial membrane volume determination is reliable.
METHODS—MRI of five RA knees with clinical synovitis was carried out, with axial, T1 weighted, spin echo images before IV Gd injection and every 1.75 minutes for 60 minutes post-Gd. By a semiautomated "signal enhancement threshold" method, including voxels with >35% or >45% relative post-Gd enhancement, synovial membrane volumes were estimated at each time point. At 4.25 minutes post-Gd, volumes were also determined by a more accurate but time consuming "manual method".
RESULTS—The initially observed synovium-effusion borderline remained clearly visible, and on the same location, within at least the initial 11 minutes post-Gd (that is, within the normal time frame of post-Gd imaging in RA) but started blurring and moving centripetally thereafter. Compared with volumes at all other time points, synovial membrane volumes at 0.75 and 2.50 minutes post-Gd were significantly lower (Wilcoxon-Pratt), suggesting that some synovial membrane areas had not yet exceeded the enhancement threshold. Thereafter, the measured volumes remained practically unchanged.
CONCLUSION—This study suggests that MR image acquisition in arthritic knee joints should be performed within the initial approximately 10 minutes after gadolinium contrast injection to achieve the most accurate distinction between synovium and joint fluid but that small time variations are not of major importance to the measured synovial membrane volumes.

 PMID:11602477

  15. Is it easy to clinically distinguish inflammatory arthritis of bacterial origin from monoarthritis attacks of gout disease?

    PubMed

    Atik, O Şahap; Ergişi, Yılmaz; Ayanoğlu, Tacettin; Tokgöz, Mehmet Ali; Sezgin, Erdem Aras; Göçün, Pınar Uyar

    2016-12-01

    Acute monoarthritis is a common situation in orthopedic emergency where the patient presents with typical inflamed joint. It is hard to clinically distinguish inflammatory arthritis of bacterial origin from monoarthritis attacks of gout disease. If these two situations, which are the most common causes of acute monoarthritis, are misdiagnosed, outcomes might be catastrophic and costly. Synovial fluid analysis is the most reliable method for confirming the diagnosis although it might not always lead to definitive diagnosis. If there is clinical suspicion for crystal arthropathy, repeated examinations may provide benefits for confirming the diagnosis.

  16. Cytokines in rheumatoid arthritis.

    PubMed

    Vervoordeldonk, Margriet J B M; Tak, Paul P

    2002-06-01

    Rheumatoid arthritis (RA) is a chronic disease characterized by synovial inflammation that leads to the destruction of cartilage and bone. In the last decade, there was a lot of successful research in the field of cytokine expression and regulation. It has become clear that pro- and anti-inflammatory cytokines, derived predominantely from cells of macrophage lineage, play a major role in the initiation and perpetuation of the chronic inflammatory process in the RA synovial membrane. Monokines are abundant in rheumatoid synovial tissue, whereas low amounts of lymphokines are found. The involvement of pro-inflammatory cytokines, particularly interleukin (IL)-1 and tumor necrosis factor-alpha, in the pathogenesis of RA is well accepted. Recent data provide evidence that the pro-inflammatory cytokine IL-18 plays a crucial role in the development and sustenance of inflammatory joint diseases. There also appears to be a compensatory anti-inflammatory response in RA synovial membrane. It has become clear in the last few years that T cell-derived cytokines expressed preferentially by Th1 cells contribute to joint destruction and inflammation in RA. However, products from Th2 cells may be protective.

  17. 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.

  18. 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. ...

  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

    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.

  20. Bacteria and Toll-like receptor and cytokine mRNA expression profiles associated with canine arthritis.

    PubMed

    Riggio, Marcello P; Lappin, David F; Bennett, David

    2014-08-15

    The major forms of inflammatory canine arthritis are immune-mediated arthritis (IMA) and septic arthritis (SA), although some cases of cruciate disease (CD) are associated with significant levels of synovitis. In this study, the bacteria associated with canine arthritis were identified and mRNA expression levels of Toll-like receptors (TLRs) and pro-inflammatory cytokines determined. Of the 40 synovial fluid samples analysed, bacteria were isolated from 12 samples by culture (2 CD, 10 SA) and detected in 4 samples (3 CD, 1 SA) using culture-independent methods. Statistically significant increases in TLR2, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-12 mRNA expression were seen in all disease groups compared to normal controls. All disease groups had decreased mRNA expression of other TLRs compared to normal controls, but this did not reach statistical significance. Synovial fluid cell counts revealed that the highest number and proportion of mononuclear cells and neutrophils were found in the IMA and SA samples, respectively. Age had an effect on the TLR and cytokine mRNA expression profiles: TNF-α (p=0.043) and IL-12 (p=0.025) mRNA expression was increased and TLR4 mRNA expression was reduced (p=0.033) in dogs up to 4 years of age compared to older animals. In the 10 SA samples from which bacteria were isolated, statistically significant increases in TLR2, TLR7, TNF-α and IL-6 mRNA expression were observed. It is concluded that canine arthritis is associated with increased mRNA levels of pro-inflammatory cytokines, which could in some cases be mediated by bacteria through activation of TLR2.

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

    PubMed

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

    2010-04-01

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

  2. 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.

  3. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies.

    PubMed

    Song, Y W; Kang, E H

    2010-03-01

    Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease, characterized by chronic, erosive polyarthritis and by the presence of various autoantibodies in serum and synovial fluid. Since rheumatoid factor (RF) was first described, a number of other autoantibodies have been discovered in RA patients. The autoantigens recognized by these autoantibodies include cartilage components, chaperones, enzymes, nuclear proteins and citrullinated proteins. However, the clinical significances and pathogenic roles of these antibodies are largely unknown except for RF and anticitrullinated protein antibodies (ACPAs), whose clinical usefulness has been acknowledged due to their acceptable sensitivities and specificities, and prognostic values. This review presents and discusses the current state of the art regarding RF and ACPA in RA.

  4. Rheumatoid Arthritis

    MedlinePlus

    ... Education Visitor Information RePORT NIH Fact Sheets Home > Rheumatoid Arthritis Small Text Medium Text Large Text Rheumatoid Arthritis Rheumatoid arthritis is an inflammatory disease affecting about ...

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

    PubMed

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

    2012-10-01

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

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

    PubMed

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

    2012-10-01

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

  7. Fungal arthritis of the knee caused by Mycoleptodiscus indicus.

    PubMed

    Dewar, Catharine L; Sigler, Lynne

    2010-09-01

    Mycoleptodiscus indicus is a recognized plant pathogen which has very rarely been reported as a cause of human infection. It is a tropical or subtropical fungus which is difficult to culture and identify from clinical specimens. This is the first report of septic arthritis with this fungus in a healthy Canadian male. The fungal infection was contracted on a vacation in Costa Rica, probably through direct inoculation through injured skin. The fungus was isolated from synovial fluid and identification was confirmed by DNA sequencing. There has only been one previous case of septic arthritis of the knee and one skin infection reported with this fungus; both cases involved immunocompromised hosts. Both septic arthritis patients required joint surgery and lavage to eradicate the fungus, however, only the immunocompromised patient required antifungal medications. In the future, it is very likely that the number of patients identified with M. indicus infection will rise due to increasing awareness of this pathogen as well as increasing exposure. Many immunocompromised patients on anti-retroviral or biologic therapy are healthy enough to travel, thereby exposing themselves to exotic and infected plants which increase the risk of unusual fungal infections.

  8. Recent advances in neutralizing the IL-6 pathway in arthritis

    PubMed Central

    Malemud, Charles J

    2009-01-01

    Recent advances in understanding the mechanism(s) of how IL-6 trans-signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. Serum and/or synovial fluid (SF) IL-6 is markedly elevated in adult and juvenile rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and osteoarthritis (OA). IL-6, in concert with IL-17, determines the fate of CD4+ lymphocytes and therefore TH17 cell differentiation. IL-6 also plays a critical role in modulating B-lymphocyte activity. The recognition that IL-6 trans-signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R). Significant clinical benefit was demonstrated as well as reduced serum IL-6 levels with suppression of X-ray progression of disease in several clinical trials in which juvenile or adult RA patients were treated with tocilizumab monotherapy or tocilizumab plus methotrexate. However, levels of serum and/or SF IL-6 cytokine protein superfamily members, adiponectin, oncostatin M, pre-B-cell colony enhancing factor/visfatin and leukemia inhibitory factor are also elevated in RA. Additional studies will be required to determine if anti-IL-6 trans-signaling inhibition strategies with tocilizumab or recombinant soluble IL-6R reduce the level of these cytokines. PMID:27789987

  9. Some historical remarks on microcrystalline arthritis (gout and chondrocalcinosis).

    PubMed

    Marson, P; Pasero, G

    2012-01-19

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

  10. Septic arthritis and osteomyelitis in a 10-year-old boy, caused by Fusobacterium nucleatum, diagnosed with PCR/16S ribosomal bacterial DNA amplification

    PubMed Central

    Kroon, Elke; Arents, Niek A; Halbertsma, Feico Jan

    2012-01-01

    A 10-year-old boy presented with an atypical non-febrile septic arthritis/osteomyelitis. He was unresponsive to routine antibiotic treatment with flucloxacillin/gentamicin as the pain and fluid collection increased. Synovial fluid cultures are negative and gram stain remained negative. Only after PCR/16S ribosomal bacterial DNA amplification a Fusobacterium nucleatum could be detected, and antibiotic therapy switched to clindamycin with rapid response. Septic osteomyelitis and arthritis are relatively rare but important infections in children needing prompt treatment, and should be considered when a child complaints about joint or bone pain without prior recent trauma. Skin bacteria are the most prevalent causative organisms, whereas Fusobacteria or other anaerobic, Gram-negative microorganisms are very seldom encountered. If cultures remain negative and the patients responds insufficiently to empiric treatment, PCR/16S ribosomal bacterial DNA amplification can be useful to detect the causative microorganisms. PMID:22605875

  11. Fungal arthritis and osteomyelitis.

    PubMed

    Kohli, Rakhi; Hadley, Susan

    2005-12-01

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

  12. Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated monocytes in rheumatoid arthritis.

    PubMed

    Cassatella, Marco A; Pereira-da-Silva, Gabriela; da Silva, Gabriela Pereira; Tinazzi, Ilaria; Facchetti, Fabio; Scapini, Patrizia; Calzetti, Federica; Tamassia, Nicola; Wei, Ping; Nardelli, Bernardetta; Roschke, Viktor; Vecchi, Annunciata; Mantovani, Alberto; Bambara, Lisa M; Edwards, Steven W; Carletto, Antonio

    2007-06-01

    TNF-like cytokine (TL1A) is a newly identified member of the TNF superfamily of ligands that is important for T cell costimulation and Th1 polarization. However, despite increasing information about its functions, very little is known about expression of TL1A in normal or pathological states. In this study, we report that mononuclear phagocytes appear to be a major source of TL1A in rheumatoid arthritis (RA), as revealed by their strong TL1A expression in either synovial fluids or synovial tissue of rheumatoid factor (RF)-seropositive RA patients, but not RF-/RA patients. Accordingly, in vitro experiments revealed that human monocytes express and release significant amounts of soluble TL1A when stimulated with insoluble immune complexes (IC), polyethylene glycol precipitates from the serum of RF+/RA patients, or with insoluble ICs purified from RA synovial fluids. Monocyte-derived soluble TL1A was biologically active as determined by its capacity to induce apoptosis of the human erythroleukemic cell line TF-1, as well as to cooperate with IL-12 and IL-18 in inducing the production of IFN-gamma by CD4(+) T cells. Because RA is a chronic inflammatory disease with autoimmune etiology, in which ICs, autoantibodies (including RF), and various cytokines contribute to its pathology, our data suggest that TL1A could be involved in its pathogenesis and contribute to the severity of RA disease that is typical of RF+/RA patients.

  13. Detection of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis patients undergoing total knee arthroplasty.

    PubMed

    Guo, Chong-Jun; Lv, Jin-Han; Niu, Dong-Sheng; Ma, Tao; Sun, Shou-Xuan; Li, Li-Xin; Zhao, Xin; Wu, Long; Jin, Qun-Hua

    2015-01-01

    Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disorder and anti-cyclic citrullinated peptide antibody (anti-CCP Ab) is regarded as a serological marker for diagnosing early and late RA. In the present study, we aimed to determine the levels of anti-CCP Ab in serum, synovial tissue (ST) and synovial fluid (SF) in RA patients undergoing total knee arthroplasty (TKA). 23 patients were included. Rheumatoid factor (RF) and anti-CCP Ab in serum were detected prior to surgery and then at 1, 3, 6 and 12 months after TKA. Synovial samples were obtained by knee arthroscopy and used for anti-CCP detection. One month after TKA, anti-CCP levels were significantly reduced (P < 0.01) in RA patients. However, their levels were not significantly different between pre-surgery and 1 year post-surgery (P > 0.05). Furthermore, anti-CCP levels in ST were much higher than in serum. These findings suggest that RA patients should continue antirheumatic therapy after TKA. ST is the preferred place for the synthesis of anti-CCP Ab.

  14. 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.

  15. TNF inhibition as therapy for rheumatoid arthritis.

    PubMed

    Wollheim, Frank A

    2002-07-01

    The introduction of TNF- alpha -inhibiting biologicals has been a major therapeutic breakthrough in rheumatoid arthritis therapy. Against a background of conventional disease-modifying antirheumatic drug experience, this review focuses on present experiences and possible future developments. TNF inhibition results in profound improvement in the majority of rheumatoid arthritis patients, but non-response and adverse effects need attention. Adalimumab is being filed for approval. Other monoclonal antibodies or receptor constructs are in late development. Small molecule inhibitors of TNF production or signalling are a hot topic. One emerging target is nuclear factor kappa B and selective inhibition has proved effective in animal models of arthritis. Synovial proliferation in rheumatoid arthritis is characterised by diminished apoptosis of fibroblasts, whereas bone marrow precursor cells undergo accelerated apoptosis in active rheumatoid arthritis. Both abnormalities are seemingly ameliorated by TNF inhibition. Anti-apoptotic strategies will soon go into development for control of unresponsive rheumatoid arthritis.

  16. Galectin-3 is a sensor-regulator of toll-like receptor pathways in synovial fibroblasts.

    PubMed

    Arad, Uri; Madar-Balakirski, Noa; Angel-Korman, Avital; Amir, Sharon; Tzadok, Sharon; Segal, Ortal; Menachem, Aharon; Gold, Aviram; Elkayam, Ori; Caspi, Dan

    2015-05-01

    Galectin-3 is a β-galactoside-binding lectin that plays an important role in the modulation of immune responses. It has been shown to aggravate joint inflammation and destruction in experimental arthritis. We investigated the role of galectin-3 in TLR-induced cell activation in human synovial fibroblasts (SF) in order to better understand the mechanism(s) of the proinflammatory function of galectin-3 in arthritis. Galectin-3 expression in SF obtained from rheumatoid arthritis and osteoarthritis patients was inhibited by siRNA mediated gene-knockdown. Galectin-3 was also inhibited with modified citrus pectin (MCP), a polysaccharide galectin-3 ligand. Galectin-3 knockdown inhibited TLR-2, -3 and -4-induced IL-6 secretion, but not TLR-2, -3 and -4-mediated matrix metalloproteinase-3 or CC chemokine ligand-5 secretion. When the SF were stimulated with phorbol 12-myristate 13-acetate, a protein kinase C activator that bypasses the membranal receptors, galectin-3 knockdown no longer influenced IL-6 secretion. MCP reduced IL-6 levels in a dose-dependent manner. Our results indicate that galectin-3 is a positive sensor-regulator of TLR-induced IL-6 secretion in human synovial fibroblasts, thus adding new insights into the mechanisms by which galectin-3 augments synovial inflammation. These findings corroborate the potential role of glycan inhibitors of galectin-3 as a therapeutic approach for the treatment of inflammatory arthritis.

  17. Transforming growth factor-beta 1 in rheumatoid synovial membrane and cartilage/pannus junction.

    PubMed

    Chu, C Q; Field, M; Abney, E; Zheng, R Q; Allard, S; Feldmann, M; Maini, R N

    1991-12-01

    Transforming growth factor (TGF)-beta has been shown to promote tissue repair and have immunosuppressive actions, and has been proposed to have a role in rheumatoid arthritis (RA). Using immunohistochemical techniques with rabbit F(ab')2 antibodies raised against recombinant human TGF-beta 1, we have detected TGF-beta 1 in the synovial tissue and cartilage/pannus junction (CPJ) from 18/18 patients with RA. TGF-beta 1 was found predominantly in the thickened synovial lining layer in RA, but also detected in a perivascular pattern in the synovial interstitium as well as in occasional cells in the lymphoid aggregates. At the CPJ it was found both in cells at the distinct junction as well as in the transitional region of the diffuse fibroblastic zone. The cells staining for TGF-beta 1 were identified by double immunofluorescence staining as being from the monocyte/macrophage series as well as the type B synovial lining cells. TGF-beta 1 was also detected in the synovial membrane sections from 4/4 patients with systemic lupus erythematosus/mixed connective tissue disease and 5/8 patients with osteoarthritis, in a similar distribution to that seen in RA, and in the lining layer of 1/7 normal synovial membranes. These results add to histological evidence confirming that TGF-beta 1 is present in RA synovial cells and those from other arthritides. The distributions of TGF-beta 1 in RA synovial membrane reflects its known actions, as it can be detected at the CPJ, where it could induce repair, and close to activated cells upon which it may exert an immunosuppressive action.

  18. Postlaminectomy Bilateral Lumbar Intraspinal Synovial Cysts

    PubMed Central

    Cho, Sung Ik; Lee, Jung Hwan

    2016-01-01

    Lumbar intraspinal synovial cysts are included in the difference diagnosis of lumbar radiculopathy. Developing imaging modalities has result in increased reporting about these lesions. However, the case of bilateral new lumbar intraspinal synovial cysts after laminectomy has been rarely reported. We report of a rare case with bilateral lumbar intraspinal synovial cysts after laminectomy, requiring surgical excision. PMID:27799997

  19. Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis.

    PubMed Central

    Koch, A E; Kunkel, S L; Harlow, L A; Johnson, B; Evanoff, H L; Haines, G K; Burdick, M D; Pope, R M; Strieter, R M

    1992-01-01

    Cells within the synovial tissue may recruit mononuclear phagocytes into the synovial fluid and tissues of arthritic patients. We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP-1 levels were significantly higher (P less than 0.05) in synovial fluid from RA patients (mean 25.5 +/- 8.1 ng/ml [SE]) compared to synovial fluid from osteoarthritis (OA) patients (0.92 +/- 0.08), or from patients with other arthritides (2.9 +/- 1.5). MCP-1 levels in RA sera (8.44 +/- 2.33) were significantly greater than MCP-1 in normal sera (0.16 +/- 0.06). The quantities of RA synovial fluid IL-8, which is chemotactic for neutrophils and lymphocytes, and MCP-1 were strongly positively correlated (P less than 0.05). To examine the cellular source of MCP-1, RA synovial tissue macrophages and fibroblasts were isolated. Synovial tissue fibroblasts did not express MCP-1 mRNA, but could be induced to produce MCP-1 by stimulation with either IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), or LPS. In contrast, unlike normal peripheral blood monocytes or alveolar macrophages, RA synovial tissue macrophages constitutively expressed MCP-1 mRNA and antigen. Immunohistochemical analysis of synovial tissue showed that a significantly greater percentage of RA macrophages (50 +/- 8%) as compared to either OA macrophages (5 +/- 2) or normal macrophages (1 +/- 0.3) reacted with anti-MCP-1 antibodies. In addition, the synovial lining layer reacted with MCP-1 in both RA and OA synovial tissues. In contrast, only a minority of synovial fibroblasts (18 +/- 8%) from RA synovium were positive for immunolocalization of MCP-1. These results suggest that synovial production of MCP-1 may play an important role in the recruitment of mononuclear phagocytes during inflammation associated with RA and that synovial

  20. Upregulated expression of CCR3 in rheumatoid arthritis and CCR3-dependent activation of fibroblast-like synoviocytes.

    PubMed

    Liu, Xin; Zhang, Huiyun; Chang, Xin; Shen, Jirong; Zheng, Wenjiao; Xu, Yanan; Wang, Junling; Gao, Wei; He, Shaoheng

    2017-02-01

    It is recognized that CC chemokine receptor 3 (CCR3) is associated with numerous inflammatory conditions and fibroblast-like synoviocyte (FLS) invasiveness correlates with articular damage in rheumatoid arthritis (RA). However, little is known of the expression and action of CCR3 on FLS in RA. In the present study, we investigated the expression of CCR3 on dispersed synovial tissue and peripheral blood cells in RA and influence of eotaxin-1 on FLS functions by using flow cytometry analysis, FLS challenge, and real-time PCR techniques. The results showed that approximately 7.0 % dispersed synovial cells are CCR3+ cells. Among those CCR3+ cells, 38.1, 23.8, and 20.6 % cells are CD90+CD14-CD3- (representing FLS), CD14+, and CD8+ cells, respectively, indicating that FLS is one of the major populations of CCR3+ cells in the synovial tissue of RA. In peripheral blood, CD14+ CCR3+ cells are elevated, but CD8+CCR3+ cells are reduced in RA. It was found that eotaxin-1 induced upregulated expression of CCR3 and matrix metalloproteinase (MMP)-9 messenger RNAs (mRNAs) in FLS. Since an antagonist of CCR3 suppressed the action of eotaxin-1, the event appeared CCR3 dependent. Moreover, we observed that interleukin (IL)-1β induced markedly enhanced eotaxin-1 release from FLS, but TNF-α reduced eotaxin-1 release at 12 and 24 h following incubation. In conclusion, enhanced expression of CCR3 on synovial cells and increased levels of eotaxin-1 in plasma and synovial fluid (SF) of RA indicate that CCR3-mediated mechanisms may play an important role in RA. Blockage of eotaxin-1 provoked CCR3 and MMP-9 expression in FLS by antagonist of CCR3, implicating that anti-CCR3 agents may have therapeutic use for RA.

  1. Chronic gonococcal arthritis with C5 deficiency presenting with brief flare-ups: case study and literature review.

    PubMed

    Davido, B; Dinh, A; Lagrange, A; Mellon, G; de Truchis, P; Perronne, C; Cremieux, A C

    2014-09-01

    Gonococcal arthritis is typically acute and appears within 3 weeks after initial infection. Chronic gonococcal arthritis is now exceptionally rare, since the advent of the antibiotic era. Numerous host factors are involved in gonococcal dissemination, such as complement deficiency, HIV and gonococcus strain characteristics. Gonococcal arthritis shares the same risk factors. In this instance, our patient was a 16-year-old girl suffering from persistent polyarthralgia with joint swelling presenting with brief flare-ups for a period of 1 year. She disclosed a single episode of unprotected sexual intercourse 1 year ago, i.e. just before developing her first rheumatological symptoms. Therefore, we performed a joint aspiration (arthrocentesis), and synovial fluid was inoculated directly into aerobic and anaerobic blood culture bottles, which tested positive for Neisseria gonorrhoeae within 24 h. Clinical presentation was consistent with previous reports of chronic gonococcal arthritis. Further investigation revealed a C5 complement deficiency, which might explain the chronic Neisseria process. A favourable outcome was reached after a ten-day course of IV ceftriaxone, with no apparent sequelae found during follow-up 6 weeks later. This case demonstrates an unusual gonococcal arthritis with brief flare-ups for the course of a year, followed by a subacute form. N. meningitidis infections, similar to N. gonorrhoeae, are typically acute and may sometimes be involved in chronic processes. However, this characteristic appears to be rare in the case of N. gonorrhoeae. Risk factors for this chronic process will be discussed with a review of the literature.

  2. Update on Therapeutic Approaches for Rheumatoid Arthritis.

    PubMed

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

    2016-01-01

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

  3. NETosis as Source of Autoantigens in Rheumatoid Arthritis

    PubMed Central

    Corsiero, Elisa; Pratesi, Federico; Prediletto, Edoardo; Bombardieri, Michele; Migliorini, Paola

    2016-01-01

    In neutrophils (but also in eosinophils and in mast cells), different inflammatory stimuli induce histone deimination, chromatin decondensation, and NET formation. These web-like structures that trap and kill microbes contain DNA, cationic granule proteins, and antimicrobial peptides, but the most abundant proteins are core histones. Histones contained in NETs have been deiminated, and arginines are converted in citrullines. While deimination is a physiological process amplified in inflammatory conditions, only individuals carrying genetic predisposition to develop rheumatoid arthritis (RA) make antibodies to deiminated proteins. These antibodies, collectively identified as anti-citrullinated proteins/peptides antibodies (ACPA), react with different deiminated proteins and display partially overlapping specificities. In this paper, we will summarize current evidence supporting the role of NETosis as critical mechanism in the breach of tolerance to self-antigens and in supporting expansion and differentiation of autoreactive cells. In fact, several lines of evidence connect NETosis with RA: RA unstimulated synovial fluid neutrophils display enhanced NETosis; sera from RA patients with Felty’s syndrome bind deiminated H3 and NETs; a high number of RA sera bind deiminated H4 contained in NETs; human monoclonal antibodies generated from RA synovial B cells decorate NETs and bind deiminated histones. In RA, NETs represent on one side an important source of autoantigens bearing posttranslational modifications and fueling the production of ACPA. On the other side, NETs deliver signals that maintain an inflammatory milieu and contribute to the expansion and differentiation of ACPA-producing B cells. PMID:27895639

  4. Ultrasound-guided synovial biopsy

    PubMed Central

    Sitt, Jacqueline C M; Wong, Priscilla

    2016-01-01

    Ultrasound-guided needle biopsy of synovium is an increasingly performed procedure with a high diagnostic yield. In this review, we discuss the normal synovium, as well as the indications, technique, tissue handling and clinical applications of ultrasound-guided synovial biopsy. PMID:26581578

  5. A proinflammatory role for IL-18 in rheumatoid arthritis

    PubMed Central

    Gracie, J. Alastair; Forsey, Rosalyn J.; Chan, Woon Ling; Gilmour, Ashley; Leung, Bernard P.; Greer, Morag R.; Kennedy, Kristy; Carter, Robert; Wei, Xiao-Qing; Xu, Damo; Field, Max; Foulis, Alan; Liew, Foo Y.; McInnes, Iain B.

    1999-01-01

    IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-γ production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-α synthesis by CD14+ macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-α and IFN-γ synthesis was suppressed by IL-10 and TGF-β. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-α and IL-1β, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund’s adjuvant–immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA. J. Clin. Invest. 104:1393–1401 (1999). PMID:10562301

  6. 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

  7. 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.

  8. Bcl-2 expression in synovial fibroblasts is essential for maintaining mitochondrial homeostasis and cell viability.

    PubMed

    Perlman, H; Georganas, C; Pagliari, L J; Koch, A E; Haines, K; Pope, R M

    2000-05-15

    The regulation of proliferation and cell death is vital for homeostasis, but the mechanism that coordinately balances these events in rheumatoid arthritis (RA) remains largely unknown. In RA, the synovial lining thickens in part through increased proliferation and/or decreased synovial fibroblast cell death. Here we demonstrate that the anti-apoptotic protein, Bcl-2, is highly expressed in RA compared with osteoarthritis synovial tissues, particularly in the CD68-negative, fibroblast-like synoviocyte population. To determine the importance of endogenous Bcl-2, an adenoviral vector expressing a hammerhead ribozyme to Bcl-2 (Ad-Rbz-Bcl-2) mRNA was employed. Ad-Rbz-Bcl-2 infection resulted in reduced Bcl-2 expression and cell viability in synovial fibroblasts isolated from RA and osteoarthritis synovial tissues. In addition, Ad-Rbz-Bcl-2-induced mitochondrial permeability transition, cytochrome c release, activation of caspases 9 and 3, and DNA fragmentation. The general caspase inhibitor zVAD.fmk blocked caspase activation, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation, but not loss of transmembrane potential or viability, indicating that cell death was independent of caspase activation. Ectopically expressed Bcl-xL inhibited Ad-Rbz-Bcl-2-induced mitochondrial permeability transition and apoptosis in Ad-Rbz-Bcl-2-transduced cells. Thus, forced down-regulation of Bcl-2 does not induce a compensatory mechanism to prevent loss of mitochondrial integrity and cell death in human fibroblasts.

  9. Circulating CD4+CD161+ T Lymphocytes Are Increased in Seropositive Arthralgia Patients but Decreased in Patients with Newly Diagnosed Rheumatoid Arthritis

    PubMed Central

    Chalan, Paulina; Huitema, Minke G.; Abdulahad, Wayel H.; Bijzet, Johan; Brouwer, Elisabeth; Boots, Annemieke M. H.

    2013-01-01

    Improved understanding of the immune events discriminating between seropositive arthralgia and clinical synovitis is of key importance in rheumatology research. Ample evidence suggests a role for Th17 cells in rheumatoid arthritis. We hypothesized that CD4+CD161+ cells representing Th17 lineage cells may be modulated prior to or after development of clinical synovitis. Therefore, in a cross-sectional study, we investigated the occurrence of CD4+CD161+ T-cells in seropositive arthralgia patients who are at risk for developing rheumatoid arthritis and in newly diagnosed rheumatoid arthritis patients. In a prospective study, we evaluated the effect of methotrexate treatment on circulating CD4+CD161+ T-cells. Next, we assessed if these cells can be detected at the level of the RA joints. Precursor Th17 lineage cells bearing CD161 were found to be increased in seropositive arthralgia patients. In contrast, circulating CD4+CD161+T-cells were decreased in newly diagnosed rheumatoid arthritis patients. The decrease in CD4+CD161+ T-cells correlated inversely with C-reactive protein and with the 66 swollen joint count. Methotrexate treatment led to normalization of CD4+CD161+ T-cells and reduced disease activity. CD4+CD161+ T cells were readily detected in synovial tissues from both early and late-stage rheumatoid arthritis. In addition, synovial fluid from late-stage disease was found to be enriched for CD4+CD161+ T-cells. Notably, synovial fluid accumulated CD4+CD161+T-cells showed skewing towards the Th1 phenotype as evidenced by increased interferon-γ expression. The changes in peripheral numbers of CD4+CD161+ T-cells in seropositive arthralgia and early rheumatoid arthritis and the enrichment of these cells at the level of the joint predict a role for CD4+CD161+ T-cells in the early immune events leading to clinical synovitis. Our findings may add to the development of RA prediction models and provide opportunities for early intervention. PMID:24223933

  10. 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

  11. [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.

  12. 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.

  13. 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

  14. Joint histology in Alligator mississippiensis challenges the identification of synovial joints in fossil archosaurs and inferences of cranial kinesis.

    PubMed

    Bailleul, Alida M; Holliday, Casey M

    2017-03-29

    Archosaurs, like all vertebrates, have different types of joints that allow or restrict cranial kinesis, such as synovial joints and fibrous joints. In general, synovial joints are more kinetic than fibrous joints, because the former possess a fluid-filled cavity and articular cartilage that facilitate movement. Even though there is a considerable lack of data on the microstructure and the structure-function relationships in the joints of extant archosaurs, many functional inferences of cranial kinesis in fossil archosaurs have hinged on the assumption that elongated condylar joints are (i) synovial and/or (ii) kinetic. Cranial joint microstructure was investigated in an ontogenetic series of American alligators, Alligator mississippiensis All the presumably synovial, condylar joints found within the head of the American alligator (the jaw joint, otic joint and laterosphenoid-postorbital (LS-PO) joint) were studied by means of paraffin histology and undecalcified histology paired with micro-computed tomography data to better visualize three-dimensional morphology. Results show that among the three condylar joints of A. mississippiensis, the jaw joint was synovial as expected, but the otherwise immobile otic and LS-PO joints lacked a synovial cavity. Therefore, condylar morphology does not always imply the presence of a synovial articulation nor mobility. These findings reveal an undocumented diversity in the joint structure of alligators and show that crocodylians and birds build novel, kinetic cranial joints differently. This complicates accurate identification of synovial joints and functional inferences of cranial kinesis in fossil archosaurs and tetrapods in general.

  15. 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 ...

  16. IK acts as an immunoregulator of inflammatory arthritis by suppressing TH17 cell differentiation and macrophage activation

    PubMed Central

    Park, Hye-Lim; Lee, Sang-Myeong; Min, Jun-Ki; Moon, Su-Jin; Kim, Inki; Kang, Kyung-Won; Park, Sooho; Choi, SeulGi; Jung, Ha-Na; Lee, Dong-Hee; Nam, Jae-Hwan

    2017-01-01

    Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA. PMID:28071693

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Emerging MRI methods in rheumatoid arthritis.

    PubMed

    Borrero, Camilo G; Mountz, James M; Mountz, John D

    2011-02-01

    New MRI techniques have been developed to assess not only the static anatomy of synovial hyperplasia, bone changes and cartilage degradation in patients with rheumatoid arthritis (RA), but also the activity of the physiological events that cause these changes. This enables an estimation of the rate of change in the synovium, bone and cartilage as a result of disease activity or in response to therapy. Typical MRI signs of RA in the pre-erosive phase include synovitis, bone marrow edema and subchondral cyst formation. Synovitis can be assessed by T2-weighted imaging, dynamic contrast-enhanced MRI or diffusion tensor imaging. Bone marrow edema can be detected on fluid-sensitive sequences such as short-tau inversion recovery or T2-weighted fast-spin echo sequences. Detection of small bone erosions in the early erosive phase using T1-weighted MRI has sensitivity comparable to CT. Numerous MRI techniques have been developed for quantitative assessment of potentially pathologic changes in cartilage composition that occur before frank morphologic changes. In this Review, we summarize the advances and new directions in the field of MRI, with an emphasis on their current state of development and application in RA.

  2. Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging

    PubMed Central

    Gaffney, K.; Cookson, J.; Blades, S.; Coumbe, A.; Blake, D.

    1998-01-01

    OBJECTIVE—To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI).
METHODS—Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area).
RESULTS—Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement.
CONCLUSIONS—Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

 Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity PMID:9640130

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

    PubMed

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

    2017-01-01

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

  4. Aspergillus arthritis: analysis of clinical manifestations, diagnosis, and treatment of 31 reported 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; Henry, Michael; Petraitis, Vidmantas; Denning, David W; Lortholary, Olivier; Walsh, Thomas J

    2016-09-08

    Aspergillus arthritis is a debilitating form of invasive aspergillosis. Little is known about its epidemiology, clinical manifestations, laboratory features, treatment, and prognosis. Cases of Aspergillus arthritis were reviewed in the English literature from 1967 through 2015 for variables of arthritis with Aspergillus spp. recovered from joint and/or adjacent bone, underlying conditions, symptoms, signs, inflammatory biomarkers, diagnostic imaging, management, and outcome. Among 31 evaluable cases, 87% were males and 13% pediatric. Median age was 50 y (range 1-83 y). Seventeen (55%) patients were immunosuppressed with such conditions as hematological malignancies (26%), corticosteroids (39%), and/or transplantation (26%). Approximately one-half (52%) of patients had hematogenous seeding of the joint, and more than 80% had de novo infection with no prior antifungal therapy. Oligoarticular infection (2-3 joints) occurred in 45% and contiguous osteomyelitis was present in 61%. Clinical manifestations included pain (87%), edema (26%), and limited function (23%), with knees (35%), intervertebral discs (26%), and hips (16%) being most commonly infected. Aspergillus fumigatus constituted 77% of cases followed by Aspergillus flavus in 13%, Aspergillus niger in 3%, and not specified in 7%. Median ESR was 90 mm/hr and median CRP was 3.6 mg/dl. Median synovial fluid WBC was 17,200/μL (7,300-128,000) with 72% PMNs (range 61-92). Osteolysis occurred in 35%, and soft-tissue extension 47%. Nineteen patients (61%) were managed with combined medical and surgical therapy, 10 (32%) with medical therapy only, and 2 (6%) surgery only. Amphotericin B and itraconazole were the most frequently used agents with median duration of therapy of 219 days (range 30-545). Surgical interventions included debridement in 61%, drainage 19%, and amputation 6%. Complete or partial response was achieved in 71% and relapse occurred in 16%. Medical therapy was reinstituted with successful outcome in

  5. Therapeutic Opportunities to Prevent Post-Traumatic Arthritis: Lessons from the Natural History of Arthritis after Articular Fracture

    PubMed Central

    Olson, Steven A.; Furman, Bridgette D.; Kraus, Virginia B.; Huebne