No abstract available.
Arthritis, Rheumatoid* ; Folic Acid* ; Metabolism* ; Methotrexate*

Interleukin (IL)-36 is a family of cytokines that belongs to the larger IL-1 superfamily. IL-36 agonist/antagonist binds to the interleukin-36 receptor involving in physiological inflammation regulation and pathogenesis of many inflammatory diseases. In inflammatory joint diseases, the expression of IL-36 changes, and some studies have initially explored the role of IL-36 in these diseases. In psoriatic arthritis, IL-36 signal mediates plasma cell and fibroblast-like synoviocyte crosstalk presenting IL-36 agonist/antagonist imbalance. In rheumatoid arthritis, IL-36 agonists induce fibroblast-like synoviocyte to produce pro-inflammatory factors, while IL-36 antagonist deficiency leads to lesion progression. In osteoarthritis, IL-36 agonists induce chondrocytes to produce catabolic enzymes and pro-inflammatory factors. This article reviews the expression and function of IL-36 in different inflammatory joint diseases to provide a reference for revealing their pathogenic mechanisms and discovering therapeutic targets.
Humans ; Interleukins ; Arthritis, Rheumatoid ; Osteoarthritis/pathology* ; Arthritis, Psoriatic/metabolism* ; Cytokines

Fractionation of protein components of the human synovial fluid was carried out with paper and disc electrophoresis, and isoelectric focusing. The mean ranges of total protein content of synovial fluid obtained in the thirty patients suffering from nonspecific and traumatic synovitis, degenerative osteoarthritis or rheumatoid arthritis were 3.8 to 4.6g/dl. There was no significant difference between each from of arthritis. The pattern of protein fractionation of synovial fluid by paper electrophoresis was similar to that of serum protein. On disc electrophoresis, 20 fractions were identified in synovial fluid and the main fraction was albumin. Isoelectric focusing of the human serum with Ampholine carrier ampholyte in thin layer polyacrylamide gel revealed 27 protein fractions and five isoenzymes of amylase and two of them were the main fractions. In the synovial fluid 22 protein fractions and two isoenzymes of amylase, which had the same isoelectric points as the main fractions of serum, were noted. It is suggested that the isoamylases in the synovial fluid are a dialysate of plasma enzymes.
Arthritis, Rheumatoid/metabolism ; Human ; Osteoarthritis/metabolism ; Proteins/metabolism* ; Synovial Fluid/metabolism* ; Synovitis/metabolism

OBJECTIVE: To detect receptor activator of nuclear factor kappa B ligand (RANKL) expressed on B10 cells in rheumatoid arthritis (RA) and to evaluate the correlation between RANKL-producing B10 cells in RA and clinical features and laboratory parameters, trying to reveal the possible role of B10 cells in the pathogenesis of RA and the potential mechanism of impaired immunosuppressive capacities. METHODS: 25 RA patients and 20 healthy volunteers were enrolled. These RA patients did not received treatment with glucocorticoids, disease-modifying anti-rheumatic drug and biologics during the recent half of a year. The levels of RANKL-producing B10 cells were measured by flow cytometry (FCM) and polymerase chain reaction (PCR). The correlation between the frequencies of RANKL-producing B10 cells in RA and clinical data, laboratory parameters were analyzed. The role of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in inducing RANKL expression in B10 cells was evaluated by in vitro stimulation assay. Independent samples t test, Pearson and Spearman correlation were used for statistical analysis. RESULTS: B10 cells were capable of producing RANKL at a low level in health controls. The frequencies of RANKL-producing B10 cells were markedly higher in RA patients than in health controls (3.65%±1.59% vs. 2.25%±0.68%, P<0.01). The frequencies of these cells correlated positively with RA tender joint counts, swollen joint counts and disease activity score in 28 joints (DAS28) (r=0.479, P=0.035; r=0.519, P=0.008; r=0.526, P=0.019). However, no correlation was found between these cells and RA patient age, disease duration, or the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). After in vitro stimulation by TNF-α, but not IL-1β, B10 cells isolated from healthy donors demonstrated fundamentally upregulated expression of RANKL. CONCLUSION Our studies showed the frequencies of RANKL-producing B10 cells were markedly higher in RA patients, and their frequencies were positively correlated with RA tender joint counts, swollen joint counts and DAS28. These findings suggested that B10 cells might be involved in RA bone destruction.
Antirheumatic Agents ; Arthritis, Rheumatoid/metabolism* ; Autoantibodies/metabolism* ; B-Lymphocytes, Regulatory/metabolism* ; Humans ; RANK Ligand/metabolism* ; Rheumatoid Factor

IL-32 acts as a pro-inflammatory cytokine by inducing the synthesis of inflammatory molecules as well as promoting the morphological changes involved in the transformation of monocytes into osteoclasts (OCs). Evaluation of the functions of IL-32 has mainly focused on its inflammatory properties, such as involvement in the pathogenesis of various autoimmune diseases. Recently, IL-32 was shown to be involved in bone metabolism, in which it promotes the differentiation and activation of OCs and plays a key role in bone resorption in inflammatory conditions. IL-32γ also regulates bone formation in conditions such as ankylosing spondylitis and osteoporosis. In this review, we summarize the results of recent studies on the role of IL-32γ in bone metabolism in inflammatory arthritis.
Arthritis* ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Bone Resorption ; Inflammation ; Metabolism* ; Monocytes ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Osteoporosis ; Spondylitis, Ankylosing

OBJECTIVES: Mutation of p53 may play a role in manifestation of rheumatoid arthritis synovium, but several studies on p53 expression in synovial tissues of rheumatoid arthritis showed conflicting results. We investigated the amount and pattern of p53 positive cells in rheumatoid arthritis synovium, in comparison with osteoarthritis synovium, by using immunohistochemistry with two other monoclonal antibodies for p53. METHODS: Synovial tissues from 9 patients with rheumatoid arthritis and 5 patients with osteoarthritis were examined for p53 expression by immunohistochemistry with 2 monoclonal antibodies for p53, DO-1 and DO-7. Histologic features of inflammation were also scored and compared with p53 expression. RESULTS: There was no significant difference between inflammatory scores in both groups. In the synovial tissues of rheumatoid arthritis patients, p53 positive cells were detected in 3 out of 9 samples(33%) and p53 expressions were restricted to inflammatory mononuclear cells, but synovial lining cells, subsynovial fibroblast-like cells and vascular endothelial cells were p53 negative. p53 expressions in osteoarthritis synovial tissues as control were observed in 2 out of 5 samples(40%) and the amount and pattern of p53 positive cells were comparable to those seen in rheumatoid arthritis synovial tissues. There was no demonstrable correlation between the synovial tissues of both groups with respect to inflammation scores and expression of p53 protein. CONCLUSION: Our findings suggest that altered p53 expression may not play a significant role in the manifestation of rheumatoid arthritis synovium. However these data need to be strengthened by increasing the number of samples and molecular biology approaches.
Arthritis, Rheumatoid/metabolism* ; Arthritis, Rheumatoid/genetics ; Comparative Study ; Gene Expression ; Genes, p53 ; Human ; Immunohistochemistry ; Osteoarthritis/metabolism ; Osteoarthritis/genetics ; Protein p53/metabolism* ; Protein p53/genetics ; Synovial Membrane/metabolism

This study proposed an assessment of the correlation of hand bone mineral density measured by dual energy x-ray absorbtiometry (DXA) with the carpo:metacarpal (C:MC) ratio and metacarpal cortical index (CI) in patients with rheumatoid arthritis (RA). The correlation of total hand BMD, CI and C:MC ratio with BMD at other sites, the Health Assessment Questionnaire (HAQ) and Larsen scores were also examined. The hand and axial BMD of 30 female patients were also compared with 29 age-matched healthy female controls. Total hand BMD values of patients were significantly lower than the control group. There was no significant difference between groups in axial measurements. CI correlated moderately with the second metacap (II.MC) midshaft and total hand BMD. The C:MC ratio correlated with II.MC midshaft and total hand BMD. Total hand BMD correlated moderately with the AP spine (L2-L4) and femoral neck BMD. Larsen scores showed weak negative correlation with II.MC midshaft BMD and CI. Grip strength correlated weakly only with total hand BMD. The results indicated that CI may reflect cortical bone mass of the hand accurately and did not predict bone density of the spine or hip in patients with RA. The C:MC ratio is a useful method for evaluating progression of wrist involvement and may be related to the loss of hand bone mineral density associated with disease process.
Adult ; Aged ; Arthritis, Rheumatoid/metabolism* ; Bone Density* ; Female ; Hand* ; Human ; Metacarpus/metabolism* ; Middle Age

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint swelling and progressive destruction of cartilage and bone. Current RA treatments are largely empirical in origin and their precise mechanism of action is uncertain. Increasing evidence shows that chronic inflammatory diseases such as RA are caused by prolonged production of proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin 1 (IL-1). The nuclear factor kappaB (NF-kappaB) plays an essential role in transcriptional activation of TNF and IL-1. NF-kappaB is induced by many stimuli including TNF and IL-1, forming a positive regulatory cycle that may amplify and maintain RA disease process. NF-kappaB and enzymes involved in its activation can be a target for anti-inflammatory treatment. Aspirin and sodium salicylate inhibit activation of NF-KB by blocking IkappaB kinase, a key enzyme in NF-kappaB activation. Glucocorticoids suppress expression of inflammatory genes by binding glucocorticoid receptor with NF-kappaB, and increasing expression of inhibitory protein of NF-kappaB, IkappaBalpha. Sulfasalazine and gold compounds also inhibit NF-kappaB activation. Continuing advances in our understanding of action mechanism of antirheumatic agents will benefit the future development of RA regimens with greater efficacy and less toxicity.
Animal ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/therapy* ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/immunology ; Cytokines/immunology ; Cytokines/genetics ; Gene Expression Regulation ; Human ; Macrophages/immunology ; NF-kappa B/metabolism* ; NF-kappa B/immunology ; NF-kappa B/biosynthesis ; Tumor Necrosis Factor/genetics

A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen (HLA)-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.
Adult ; Arthritis, Rheumatoid ; diagnosis ; metabolism ; Female ; HLA-B27 Antigen ; metabolism ; HLA-DR4 Antigen ; metabolism ; Humans ; Spondylitis, Ankylosing ; diagnosis ; metabolism

Methotrexate (MTX) is a widely used immunosuppressive drug. Large-dose of MTX is used for the treatment of cancer while low-dose is used for the treatment of rheumatoid arthritis (RA). This study aimed to explore the effect of MTX on the urinary proteome of rats. MTX was given to rats orally to construct an MTX intragastric administration rat model. The urine of the rats were collected within 10 hours after giving MTX, and the urine proteins of the rats were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 31 differential proteins were identified, of which 7 proteins were related to the effect MTX and the symptom of RA. The biological processes of some rats reflected the effect of MTX on the body's glutathione metabolism and the JAK/STAT signaling pathway, which indicated that urine proteins have the ability to reflect the effects of MTX on the body of rats. The spectrum of the differential proteins of each single rat showed that different individuals respond to the drug quite differently.
Rats ; Animals ; Methotrexate/metabolism* ; Proteome ; Chromatography, Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Arthritis, Rheumatoid/drug therapy*