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The presence of antibodies to cyclic citrullinated peptide (CCP) has high specificity in the diagnosis of rheumatoid arthritis (RA). Hepatitis C virus (HCV) infection may induce extra-hepatic manifestations, such as polyarthritis that mimic RA. The aim of this study was to determine the prevalence of anti-CCP antibodies in HCV-infected patients with or without arthritis, rheumatoid factor (RF), or cryoglobulinemia and to investigate whether anti-CCP antibodies may be helpful in discriminating patients with RA from patients with HCV-associated arthropathy. A total of 44 patients with RA, 34 patients with HCV infections, and 42 control patients with non-RA rheumatic diseases were recruited for the study. Anti-CCP antibody levels were determined by enzyme-linked immunosorbent assay. We found that, consistent with other reports, patients with RA were more likely to have high titers of anti-CCP antibody than HCV-infected or control patients. A significant number of HCV-infected patients with neither RF nor cryoglobulinemia were also positive for anti-CCP antibodies (the three positive values were 36.10, 8.65, and 5.83 U/ml, P < 0.01 compared with the control patients). The presence of cryoglobulinemia and/or RF in HCV-infected patients did not affect the anti-CCP outcomes. Although anti-CCP antibodies remain to be a very useful tool in discriminating RA from non-RA, HCV-infected patients with neither RF nor cryoglobulinemia may have anti-CCP antibodies. Because of limited patient numbers, this tentative conclusion may need further confirmation with inclusion of more patient population.

Purpose: Using receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation on RAW264.7 as a screening tool; we synthesize and identify small-molecule inhibitors preserving immunomodulatory effects as therapeutics for rheumatoid arthritis. Methods: Differentiation into osteoclast-like cells was examined by tartrate-resistant acid phosphatase (TRAP) staining and expression of osteoclast differentiation markers. Collagen-induced arthritis (CIA) mice were administered test articles by gavages to assess its efficacy. Then clinical, histological, and biochemical parameters were assessed to determine the effects of N-(4-chloro-2-fluorophenyl)-2-hydroxybenzamide (NDMC101) on synovial inflammation and bone erosion by hematoxlin and eosin staining and Enzyme-linked immunosorbent assay (ELISA). Results: NDMC101 markedly inhibited RANKL-induced formation of TRAP+ multinucleated cells in RAW264.7 and bone marrow macrophage cells (BMMs). Moreover, pit formation assay showed that NDMC101 significantly reduced the bone-resorbing activity of mature osteoclasts. In CIA mice, oral administration of NDMC101 reduced arthritic index and mitigated bone erosion. Serum TNF-α and IL-1β concentrations in these mice were decreased significantly at the higher dose of 62.5 mg/kg. Conclusions: Screening of our chemical library, our findings suggest that NDMC101 inhibits osteoclastogenesis which also ameliorates paw swelling and inflammatory bone destruction. Its efficacy is associated with the inhibition of such transcription factors as NF-κB and NFATc1 as well as multiple protein kinases, including p38, ERK, and JNK. There results guarantee further clinical tests of NDMC101 for its therapeutic potential in the treatment of inflammation-induced bone diseases. [ABSTRACT FROM AUTHOR]

Background/purpose: Antibodies against type II collagen (anti-CII) are arthritogenic and central to the initiation of the disease. An animal model of collagen type II-specific monoclonal antibody-induced arthritis (CAIA) has been used for the evaluation of various therapeutic effects in rheumatoid arthritis (RA). We aimed to measure the expression of matrix metalloproteinase (MMP)-9 (gelatinase B), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in the acute and chronic stages of the CAIA model for application as a therapeutic marker.Methods: A commercially available antibody cocktail containing four monoclonal anti-type II collagen antibodies were injected into 6 to 8-week-old male BALB/c mice (n=20) and 50 microL lipopolysaccharide was injected 3 days later. The clinical manifestations of RA were recorded and scored at 10 days (acute stage) and 21 days (chronic stage). Then the mice were sacrificed for histologic analysis of the inflamed footpad and gene expression of IL-1beta, TNF-alpha and MMP-9 by ELISA and quantitative polymerase chain reaction amplification.Results: Marked inflammation was found in the limb joints of mice at 10 days. Both IL-1beta and MMP-9 expression played a central role in the inflammatory reaction in the acute stage. The expression level of MMP-9 mRNA remained high in the chronic stage of CAIA, but that of IL-1beta mRNA was unexpectedly negligible; the serum level of TNF-alpha in CAIA was undetectable in the acute stage. The expression level of TNF-alpha mRNA was also lower than IL-1beta and MMP-9 in the acute inflammatory stage.Conclusion: The CAIA model is a fast and highly replicable model of RA. MMP-9 and IL-1beta were highly expressed in the acute stage of CAIA. It is suggested the MMP-9 mRNA level is a suitable marker for both acute and chronic stage, whereas IL-1beta is a marker only for the acute stage of the CAIA murine model. [ABSTRACT FROM AUTHOR]

Adult-onset Still’s disease (AOSD) is an inflammatory disorder characterized by high-spiking fever, arthritis, and an evanescent rash. The pattern of chronic arthritis is a universal feature of AOSD. However, chronic bursitis with the formation of numerous rice bodies is a very rare presentation in a patient with AOSD. To our knowledge, no case of formation of numerous rice bodies in AOSD has been reported thus far. We describe the case of a 28-year-old man with AOSD with rice bodies in his left shoulder joint. [ABSTRACT FROM AUTHOR]

Abstract: To demonstrate the therapeutic potential for cartilage repair of mesenchymal stem cells derived from human umbilical cord (HUCSC), we studied the clinical and histopathological effects of intra-articular injection of HUCSCs in a collagen-induced arthritis (CIA) model. In our study, intra-articular injection of HUCSCs had no benefit in CIA mice; and accelerated the progression of arthritis in the presence of TNF-α. To determine the role of TNF-α, we injected the combination with HUCSCs and TNF inhibitor, showed reduced the disease signs in CIA mice. On exposure of TNF-α, stem cells significantly decreased the expression of CD90, HLA-G, and the levels of IL-10 in vitro and in vivo. Our data showed that TNF-α blocks the immunosuppressive effects of HUCSCs and that inhibition of TNF-α decreases cartilage destruction by suppressing the immunogenicity of HUCSCs. Injecting both a TNF inhibitor and HUCSCs may be a potential effective therapy for ameliorating the disease. [Copyright &y& Elsevier]