Rheumatoid arthritis: still a chronic disease

Department of Clinical Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit, University of Lyon, Edouard Herriot Hospital, Lyon 69437, France. Electronic address: .
The Lancet (Impact Factor: 39.21). 01/2013; 381(9870). DOI: 10.1016/S0140-6736(12)62192-8
Source: PubMed
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    ABSTRACT: Cysteine‑rich angiogenic inducer 61 (Cyr61) is a novel molecule that has been shown to be increased in the synovial tissues of patients with rheumatoid arthritis (RA). The present study was conducted in order to investigate the role of Cyr61 in the pathogenesis of RA. A human genome‑wide gene assay was used to screen gene expression in synovial tissues obtained from four patients with RA and three patients with osteoarthritis (OA). To examine the role of Cyr61 in the phenotype of RA‑fibroblast‑like synovial (FLS) cells, Cyr61 expression in RA‑FLS cells was knocked down using small interfering RNA (siRNA). Normal FLS cells transduced with lentiviral vectors encoding Cyr61 cDNA were used to further explore the effects of this molecule on FLS cell apoptosis, proliferation and invasion. The study found that the Cyr61 gene was highly expressed in the synovial cells from patients with RA compared with those from patients with OA. Downregulation of Cyr61 by siRNA led to impaired cell proliferation and invasion. Furthermore, it decreased the levels of matrix metalloproteinase (MMP)‑3 and MMP‑13, and induced apoptosis in RA‑FLS cells. Conversely, overexpression of Cyr61 in normal FLS cells led to opposite effects. In conclusion, these results indicate that Cyr61 is capable of promoting RA‑FLS cell proliferation and invasion via the suppression of apoptosis and the regulation of MMP expression. Therefore, Cyr61 may be a good target molecule for the treatment and prevention of RA.
    Molecular Medicine Reports 10/2014; DOI:10.3892/mmr.2014.2770 · 1.48 Impact Factor
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    ABSTRACT: Musculoskeletal pain, a major public health problem, is understudied pre-clinically.•Local intramuscular injections of acidified saline model facets of musculoskeletal pain.•IL-1 and IL-6, but not TNF, increase in muscle after injection of acidified saline.•Inhibiting NFκB in muscle blocks allodynia after acidified saline injection.•IL-1 receptor KO mice and IL-6 KO mice do not develop allodynia in this model.
    Brain Behavior and Immunity 10/2014; DOI:10.1016/j.bbi.2014.10.009 · 6.13 Impact Factor
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    ABSTRACT: Lycopodiastrum casuarinoides is a folk medicine used to treat inflammation-associated diseases including rheumatoid arthritis in South China. Since the major secondary metabolites in Lycopodiastrum casuarinoides are alkaloids, the present study aims to investigate the suppressive effects of total alkaloids of Lycopodiastrum casuarinoides (ALC) on adjuvant-induced arthritis (AA) in rats.Materials and methodsAA was induced (day 0) in male Sprague–Dawley rats by intradermal injection of complete Freund׳s adjuvant (CFA) in right hind footpad. Diclofenac sodium (SD) was chosen as the positive drug. SD (10 mg/kg) and ALC (20 and 40 mg/kg) administration started from day 1 and continued for 28 days. Paw swelling, arthritis scores, and histopathological changes were evaluated. In addition, the serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as cyclooxygenase-2 (COX-2) and nuclear factor (NF)-κB expressions in joint synovial tissues were detected.ResultsALC administration significantly suppressed the inflammatory responses in the joints of AA rats. It also decreased the serum levels of TNF-α, IL-6 and PGE2. Moreover, Western blot analysis showed that COX-2 and NF-κB expressions in synovial tissues of AA rats were significantly reduced.Conclusion These results indicated that ALC prevented the pathological development of AA in rats. ALC may be a potential candidate for the treatment of inflammation and arthritis.
    Journal of Ethnopharmacology 11/2014; DOI:10.1016/j.jep.2014.11.005 · 2.94 Impact Factor