Rheumatoid Arthritis Gene Expression Profile Of Adiponectin, Adiponectin Receptor Gene In The Pathogenesis Of Significance

Rheumatoid arthritis (RA) is one of the most common autoimmunediseases and is characterized by symmetrical erosive synovitis that may resultin progressive joint destruction and significant work disability. Thepathogenesis of RA remains incompletely understood, and there continues tobe a compelling need for increase the understanding of the mechanismsinvolved in these diseases, and consequently to identify novel diagnostic andtherapeutic targets for more effective diagnosis and therapies.Part 1 Microarray Analyses Gene Expression Profiles inRheumatoid arthritisObjectiveTo study gene expression profiles in peripheral blood mononuclear cells(PBMC) of rheumatoid arthritis by microarray analysis.MethodsTotal RNA was extracted from PBMC of 10 patients with active RA and3 age-and sex-matched control subjects. Used Illumina oligonucleotidemicroarray to characterize 48,000 gene expression profile of each sample.Microarray-based data for a subset of genes were validated using RT- PCRanalysis.ResultsIt is found 122 up-regulated genes and 29 down-regulated genes werefound in RA compared with those in control subjects (fold change＞2.0). Molecular and biological function analyses showed that the majority of theupregulated genes were associated with protein binding, translation control,transcriptional factors, metabolism, signal transduction, cell cycle, cellapoptosis, etc.ConclusionThese findings are expected to improve molecular mechanismunderstanding and the identification of therapeutic targets.Part 2 The Expression of Adiponectin and its Receptor inRheumatoid ArthritisObjectiveTo investigate the expression and the role of adiponectin and its receptorsin the pathogenesis of RA.MethodsReal-time PCR, Western blot, Immunohistochemistry, primary culture offibroblasts, ELISA and animal model were employed.Results1. Real-time PCR showed that adiponectin and adipoR1, but notadipoR2 mRNA expression was significantly upregulated in both PBMC andsynovium of patients with RA in comparison with osteoarthritis (OA) andhealthy controls (HC).2. Western blot analysis showed that more adiponectin and adipoR1were expressed in the synovium from RA than those of from OA.Immunohistochemistry analysis showed that numerous cells in the synovialsections from the patients with RA and OA expressed adipoR1, adipoR2 andadiponectin. Double labeling immunohistochemical technique showed that adiponectin was co-localized in fibroblasts.3. It was observed that approximately twice more adiponectin in thesynovial fluids of patients with RA than with OA. It appeared also thatthere were 16.6, 103, 27, 6.1 and 2.0 fold more IL-1β, IL-6, IL-8, TNFαandMCP-1 respectively in the synovial fluids of patients with RA than with OA.4. Adiponectin induced up to 8.1 and 11.4 fold increase in the releaseof MCP-1 and IL-6 from human synovial fibroblasts, respectively following24h incubation.5. Adiponectin can induce inflammation infiltration in joint cavityand synovium tissues when be injected to rat joint cavity.ConclusionAdiponectin and its receptors are likely to contribute to the formation ofinflamed joints in RA.