Expression Of TPP1 And POT1 In Synovial Fibroblasts Of Patients With Rheumatoid Arthritis

Objective: To study the expression of telomeric protein TPP1 and POT1 and its association with disease stages and clinical manifestations in synovial fibroblasts (SFs) from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy individuals; to explore the role of TPP1 and POT1 in the pathogenesis of RA.Methods: 1. 42 RA patients, 23 OA patients and 3 healthy individuals were enrolled into the study. 2. The clinical data of RA patients and OA patients were collected. SFs from RA patients, OA patients and healthy individuals were cultured in vitro. 3. The TPP1 and POT1 mRNA of SFs were measured using RT-qPCR in RA, OA patients and healthy individuals, and the differences of genes expression in three groups were compared using the analysis of variance (ANOVA). The relationships between levels of telomeric genes and clinical data of RA were analyzed using Spearman's rank correlation test. 4. The levels of telomeric proteins TPP1 and POT1 were examined by Laser scanning Confocal Microscopy and Western blotting. The differences of proteins levels in three groups were compared and the relationships between levels of telomeric proteins and clinical data of RA were analyzed.Results: The expression of TPP1 and POT1 mRNA were significant reduced in RA patients compared with OA patients and healthy controls (TPP1:0.006±0.003 vs 0.179±0.077 vs 0.195±0.054, F= 115.9,P<0.05;POT1:0.008±0.003 vs 0.063±0.027 vs 0.073±0.011, F=107.3,P<0.05). Confocal immunofluorescene microscopy revealed that the telomeric proteins TPP1 and POT1 were both expressed in SFs and mainly located in cell nucleus; The level of TPP1 protein in RASFs was much lower than that in OA and healthy controls (0.225±0.018 vs 0.632±0.030 vs 0.657±0.046,F=499.9,P<0.05), no significant differences was found in POT1 protein. Significant negative relationships between level of mRNA TPP1 and the titer of rheumatoid factor, anti-CCP antibody were observed (P<0.05, respectively).Conclusion: Altered expression of telomeric gene and protein of TPP1 and POT1 might be involved in the pathogenesis of RA.