title: Altered expression of TPP1 in fibroblast-like synovial cells might be involved in the pathogenesis of rheumatoid arthritis.
abstract: We undertook this study to determine whether the altered expression of telomeric proteins TPP1 and POT1 in fibroblast-like synovial cells (FLS) could provide insights into the pathogenesis of rheumatoid arthritis (RA). FLS were isolated from patients with RA, osteoarthritis (OA) and traumatic joint disease, and cultured in vitro. TPP1 and POT1 mRNA level of FLS were measured using real-time quantitative polymerase chain reaction (RT-qPCR) in 42 RA, 23 OA and 13 healthy cases. Immunofluorescence staining and Western blot were used to detect the expression of TPP1 and POT1 protein. Expression of TPP1 and POT1 mRNA was significantly reduced in RA cases (P < 0.001, respectively), and no significant difference was observed between OA and healthy cases (P > 0.05, respectively). Confocal microscopy images showed TPP1 and POT1 proteins mainly located in nucleus of FLS. Western blot demonstrated that TPP1 protein level was significantly reduced in RA cases (P < 0.001), and POT1 protein expression was not statistical significance among RA, OA patients and healthy cases (P > 0.05). Significant negative correlation was observed between level of TPP1 mRNA and titers of anti-CCP antibody (P < 0.001), RF (P < 0.01). Altered expression of TPP1 might contribute to persistent proliferation of FLS in RA, further study on functions of telomeric proteins in RA would be needed.
authors.affiliation: Institute of Rheumatology and Immunology and Department of Rheumatology and Hematology, The Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Qing
authors.forename: Jing-Guo
authors.initials: JG
authors.lastname: Zhou
authors.forename: Ming-Cai
authors.initials: MC
authors.lastname: Zhao
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Xie
authors.forename: Qi-Bin
authors.initials: QB
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Zeng
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D002681:China; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010456:Peptides, Cyclic / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D000089804:Shelterin Complex; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C495876:ACD protein, human; D001323:Autoantibodies; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C487763:cyclic citrullinated peptide