title: [Effects of Dickkopf-1 on synovitis of rheumatoid arthritis].
abstract: OBJECTIVE
  As an important feature of rheumatoid arthritis (RA), an excessive amount of pro-inflammatory cytokines in RA synovial lesions induces the proliferation of synovial fibroblasts, cartilage erosion and systemic inflammatory immune response. Wnt inhibitor, Dkk-1, contributes to joint remodeling. This study was conducted to explore the role of Dkk-1 in the regulation of pro-inflammatory cytokine secretion.
  
  
  METHODS
  Rheumatoid arthritis synovial fibroblasts (RASF) were cultured from surgical synovial specimens and utilized at passages 4-8. For Dkk-1 silencing assay, Dkk-1-specific siRNA and control scrambled siRNA were transfected into RASF respectively. For Dkk-1 over-expression assay, Dkk-1 plasmid and control vector were transfected into RASFs respectively. Production of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8), were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) at pre- and post-transfection respectively. Differences between various groups were evaluated by Wilcoxon signed-rank test.
  
  
  RESULTS
  After a treatment of Dkk-1-specific siRNA, RASF exhibited decreased production of pro-inflammatory cytokines in association with down-regulated Dkk-1 levels while Dkk-1 over-expression could up-regulate the production of pro-inflammatory cytokines. The effects were marked when RAFS was activated by TNF-α and IL-1β after transfection.
  
  
  CONCLUSIONS
  Dkk-1 promotes the production of pro-inflammatory cytokines in RASF so as to exacerbate synovitis of RA. And targeting Dkk-1 may provide a novel therapeutic strategy for RA.
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Fanlei
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Yingni
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing 100044, China. Email: xuewulore@163.com.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002356:Cartilage; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007378:Interleukins; D060888:Real-Time Polymerase Chain Reaction; D013585:Synovitis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha