title: Inhibition of microRNA-21 decreases the invasiveness of fibroblast-like synoviocytes in rheumatoid arthritis via TGFβ/Smads signaling pathway.
abstract: OBJECTIVE
  MicroRNA-21 (miR21) is aberrantly elevated in rheumatoid arthritis (RA) patients, the significance of this microRNA in RA pathogenesis and treatment, however, has not been investigated. In this study, by using RA-derived fibroblast-like synoviocyte (FLS) cells as a model, we investigated the effect and corresponding mechanism of miR21 inhibition on FLSs invasion.
  
  
  METHODS
  miR21 expression in synovial tissue and FLSs in RA patients and non-RA controls were determined by stem-loop RT-PCR. The effect of miR21 on FLSs viability and invasiveness were evaluated using miR21 inhibition. Cell viability was evaluated by MTT assay and the expression of genes at mRNA and protein levels was determined by RT-PCR and Western blot, respectively.
  
  
  RESULTS
  Our results showed that miR21 expression was highly increased in synovial tissue and FLSs in RA patients. Also, we reported that miR21 inhibitor treatment could significantly suppress the invasiveness of FLSs without affecting cell viability. The decreased FLSs invasion by miR21 inhibition was associated with down-regulated expression of matrix metalloproteinase (MMP)-1, MMP3, and MMP13. Further analysis revealed that miR21 inhibition could suppress the expression of TGFβ1 and Smad4, but promote that of Smad7. Moreover, suppression of FLS invasion and MMPs expression by miR21 treatment could be counteracted by additional TGFβ1 treatment.
  
  
  CONCLUSIONS
  Our results indicated that miR21 inhibition can down-regulate the expression of MMP1, MMP3, and MMP13 and consequently suppress the invasiveness of FLS, which is achieved through TGFβ1/Smad4/7 signaling pathway. The findings of this study could offer a novel approach for RA treatment.
authors.affiliation: Department of Orthopedics, The First People's Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
authors.forename: Gaoxin
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Orthopedics, The First People's Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, The First People's Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, The First People's Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Orthopedics, The First People's Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Orthopedics, The First People's Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
authors.forename: Shuangli
authors.initials: S
authors.lastname: Wang
keywords: Fibroblast-like synoviocyte; Invasion; MicroRNA-21; Rheumatoid arthritis; Smads; Transforming growth factor-beta