Expression and function of transcription factor RUNX2in synovial tissues of rheumatoid arthritis

摘要

Objective:This study aimed to explore the expression profile of transcription factor Runt-related transcription factor 2 (RUNX2)in the synovial tissues of rheumatoid arthritis (RA) and its effect on the apoptosis of RA fibroblast-like synovial cells (RA-FLS),and to screen new targets for the diagnosis,treatment and prognosis of RA.Methods:The expression and localization of mRNA and protein of RUNX2 in the synovial tissues were detected by real-time quantitative PCR (qPCR)and immunohistochemical staining,respectively.The effect of the expression of exogenous RUNX2 on the apoptosis process of RA-FLS cell line MH7A was investigated by flow cytometry,and the activation of NF-κB signaling pathway was detected by western blotting.Results:The expression of RUNX2 mRNA was significantly higher in the synovial tissues from RA patients,compared to that in the OA patients (P＜0.05).RUNX2 protein was mainly localized in the nuclear of the RA synovial cells.Overexpression of exogenous RUNX2 could notably decrease the apoptosis of RA-FLS,which was substantially reversed by pretreatment with SN50,a specific inhibitor of NF-κB pathway.Compared with blank group and negative control group (pCMV6-AC-GFP-vector),the apoptotic rate of exogenous RUNX2 overexpressing (pCMV6-AC-GFP-RUNX2) MH7A cells was significantly decreased (P＜0.05).NF-κB signaling pathway activity was significantly increased (P＜0.05),and this effect could be effectively reversed by NF-κB signal pathway-specific inhibitor SN5.Conclusion:The high expression of UNX2 in RA synoviocytes could significantly inhibit the spontaneous apoptosis of cells,and it was related to the abnormal activation of NF-κB signaling pathway.In-depth studies of RUNX2/NF-κB signaling pathways will help to identify novel therapeutic targets for RA.