Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
SOX5 is known as a transcription factor which primarily involved in in the regulation of embryonic development, cell fate, and chondrogenesis. To date, little is known the effect of SOX5 on rheumatoid arthritis (RA). We previously reported a RANKL promoter SNP confers an elevated promoter activity after stimulation via binding to a SOX family transcription factor SOX5 and is associated with younger age at onset of rheumatoid arthritis (RA) (Arthritis Rheum 2010; 62(10):2864-75.). Subsequently, we confirmed that SOX5 could up-regulate RANKL expression in RA synovial fibroblast(SF) and participate in the bone erosion of RA. Here, we examine the effect of SOX5 on the migration and invasive characteristics of RA synovial fibroblasts.
Rheumatoid synovial fibroblasts cell line MH7A were treated with SOX5 small interfering RNA (SOX5-siRNA) and recombinant Adenovirus SOX5 expression vectors (Ad-SOX5). Migration and invasion and of RASF was assessed by transwell matrigelTMinvasion chambers and collagen gel assays. Modulation of MMP9 expression in RASF was analyzed by real-time PCR, western blot and luciferase assay. Collagen-induced arthritis (CIA) DBA/1 mouse locally injected with lentivirus-shSOX5 was used to examine the effect of SOX5 on MMP9 expression in vivo.
Overexpression of SOX5 significantly promoted cell migration, invasion and MMP-9 expression in RASF. Migration and invasion of RASF was markedly decreased by silencing SOX5 expression in RASF but could be reverted by added the recombinant MMP9 cytokine into RASF. Overexpression of SOX5 enhanced the promoter activity of MMP9 in Hela cell. Local silencing SOX5 in CIA mice inhibited the synovitis and bone erosion and accompanied by the reduced MMP9 expression in synovium of CIA mice.
These findings indicate transcription factor SOX5 plays an important role in regulating RASF migration and invasion by modulation MMP9 expression, suggesting SOX5 as a potential therapeutic target for the treatment of RA.
To cite this abstract in AMA style:Tan W, Shi Y, Feng X, Wang F, Wang X, Peng Q, Xuan W, miaojia Z. Transcription Factor SOX5 Promotes Rheumatoid Arthritis Synovial Fibroblast Migration and Invasion By Regulating MMP9 Expression [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/transcription-factor-sox5-promotes-rheumatoid-arthritis-synovial-fibroblast-migration-and-invasion-by-regulating-mmp9-expression/. Accessed September 22, 2019.
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