Taurochenodeoxycholic acid induces apoptosis of fibroblast-like synoviocytes.

Recent evidences have suggested that the paucity of the apoptosis of fibroblast-like synoviocytes (FLS) may contribute to the pathogenesis of rheumatoid arthritis. Apoptosis induction of rheumatoid arthritis FLS is therefore suggested as a potential therapeutic approach for rheumatoid arthritis. Taurochenodeoxycholic acid (TCDCA), one of the main bioactive substances of animals' bile acid, could favorably ameliorate the progression development and bone destruction of adjuvant arthritis in rat. In this study, we aimed to investigate the possible effect of TCDCA on apoptosis induction of adjuvant arthritis FLS and the mechanisms involved in this process. Apoptosis was determined by flow cytometric analysis. Gene expression levels and the activities of caspase-3 and caspase-8 were evaluated using real time RT-PCR and luminogenic substrates. The activity of nuclear factor-κB (NF-κB) was measured by ELISA. The results showed TCDCA significantly enhanced the apoptosis of adjuvant arthritis FLS in a dose-dependent manner. Besides, TCDCA treatment markedly increased the gene expression level and activity of both caspase-3 and caspase-8. It could suppress the DNA-biding activity of NF-κB. We concluded TCDCA represented an apoptotic effect on adjuvant arthritis FLS via the activation of caspase cascade and this process may be mediated by NF-κB signaling pathway. It was suggested that TCDCA may be a potential therapeutic agent for rheumatoid arthritis.