Effects of daphnetin combined with Bcl2‑siRNA on antiapoptotic genes in synovial fibroblasts of rats with collagen‑induced arthritis.

Abstract

The aim of the present study was to investigate the effects of daphnetin combined with B cell lymphoma 2 (Bcl2)‑targeted small interfering (si)RNA (si‑Bcl2) on antiapoptotic genes in fibroblast‑like synoviocytes (FLS) in rats with collagen II‑induced arthritis (CIA). The roles of si‑Bcl2 and daphnetin were determined by measuring the expression levels of Bcl2. Protein and mRNA expression levels of Bcl2 in FLS were determined by flow cytometry and reverse transcription‑quantitative polymerase chain reaction. Apoptosis of FLS was also determined by flow cytometry. It was revealed that treatment with si‑Bcl2 or daphnetin alone resulted in downregulation of Bcl2 mRNA and protein expression. In addition, the mRNA expression levels of the signal transducer and activator of transcription 3 (STAT3), which transcriptionally regulates the activity of mitochondria, were reduced. The combination of si‑Bcl2 and daphnetin exhibited an enhanced effect on rheumatoid arthritis FLS (RAFLS), in which the apoptotic rate was significantly higher than either treatment alone. The results suggested that si‑Bcl combined with daphnetin may have an enhanced effect in promoting apoptosis of RAFLS derived from CIA rats, and a possible underlying molecular mechanism may function through the downregulation of Bcl2 expression and STAT3, which is located upstream of Bcl2 in the mitochondrial apoptotic pathway. The results of the present study are expected to provide theoretical and experimental basis for the treatment of RA and the medicinal development of daphnetin combined siRNA.