Underlying mechanism of Sirt1 on apoptosis and extracellular matrix degradation of osteoarthritis chondrocytes.

Abstract

The study investigated the effects and underlying mechanisms of silent information regulation of transcription1 (Sirt1) action on apoptosis in chondrocytes and degradation of the extracellular matrix. Cartilage tissue samples were derived from knee arthroplasty of patients with osteoarthritis (OA). The three groups were as follows: Control, resveratrol (Res) and Res+small interfering (si)RNA (Res+siRNA Sirt1). The level of Sirt1 protein expression significantly increased in the Res group (1.03±0.10) compared with the control (0.22±0.03) and Res+siRNA (0.18±0.01) groups (both P<0.05). Early and late stage cell apoptosis rates decreased in the Res group and increased in the Res+siRNA group (both P<0.05). B‑cell lymphoma2 (Bcl‑2) expression levels were upregulated and Bcl‑2‑associated X protein (Bax) expression levels were downregulated in the Res group compared with the control group. Protein expression levels of MMP1 and MMP13 and the phosphorylation levels of extracellular signal regulated kinase (ERK), c‑Jun N‑terminal kinase (JNK) and p38 were downregulated in the Res group and upregulated in the Res+siRNA group. In conclusion, upregulation of Sirt1 expression may inhibit OA chondrocyte apoptosis and extracellular matrix degradation by increasing Bcl‑2 expression and decreasing Bax, MMP1 and MMP13 expression, via downregulation of p38, JNK and ERK phosphorylation.