Silent Information Regulator 2 Related Enzyme 1 Regulates Autophagy And Apoptosis Of Osteochondrocytes Through Mtor/Pi3k/Akt Signaling

Osteochondrocyte autophagy and apoptosis participates in osteoarthritis. Silent information regulator 2 related enzyme 1 (SIRT1) regulates cell differentiation, aging, and apoptosis. However, whether SIRT1 plays a role in autophagy and apoptosis of osteochondral cells is unknown. Cartilage tissue from OA patients and normal bone and joints were collected to detect SIRT1 level by Real-time PCR. Chondrocytes from OA patients were isolated and assigned into control group, si-SIRT1 group, and SIRT1 group followed by analysis of cell proliferation by MTT assay, Caspase 3 activity, expression of Bax, Bcl-2, ATG5 and Beclin1 by Real time PCR, and mTOR/PI3K/AKT expression by Western blot. SIRT1 was significantly upregulated in OA patients compared to controls (P < 0.05). Transfection of SIRT1 siRNA into OA chondrocytes can significantly down-regulate SIRT1, promote cell proliferation, decrease Caspase 3 activity and Bax expression, increase Bcl-2, ATG5 and Beclin1 expression, and elevate mTOR and pAKT expression (P < 0.05). pcDNA3.1-SIRT1 plasmid transfection into OA chondrocytes significantly up-regulated SIRT1 and reversed above changes (P < 0.05). SIRT1 expression is increased in OA patients. Down-regulating SIRT1 can inhibit the apoptosis of articular chondrocytes, promote autophagy and chondrocyte proliferation and inhibit arthritis by down-regulating mTOR/PI3K/AKT signaling pathway.