Sirt7 protects chondrocytes degeneration in osteoarthritis via autophagy activation

Osteoarthritis (OA) is associated with decreased autophagy activity and imbalance of cell homeostasis in chondrocytes (CHs). Sirtuin 7 (Sirt7) is claimed to have the ability to activate the autophagy response. The aim of this study was to explore the function of Sirt7 in the development of OA involving autophagy by culturing human chondrocytes (CHs).

We collected knee joint cartilage from patients undergoing traumatic amputation and arthroscopic knee replacement. Protein and mRNA levels of collagen II, Sirt7, ULK1, Lc3, and Beclin1 were analyzed by Western blot and RT-PCR. CHs were isolated from the traumatic cartilage as a control group, and IL-1β was used to induce CHs degeneration. The expression of Sirt7 gene was silenced by siRNA and upregulated by recombinant human Sirt7 protein (rh-Sirt7). An autophagy activator Tat-beclin 1 (Tat) was used to activate autophagy in cultural CHs. Expression of collagen II, Sirt7, ULK1, Lc3, and Beclin1 was determined by immunofluorescence, Western blot, and RT-PCR, respectively.

The protein and mRNA levels of Collagen II, Sirt7, ULK1, Lc3-II, and Beclin1 expressions were decreased in OA cartilage compared with those in healthy cartilage. IL-1β degenerated the CHs resulting in a reduction of collagen II, which also downregulated Sirt7, ULK1, Lc3-II, and Beclin1. Sirt7 deficiency accelerated the catabolism of collagen II and weakened the expression of ULK1, Lc3-II, and Beclin1. On the contrary, exogenous rh-Sirt7 played a positive role in these gene expressions. Finally, Tat alleviated the CHs degeneration by upregulating collagen II and activating ULK1, Lc3-II, and Beclin1, but incapable to mediate Sirt7 expression.

Overall, these findings suggested that Sirt7 was suppressed in the degenerated cartilage. Sirt7 deficiency does harm to the autophagy level, affecting CHs metabolism, while the upregulation of Sirt7 activated autophagy and protected CHs degeneration. An appropriate increase in autophagy can protect CHs but has no effect on Sirt7 expression.