Upregulation of SIRT1 by Kartogenin Enhances Antioxidant Functions and Promotes Osteogenesis in Human Mesenchymal Stem Cells

Abstract EN

Osteoarthritis is a chronic degenerative joint disease involving both articular cartilage and subchondral bone.

Kartogenin (KGN) was recently identified to improve in vivo cartilage repair; however, its effect on bone formation is unknown.

The aim of this study was to investigate the effect of KGN on antioxidant properties and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs).

Human BM-MSCs were treated with KGN at concentrations ranging from 10−8 M to 10−6 M.

Our results indicated that KGN improved cell proliferation and attenuated intracellular reactive oxygen species.

The levels of antioxidant enzymes and osteogenic differentiation of BM-MSCs were enhanced by KGN in a dose-dependent manner.

Furthermore, KGN-treated BM-MSCs showed upregulation of silent information regulator type 1 (SIRT1) and increased phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK), indicating that KGN activated the AMPK-SIRT1 signaling pathway in BM-MSCs.

Inhibition of SIRT1 by nicotinamide reversed the antioxidant effect of KGN on BM-MSCs and suppressed osteogenic differentiation.

In conclusion, our results demonstrated that KGN improved intracellular antioxidant properties and promoted osteogenic differentiation of BM-MSCs by activating the AMPK-SIRT1 signaling pathway.

Thus, KGN may have the potential for not only articular cartilage repair but also the clinical application of MSCs in bone tissue engineering.