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

Jun Lin,Yifan Wang,Ming Pei,Junxin Zhang,Jinku Yan,Guangdong Chen,Huilin Yang,Jia Yu,Xi Chen,Fan He,Caihong Zhu,Guoqing Pan,Tao Liu

doi:10.1155/2018/1368142

Abstract

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.

Highlights

Osteoarthritis (OA) is a chronic degenerative joint disease that is characterized by a gradual loss of cartilage, inflammation of the synovium, and subchondral bone changes
bone marrow-derived mesenchymal stem cells (BM-Medicine and Cellular Longevity stem cells (MSCs)) were treated with KGN at concentrations of 10−8 M, 10−7 M, and 10−6 M, and cell proliferation was tested on days 1, 3, 5, and 7
We examined the effect of KGN on intracellular reactive oxygen species (ROS) production in BM-MSCs (Figure 1(b))

Summary

Introduction

Osteoarthritis (OA) is a chronic degenerative joint disease that is characterized by a gradual loss of cartilage, inflammation of the synovium, and subchondral bone changes. OA is generally considered a cartilage disease, but increasing evidence suggests the involvement of subchondral bone in the initiation and progression of OA. It has been shown that subchondral bone can affect cartilage metabolism by transporting growth factors and cytokines [1]. A decreased trabecular spacing and reduced hardness of the bone has been reported in patients with OA [2]. OA is characterized by increased bone remodeling in the subchondral bone tissue, whereas a reduction in bone resorption occurs in late OA [3]. Bone remodeling involves two specialized cells, osteoclasts and osteoblasts. Osteoclasts originate from hematopoietic monocytes or macrophages and are responsible for bone resorption.

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