Extracellular matrix stiffness as an energy metabolism regulator drives osteogenic differentiation in mesenchymal stem cells  

作　　者：Jing Na Zhijie Yang Qiusheng Shi Chiyu Li Yu Liu Yaxin Song Xinyang Li Lisha Zheng Yubo Fan 

机构地区：[1]Key Laboratory of Biomechanics and Mechanobiology(Beihang University),Ministry of Education,Beijing Advanced Innovation Center for Biomedical Engineering,School of Biological Science and Medical Engineering,Beihang University,Beijing,100083,China

出　　处：《Bioactive Materials》2024年第5期549-563,共15页生物活性材料（英文）

基　　金：supported by National Natural Science Foundation of China[grant numbers 32171310,11972067,U20A20390,11827803,12332019].

摘　　要：The biophysical factors of biomaterials such as their stiffness regulate stem cell differentiation.Energy metabolism has been revealed an essential role in stem cell lineage commitment.However,whether and how extracellular matrix(ECM)stiffness regulates energy metabolism to determine stem cell differentiation is less known.Here,the study reveals that stiff ECM promotes glycolysis,oxidative phosphorylation,and enhances antioxidant defense system during osteogenic differentiation in MSCs.Stiff ECM increases mitochondrial fusion by enhancing mitofusin 1 and 2 expression and inhibiting the dynamin-related protein 1 activity,which contributes to osteogenesis.Yes-associated protein(YAP)impacts glycolysis,glutamine metabolism,mitochondrial dynamics,and mitochondrial biosynthesis to regulate stiffness-mediated osteogenic differentiation.Furthermore,glycolysis in turn regulates YAP activity through the cytoskeletal tension-mediated deformation of nuclei.Overall,our findings suggest that YAP is an important mechanotransducer to integrate ECM mechanical cues and energy metabolic signaling to affect the fate of MSCs.This offers valuable guidance to improve the scaffold design for bone tissue engineering constructs.

关 键 词：Matrix stiffness Metabolic regulation YAP Stem cell fate Cellular mechanics 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]