The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis

查看全文 作　　者：Zheng [1]Li;Muxin [1]Yue;Xuenan [1]Liu;Yunsong [1]Liu;Longwei [1]Lv;Ping [1]Zhang;Yongsheng [1]Zhou

机构地区：[1]Department of Prosthodontics,Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&Beijing Key Laboratory of Digital Stomatology,22 Zhongguancun South Avenue,Haidian District,Beijing,100081,PR China

出　　处：《Bioactive Materials》索引2022年第7卷第12期,共15页

基　　金：National Natural Science Foundation of China(81870742,81970911);Beijing Natural Science Foundation(7202233);Key Project of the National Natural Science Foundation of China(81930026);Project funded by China Postdoctoral Science Foundation(2020TQ0020,2021M700280);Research Foundation of Peking University School and Hospital of Stomatology(PKUSS20210102).We thank Dr.Siying Qin at the National Center for Protein Science at Peking University for technical assistance in AFM operation and data analysis,Dr.Yiqun Liu and Pengyuan Dong at the National Center for Protein Science and Core Facilities of Life Sciences in Peking University for technical assistance in SEM sample preparation,operation,and Xiaorui Hao at Electron Microscopy Laboratory at Peking University for bone sample preparation for AFM measurements.The image acquisition of confocal microscope was supported by Biological Imaging and Analysis Laboratory,Medical and Health Analytical Center,Peking University,especially Jing Wu.We appreciate Rong Guo of Beijing Cnkingbio Biotechnology Co.LTD for the bioinformatics assistance. 摘　　要：Understanding mechanisms underlying the heterogeneity of multipotent stem cells offers invaluable insights into biogenesis and tissue development. Extracellular matrix (ECM) stiffness has been acknowledged as a crucial factor regulating stem cell fate. However, how cells sense stiffness cues and adapt their metabolism activity is still unknown. Here we report the novel role of mitochondrial phosphoenolpyruvate carboxykinase (PCK2) in enhancing osteogenesis in 3D ECM via glycolysis. We experimentally mimicked the physical characteristics of 3D trabeculae network of normal and osteoporotic bone with different microstructure and stiffness, observing that PCK2 promotes osteogenesis in 3D ECM with tunable stiffness in vitro and in vivo. Mechanistically, PCK2 enhances the rate-limiting metabolic enzyme pallet isoform phosphofructokinase (PFKP) in 3D ECM, and further activates AKT/extracellular signal-regulated kinase 1/2 (ERK1/2) cascades, which directly regulates osteogenic differentiation of MSCs. Collectively, our findings implicate an intricate crosstalk between cell mechanics and metabolism, and provide new perspectives for strategies of osteoporosis. 关键词：OSTEOGENESIS Osteoporosis Extracellular matrix STIFFNESS PCK2 Mesenchymal stem cells

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The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis

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