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

Zheng Li; Muxin Yue; Xuenan Liu; Yunsong Liu; Longwei Lv; Ping Zhang; Yongsheng Zhou

Bioactive Materials (Dec 2022)

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

Zheng Li,
Muxin Yue,
Xuenan Liu,
Yunsong Liu,
Longwei Lv,
Ping Zhang,
Yongsheng Zhou

Affiliations

Zheng Li: 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
Muxin Yue: 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
Xuenan Liu: 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
Yunsong Liu: 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
Longwei Lv: 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
Ping Zhang: 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; Corresponding author. Vice Professor of Department of Prosthodontics, School and Hospital of Stomatology of Peking University, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China.
Yongsheng Zhou: 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; Corresponding author. President of School and Hospital of Stomatology of Peking University, Professor of Department of Prosthodontics, Vice-Director for National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Vice-Director for the National Clinical Research Center of Oral Diseases (PKU), 22 Zhongguancun South Avenue, Haidian District, Beijing, 10081, PR China.

Journal volume & issue: Vol. 18
pp. 492 – 506

Abstract

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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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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