Research Paper Volume 12, Issue 4 pp 3976—3992
PKM2 suppresses osteogenesis and facilitates adipogenesis by regulating β-catenin signaling and mitochondrial fusion and fission
- 1 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2 Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
received: October 13, 2019 ; accepted: February 4, 2020 ; published: February 25, 2020 ;https://doi.org/10.18632/aging.102866
How to Cite
Copyright © 2020 Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Bone marrow mesenchymal stem cells (BMSCs) differentiation dysfunction is a common pathological phenotype of several prevalent metabolic and genetic bone diseases. Pyruvate kinase muscle isoenzyme 2 (PKM2) regulates the last step of glycolysis, and its role in BMSCs differentiation is still unknown. In this study, the influence of PKM2 on osteogenesis and adipogenesis was assessed in vitro and in vivo. We found that DASA-58 (the activator of PKM2) reduced the enzymatic activity of ALP, and inhibited the levels of osteogenic marker genes, especially RUNX2, which is a crucial transcription factor for osteogenesis. Besides, we provided evidence that C3k, an inhibitor of PKM2, caused increase in mitochondrial membrane potential and maintained low levels of ROS, and promoted mitochondrial fusion. Furthermore, after treatment with DASA-58, the level of active β-catenin gradually decreased, which also inhibited the transport of active β-catenin into the nucleus, but C3k obviously promoted its nuclear translocation. As for adipogenesis, PKM2 activation increased the expression of adipogenic related genes and decreased active-β-catenin expression, whereas treatment of C3k had the opposite effect. In addition, C3k significantly attenuated ovariectomy-induced trabecular bone loss in vivo. Our findings helped uncover the molecular mechanisms underlying PKM2 regulation of BMSCs differentiation.