Abstract

As an important enzyme for gluconeogenesis, mitochondrial phosphoenolpyruvate carboxykinase (PCK2) has further complex functions beyond regulation of glucose metabolism. Here, we report that conditional knockout of Pck2 in osteoblasts results in a pathological phenotype manifested as craniofacial malformation, long bone loss, and marrow adipocyte accumulation. Ablation of Pck2 alters the metabolic pathways of developing bone, particularly fatty acid metabolism. However, metformin treatment can mitigate skeletal dysplasia of embryonic and postnatal heterozygous knockout mice, at least partly via the AMPK signaling pathway. Collectively, these data illustrate that PCK2 is pivotal for bone development and metabolic homeostasis, and suggest that regulation of metformin-mediated signaling could provide a novel and practical strategy for treating metabolic skeletal dysfunction.

Details

Title
Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency
Author
Li, Zheng 1 ; Yue, Muxin 1 ; Heng, Boon Chin 2 ; Liu, Yunsong 1 ; Zhang, Ping 1 ; Zhou, Yongsheng 1   VIAFID ORCID Logo 

1  Peking University School and Hospital of Stomatology, Department of Prosthodontics, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319); 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, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319) 
2  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, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319); Peking University School and Hospital of Stomatology, The Central Laboratory, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319) 
Publication year
2022
Publication date
2022
Publisher
Springer Nature B.V.
ISSN
16742818
e-ISSN
20493169
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41368-022-00204-1
ProQuest document ID
2736072335
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.