Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency.
10.1038/s41368-022-00204-1
- Author:
Zheng LI
1
;
Muxin YUE
1
;
Boon Chin HENG
2
,
3
,
4
,
5
;
Yunsong LIU
1
;
Ping ZHANG
6
;
Yongsheng ZHOU
7
Author Information
1. Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
2. National Center of Stomatology &
3. National Clinical Research Center for Oral Diseases &
4. National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &
5. Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, China.
6. Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China. zhangping332@hsc.pku.edu.cn.
7. Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China. kqzhouysh@hsc.pku.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Mice;
Animals;
Metformin/pharmacology*;
Phosphoenolpyruvate Carboxykinase (ATP)/metabolism*;
Gluconeogenesis/genetics*;
Mice, Knockout
- From:
International Journal of Oral Science
2022;14(1):54-54
- CountryChina
- Language:English
-
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.
