Study on effects of DHODH deficiency on mitochondrial function and differentiation and maturation in osteoblast cells
10.3969/j.issn.1671-8348.2017.10.005
- VernacularTitle:DHODH缺失对线粒体功能和成骨细胞分化成熟影响的研究
- Author:
Jingxian FANG
;
Hong QIAN
;
Hedi LIU
;
Xiang TANG
- Keywords:
dihydroorotate dehydrogenase;
mitochondria;
osteoblast cells;
Miller syndrome
- From:
Chongqing Medicine
2017;46(10):1312-1314
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the changes of the skeletal development related cells after dihydroorotate dehydrogenase (DHODH) deficiency.Methods The DHODH expression in MC3T3-E1 cells derived from mouse calvaria osteoblast precursor cells was inhibited by specific small interfering RNAs (siRNAs),and cell proliferation,ATP production and expression levels of bone-related genes were investigated in these cells.Results After reducing the DHODH expression by using specific siRNAs,cell proliferation was inhibited and cell cycle was arrested at G1/S stage.In addition,the ATP production was reduced in whole cells,especially in mitochondria.Furthermore,the expression levels of Runt-related transcription factor 2 (Runx2) and osteocalcin (Ocn) mRNAs in the DHODH inhibition group were decreased compared with the control group.Conclusion Inhibiting DHODH protein affects the differentiation and maturation of osteoblasts.The mitochondrial dysfunction in osteoblasts may be one of causes leading to the abnormal bone formation in Miller syndrome.