Study on effects of DHODH deficiency on mitochondrial function and differentiation and maturation in osteoblast cells / 重庆医学

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.