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.
ABSTRACT
@#ObjectiveTo study the relationship between vitamin D receptor (VDR) gene polymorphism and calcitonin receptor (CTR) gene polymorphism, and bone mineral density (BMD) of the Han nationality woman in Hebei, explore the pathogenesis of osteoporosis (OP) at the gene level.MethodsPolymorphisms of VDR gene and CTR gene were analyzed by restriction fragment length polymorphisms (RFLPs) in 60 Han nationality women in Hebei.ResultsBb genetype of VDR had lower BMD values at all sites which were measured compared with bb genetype (P<0.05); CC genetype of CTR had tendency for lower BMD values at the L1～L4 compared with CT genetype (0.05<P<0.1); BMD value of CCBb genetype was the lowest.ConclusionBb genetype of VDR has a relationship with lower BMD. CCBb genetype can act as a heredity mark of OP in Chinese Han nationality woman.