DHODH缺失对线粒体功能和成骨细胞分化成熟影响的研究  

Study on effects of DHODH deficiency on mitochondrial function and differentiation and maturation in osteoblast cells

作　　者：方静娴[1] 钱虹[1] 刘河娣[1] 唐翔[2] 

机构地区：[1]南方医科大学口腔医院/广东省口腔医院儿童牙科,广州510280 [2]广州医科大学附属第二医院妇科,广州510260

出　　处：《重庆医学》2017年第10期1312-1314,共3页Chongqing medicine

基　　金：广东省自然科学基金资助项目(2015A030310105);广州市卫生局医药卫生科技项目(20161A011070);广州医科大学博士科研启动项目(2014C34)

摘　　要：目的探讨二氧乳清酸脱氢酶(DHODH)缺失对线粒体功能和成骨细胞分化成熟的影响。方法通过特异性小干扰RNA(siRNA)技术抑制小鼠胚胎成骨细胞前体细胞MC3T3-E1细胞中DHODH表达后,观察细胞增殖、三磷酸腺苷(ATP)产量及骨发育相关基因表达水平。结果特异性siRNAs降低DHODH表达后,细胞增殖受抑制、细胞周期停滞于G_1/S期。全细胞ATP产量,特别是线粒体来源的ATP减少。与对照组相比,DHODH抑制组中Runt相关转录因子2(Runx2)及骨钙素(Ocn)的mRNAs表达量降低。结论抑制DHODH蛋白影响成骨细胞的分化与成熟。成骨细胞中线粒体功能异常可能是导致米勒综合征骨发育异常的原因之一。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,es- pecially 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.

关 键 词：二氢乳清酸脱氢酶 线粒体 成骨细胞 米勒综合征 

分 类 号：R745.43[医药卫生—神经病学与精神病学]