共转录因子CITED1在小鼠骨代谢中的调控作用  

Regulation of co-transcription factor CITED1 in mouse bone metabolism

作　　者：邱奕雁[1,2] 郑羽晨 郭伟壮 周文钰[1] 颜滨[1] 杨欣建[1] QIU Yi-yan;ZHENG Yu-cheng;GUO Wei-zhuang;ZHOU Wen-yu;YAN Bin;YANG Xin-jian(Department of Orthopedics,the Second People's Hospital of Shenzhen,Shenzhen 518000;Department of Orthopedics,the Third Affiliated Hospital of Southem Medical University,Guangzhou 510630,China)

机构地区：[1]深圳市第二人民医院骨科,广东深圳518000 [2]南方医科大学第三附属医院骨科,广东广州510630

出　　处：《基础医学与临床》2020年第3期294-298,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81802237);深圳科创委基金(JCYJ20160425104432398)

摘　　要：目的在体研究CITED1在骨代谢即成骨/破骨平衡中的调节作用,为骨质疏松的治疗提供相应的理论基础。方法利用野生型小鼠(WT小鼠)和构建的CITED1基因敲除小鼠(KO小鼠),显微电子计算机断层扫描(CT)定量测量WT小鼠和KO小鼠股骨长度、骨量和骨皮质以及骨松质厚度等骨骼表型。用ELISA检测骨代谢的血液学相关指标。用RT-qPCR检测骨标志基因的表达,从分子水平探究骨代谢改变的原因。结果 KO小鼠颅骨成骨细胞中CITED1表达极少,表明敲除成功。KO小鼠股骨长度、骨量和骨皮质以及骨松质厚度显著高于WT小鼠。KO小鼠外周血血清中I型原胶原肽(P1NP)、骨钙素(OC)和骨碱性磷酸酶(BALP)浓度均显著高于WT小鼠,而抗酒石酸酸性磷酸酶(TRAP)的浓度显著低于WT小鼠。RT-qPCR结果显示,KO小鼠颅骨成骨细胞中OC和BALP基因表达较WT小鼠显著增加(P<0. 001);同时,KO小鼠颅骨成骨细胞中抗酒石酸酸性磷酸酶(TRAP)的表达较WT小鼠显著降低(P<0. 05)。结论小鼠CITED1敲除后可以通过上调OC和BALP基因表达,下调TRAP基因的表达,促进骨形成,抑制骨吸收。Objective To study the regulation of CITED1 in the mice bone metabolism,including osteogenesis/osteoclast balance in vivo to provide a theoretical basis for the treatment of osteoporosis. Methods Bone phenotypes such as femur length,bone mass,bone cortex and bone cancellous thickness of KO mice were measured by micro CT. Hematological related parameters of bone metabolism were determined by ELISA. RT-qPCR was used to detect the expression of bone marker genes to explore the causes of bone metabolism changes after CITED1 gene knockout.Results The expression of CITED1 was low in KO mice,indicating a successful CITED1 knockout. Femoral length,bone mass,bone cortex and bone cancellous thickness were significantly higher in KO mice than those in WT mice. The concentration of type Ⅰ procollagen peptide( P1NP),osteocalcin( OC) and bone alkaline phosphatase( BALP) in serum of KO mice was significantly higher than those of WT mice,while the concentration of tartaric acid phosphatase( TRAP) was significantly lower. The expression of OC and BALP in KO mice was significantly higher than that in WT mice( P<0. 001). At the same time the expression of TRAP in KO mice was significantly lower( P < 0. 05). Conclusions CITED1 knockout can up-regulate the expression of OC and BALP,and down-regulate the expression of TRAP for promoting bone formation and inhibiting bone resorption.

关 键 词：共转录因子CITED1 骨质疏松症 甲状旁腺激素 骨代谢 

分 类 号：R589.5[医药卫生—内分泌]