中文摘要：

目的检测模拟失重状态时牙本质基质蛋白1（dentin matrix protein 1,DMP1）和成骨抑制蛋白（sclerostin,SOST）在小鼠胫骨的表达,以及正常和DMP1基因缺失下SOST的表达,初步探讨DMP1在模拟失重下骨质丧失形成过程中的可能作用及机制。方法 1 1个月龄B6野生型小鼠随机分为悬尾组、对照组（n=5）。悬尾组悬吊1个月后与对照组胫骨石蜡切片进行HE及DMP1和SOST免疫组化染色,实时定量PCR检测Dmp1基因水平的表达。22个月龄B6Dmp1基因敲除鼠制备胫骨石蜡切片,进行SOST免疫组化染色。结果 HE染色显示悬尾组松质骨小梁较对照组稀疏,皮质骨变薄。免疫组化实验显示悬尾鼠DMP1和SOST在骨细胞细胞质和基质中的表达较对照组增高。高倍镜下DMP1和SOST阳性细胞数悬尾组显著高于对照组（P〈0.05,P〈0.01）。Dmp1实时定量PCR结果与免疫组化结果一致,悬尾组表达量为对照组的（2.8±0.4）倍,显著高于对照组（P〈0.01）。SOST在Dmp1基因敲除鼠骨细胞中的表达也较正常增强。结论 DMP1在模拟失重小鼠胫骨中表达增强,提示无力学刺激这一特殊的机械信号可传递至骨细胞,导致其分泌DMP1的改变。SOST在骨形成中具有抑制作用,它在Dmp1基因敲除鼠及悬尾鼠胫骨中表达的增强提示SOST表达上调,导致骨形成减少可能是Dmp1基因敲除鼠和悬尾鼠骨质丧失的一个共同的重要因素。

英文摘要：

Objective To detect the expression of dentin matrix protein 1（ DMP1） and bone formation antagonist sclerostin（ SOST） in the tibia of unloaded mice,and the expression of SOST in wild type mice and DMP1 knockout mice in order to investigate the possible function and mechanism of DMP1 in bone loss process during unloading. Methods Five 1-month-old wild type B6 mice was suspended by tail for 1month. Another 5 mice served as control. HE staining was used to observe the morphological changes of the tibia,immunohistochemical assay were used to detect the expression of DMP1 and SOST in the tibia,and realtime PCR was employed to test the mRNA expression of Dmp1. In addition,SOST expression was also detected in 2-month-old Dmp1 knockout（ KO） mice. Results Pathological observation showed more sparse trabeculae and thinner cortical bone in the unloaded mice than the control. Both immunohistochemical study and real-time PCR showed that expression of DMP1 and SOST were increased in unloaded tibia compared to the control（ P 〈0. 05,P 〈 0. 01）. In addition,SOST expression was also increased in Dmp1 KO mice. Conclusion The expression of DMP1 at both protein and mRNA levels is increased in the osteocytes of unloaded mice,indicating that osteocytes secret more DMP1 after accepting unloading signals. SOST plays inhibitory role in bone formation. The increased expression in Dmp-1 KO mice and unloading mice suggests that bone loss in unloading mice and Dmp1 KO mice may share the same mechanisms through SOST pathway.