淀粉样蛋白β异常表达对骨代谢的影响  

Abnormally expressed beta-amyloid affects bone metabolism

作　　者：李芳瑜 夏文芳[1] 崔舜[1] Li Fangyu;Xia Wenfang;Cui Shun(Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430000,Hubei Province,China)

机构地区：[1]华中科技大学同济医学院附属协和医院,湖北省武汉市430000

出　　处：《中国组织工程研究》2022年第20期3152-3157,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81671560),项目负责人:崔舜。

摘　　要：背景:淀粉样蛋白β在人体组织中广泛存在,它的异常表达与阿尔茨海默症、骨质疏松等多种慢性炎症性疾病密切相关。研究表明淀粉样蛋白β在人椎骨和股骨中沉积并引起骨质破坏,但关于淀粉样蛋白β低表达对骨代谢的影响尚不清楚。目的:探讨淀粉样蛋白过表达及低表达对小鼠骨代谢的影响。方法:纳入12月龄淀粉样蛋白β过表达的APPswe^(+/+)转基因小鼠(APPswe^(+/+)组)、淀粉样蛋白β低表达的β-分泌酶1基因敲除小鼠(BACE-/-组)和野生型小鼠(野生型组)。刚果红染色观察淀粉样蛋白在骨组织中的沉积;免疫组织化学染色检测淀粉样蛋白前体蛋白在骨组织的分布,Micro-CT研究整体骨结构差异性;碱性磷酸酶染色和抗酒石酸酸性磷酸酶染色,分析骨形成及骨吸收的差异性。结果与结论:①与野生型组相比,APPswe^(+/+)组小鼠松质骨和致密骨淀粉样蛋白β沉积增多,BACE-/-组小鼠松质骨和致密骨淀粉样蛋白β沉积减少(P<0.05);②淀粉样蛋白前体蛋白在APPswe^(+/+)组和BACE-/-组小鼠的松质骨表达增多;③与野生型组相比,APPswe^(+/+)组和BACE-/-组小鼠骨小梁的骨量和骨小梁厚度减少,骨小梁变细、稀疏、排列紊乱或断裂;骨形成异常,破骨细胞活性增强(P<0.05);④淀粉样蛋白β过表达或低表达均可引起骨代谢紊乱,导致骨质流失;β-分泌酶1基因敲除导致淀粉样蛋白β异常低表达,影响淀粉样前体蛋白在骨中的表达,导致骨代谢异常。BACKGROUND:Amyloidβexists widely in human tissues,and its abnormal expression is closely related to various chronic inflammatory diseases such as Alzheimer’s disease and osteoporosis.Studies have shown that amyloidβdeposits in human vertebrae and femur and then causes bone destruction.However,the effect of low expression of amyloidβon bone metabolism remains unclear.OBJECTIVE:To investigate the effect of overexpression and low expression of amyloidβon bone metabolism in mice.METHODS:There were three groups:an APPswe^(+/+)group with APPswe^(+/+)transgenic mice aged 12 months with overexpression of amyloidβ,a BACE-/-group withβ-secretase cleaving enzyme-1 gene knockout mice with low expression of amyloidβ,and a wild type group with wild type mice.Amyloidβdeposition in bone tissue was observed by Congo red staining.Immunohistochemical staining was used to detect the distribution of amyloid precursor protein in bone tissue,and micro-computed tomography was used to study the difference of overall bone structure.Alkaline phosphatase staining and tartrate-resistant acid phosphatase staining were used to analyze the differences between bone formation and bone resorption.RESULTS AND CONCLUSION:Compared with the wild type group,amyloidβdeposition of cancellous bone and compact bone was increased in the APPswe^(+/+)group,and decreased in the BACE-/-group(P<0.05).Compared with the wild type group,the expression of amyloid precursor protein in mouse cancellous bone was increased in the APPswe^(+/+)and BACE-/-groups.Compared with the wild type group,the bone mass and thickness of trabecular bone were decreased,and trabecular bone became thinner,sparse,disordered or fractured in the APPswe^(+/+)and BACE-/-groups.There was also abnormal bone formation and enhanced activity of osteoclasts in the APPswe^(+/+)and BACE-/-groups(P<0.05).To conclude,overexpression or low expression of amyloidβcan cause bone metabolism disorder and lead to bone loss.Abnormal lower expression of amyloidβcaused byβ-secretase cleaving enzyme

关 键 词：淀粉样蛋白β 骨代谢 β-分泌酶1 淀粉样前体蛋白 骨质破坏 

分 类 号：R459.9[医药卫生—治疗学] R681[医药卫生—临床医学]