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The role of signal of low-density lipoprotein-related protein receptor in bone after intermittent skeletal loading

间歇性骨骼负荷后骨中低密度脂蛋白相关蛋白受体信号的作用

基本信息

批准号：
16390446
负责人：
NAKAMURA Toshitaka
金额：
$ 9.04万
依托单位：
University of Occupational and Environmental Health, Japan
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

项目摘要

The results during the 4-year research period were summarized as follows.1) The trabecular bone volume, bone formation rate, and osteoblast surface were reduced in the mice fed with high-fat diet compared with the mice fed with standard diet. The serum levels of low-density lipoprotein (LDL) and oxidized LDL were elevated in the mice fed with high-fat diet compared with the mice fed with standard diet. LDL and oxidized LDL induced apoptosis of osteoblasts in the cell culture study.2) Fat tissue stained by oil-red O was reduced and bone tissue was increased in the histological sections 7 days after climbing exercise. In the bone marrow cells of climbing mice (intermittent skeletal loading model mice), LRP5 (LDL receptor-related protein 5) and wnt/β-catenin mRNA expressions were enhanced through PTH/PTHrP receptor signal 4 days after climbing exercise. C/EBPβ and C/EBP8 decreased 4 days, and aP2 and PEPCK decreased 7 days after climbing exercise. We resulted that climbing exercise inhibits adipogenic differentiation and promotes osteogenic differentiation by highly expressed LRP-5 and wnt/β-catenin mRNA through PTH/PTHrP receptor.3) We clarified the association of radiological findings of spinal osteoarthritis with genetic type of Wnt-1-induced secreted protein 1 (WISP1) or with single-nucleotide polymorphism of LRP5 in postmenopausal Japanese women.

结果表明：（1）高脂饮食组小鼠骨小梁体积、骨形成率和成骨细胞表面积均低于标准饮食组。高脂饲料喂养小鼠血清低密度脂蛋白（LDL）和氧化型LDL水平较标准饲料喂养小鼠升高。在细胞培养研究中，LDL和氧化LDL均能诱导成骨细胞凋亡。2）攀爬运动后7 d，组织切片中油红O染色的脂肪组织减少，骨组织增加。登山运动后4d，通过PTH/PTHrP受体信号，登山小鼠（间歇性骨骼负荷模型小鼠）骨髓细胞LRP 5（LDL receptor related protein 5）和wnt/β-catenin mRNA表达增强。C/EBPβ和C/EBP 8在攀爬运动后4天下降，aP 2和PEPCK在攀爬运动后7天下降。我们的结果是，攀岩运动通过PTH/PTHrP受体高表达LRP-5和wnt/β-catenin mRNA来抑制成脂分化并促进成骨分化。3）我们阐明了脊柱骨关节炎的放射学发现与Wnt-1诱导的分泌蛋白1（WISP 1）的遗传类型或绝经后日本女性LRP 5的单核苷酸多态性的相关性。