晚期氧化蛋白产物诱导成骨细胞凋亡的机制研究

项目名称： 晚期氧化蛋白产物诱导成骨细胞凋亡的机制研究

项目编号： No.81472135

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 钟招明

作者单位： 南方医科大学

项目金额： 72万元

中文摘要： 成骨细胞凋亡与骨质疏松症发生发展密切相关。我们的前期研究证实晚期氧化蛋白产物（AOPP）不仅是氧化应激标志物，也是一类内源性致病介质，AOPP蓄积与增龄性骨量丢失呈正相关；AOPP能加速老年大鼠骨量丢失、骨质退化,抑制成骨样细胞增值与成骨分化,上述效应能被NAPDH氧化酶抑制剂阻断。进一步预实验表明AOPP可诱导成骨细胞凋亡，但其具体机制尚不清楚。本项目拟通过体内、体外研究模型，探讨⑴ AOPP对成骨细胞凋亡的作用及其与骨量丢失的相关性；⑵ AOPP诱导成骨细胞凋亡的分子基础，包括受体途径、NAPDH氧化酶及下游的氧化还原敏感信号、细胞凋亡调控分子；⑶阻断AOPP生物学效应对成骨细胞凋亡和骨质疏松的干预作用。本项目将从分子-细胞-动物水平阐明AOPP诱导成骨细胞凋亡的作用及其机制，进一步揭示骨质疏松症发病学的新机制，为开拓骨质疏松症防治的新途径提供理论依据。

中文关键词： 晚期氧化蛋白产物；成骨细胞；凋亡；NAPDH氧化酶；骨质疏松

英文摘要： Osteoblast apoptosis was closely related to the occurrence and development of osteoporosis. Our previous study demonstrated advanced oxidation protein products (AOPP) was a marker of oxidative stress, and also a kind of endogenous pathological mediator. Accumulation of AOPP was positively related to the age-related bone loss. AOPP challenge could accelerate bone loss and bone degradation in aged rats, and inhibit the cell proliferation and osteogenic differentiation in osteoblast-like cells. These effects were reversed by NAPDH oxidase inhibitors.Our preliminary experiment showed that AOPP can induce the apoptosis of osteoblasts, but its mechanism is still unclear. By in vivo and in vitro studies, the project is planned to investigate: (1) the pathological role of AOPP on the osteoblast apoptosis and its relationship to bone loss,(2) the molecular basis of osteoblast apoptosis induced by AOPP,including its receptors, NAPDH oxidase and its downstream redox-sensitive signals, and regulatory molecules of cell apoptosis,(3)the effect of blocking the cell signal pathways on the AOPP-induced osteoblast apoptosis, and their intervention effect of osteoporosis. This project would elucidate the role and mechanism of AOPP in osteoblast apoptosis at the molecular, cellular, and animal levels.It would further reveal the new pathogenetic mechanism underlying osteoporosis, and provide a theoretical basis for the development of new prevention and treatment strategies in osteoporosis.

英文关键词： Advanced oxidation protein products;Osteoblast;Apoptosis;NADPH oxidase;Osteoporosis