Osteoclast Exosomes

描述(申请人提供)：巨噬细胞的融合是形成多核破骨细胞的关键步骤，多核破骨细胞负责与骨质疏松、类风湿性关节炎和牙周病相关的骨丢失。巨噬细胞也在慢性炎症反应和肿瘤中融合，在那里它们形成多核巨细胞。融合是一种受调控的发育事件，允许巨噬细胞成为多核细胞并获得新的功能。外切体是由包括巨噬细胞在内的细胞释放的类似病毒的小颗粒，其结构在肿瘤和液体中得到了很好的描述，但其功能仍鲜为人知。由于所有细胞都会释放外切体，我们推测巨噬细胞融合后释放的外切体可能参与了融合过程。此外，由于外切体存在于体液中，并被用作检测癌症等疾病的生物标志物，我们还假设，融合人破骨细胞释放的外切体表达特定的蛋白质和RNA，可用作评估破骨细胞形成导致骨丢失的生物标志物。因此，我们建议使用显微镜、蛋白质组学、RNA微阵列分析和microRNA图谱对融合的人单核细胞释放的外切体进行形态和生化特征的表征。

DESCRIPTION (provided by applicant): Fusion of macrophages is a critical step in the formation of multinucleate osteoclasts, which are responsible for bone loss associated with osteoporosis, rheumatoid arthritis and periodontal disease. Macrophages also fuse in chronic inflammatory reactions and in tumors where they form multinucleate giant cells. Fusion is a regulated developmental event that allows macrophages to become multinucleate and acquire a new function. Exosomes are small virus-like particles released by cells, including macrophages, whose structure has been well characterized in tumors and fluids, but whose functions remain poorly understood. Since all cells release exosomes, we hypothesize that exosomes released by fusing macrophages may participate in the fusion process. In addition, since exosomes are present in body fluids and are used as biomarkers to detect diseases such as cancer, we also hypothesize that exosomes released by fusing human osteoclasts express specific proteins and RNAs that can be used as biomarkers to assess osteoclast formation leading to bone loss. We therefore propose to characterize morphologically and biochemically the exosomes released by fusing human monocytes using microscopy, proteomics, RNA microarray analysis and microRNA profiling.