Osteoclast Exosomes

描述（由申请方提供）：巨噬细胞的融合是多核破骨细胞形成的关键步骤，多核破骨细胞导致骨质疏松症、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，形成多核巨细胞。融合是一种受调节的发育事件，允许巨噬细胞成为多核细胞并获得新的功能。外泌体是由细胞（包括巨噬细胞）释放的小病毒样颗粒，其结构在肿瘤和体液中已得到很好的表征，但其功能仍知之甚少。由于所有细胞都释放外泌体，我们假设融合巨噬细胞释放的外泌体可能参与融合过程。此外，由于外泌体存在于体液中，并被用作检测癌症等疾病的生物标志物，我们还假设通过融合人破骨细胞释放的外泌体表达特定的蛋白质和RNA，这些蛋白质和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分析来表征融合人单核细胞释放的外泌体的形态学和生物化学特征。

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.