Osteoclast Exosomes

描述（由申请人提供）：巨噬细胞融合是形成多核破骨细胞的关键步骤，多核破骨细胞是骨质疏松症、类风湿性关节炎和牙周病相关骨质流失的原因。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。融合是一个受调控的发育过程，使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，其结构在肿瘤和液体中已被很好地表征，但其功能仍知之甚少。由于所有细胞都会释放外泌体，我们假设巨噬细胞融合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，我们也假设通过融合人类破骨细胞释放的外泌体表达特定的蛋白质和rna，可被用作评估导致骨质流失的破骨细胞形成的生物标志物。因此，我们建议使用显微镜、蛋白质组学、RNA微阵列分析和microRNA谱分析对融合人类单核细胞释放的外泌体进行形态学和生化表征。

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.