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。 公共卫生相关性：破骨细胞是由巨噬细胞融合形成的多核细胞，并负责与骨质疏松症和类风湿性关节炎相关的骨丢失。外来体是由细胞（包括巨噬细胞）释放的病毒样膜结合囊泡，其存在于细胞外液（包括血液和乳汁）中。我们建议从形态学和生物化学上分离和表征通过融合形成破骨细胞的人单核细胞释放的外泌体，以提高我们对破骨细胞生成的理解，并可能将其用作评估破骨细胞介导的骨丢失的生物标志物。

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. PUBLIC HEALTH RELEVANCE: Osteoclasts are multinucleate cells that form by fusion of macrophages and are responsible for bone loss associated with osteoporosis and rheumatoid arthritis. Exosomes are virus-like membrane bound vesicles released by cells, including macrophages, which are present in extracellular fluids, including blood and milk. We propose to isolate and characterize morphologically and biochemically exosomes released by fusing human monocytes, which form osteoclasts, to improve our understanding of osteoclastogenesis and to potentially use them as biomarkers to assess osteoclast-mediated bone loss.