外泌体miRNAs介导的成骨-软骨细胞通讯调控骨折愈合的机制研究

The mechanism of crosstalk between osteoblast and chondrocyte during the process of fracture healing remains unclear. Exosome, a nanoscale extracellular vesicle with lipid bi-layers structure, which contains functional materials such as miRNAs and proteins, plays a vital role in cell-to-cell communication. Our previous studies have found that osteoblast and chondrocyte could secrete exosome, and preliminary experiment also showed both of them could affect the other’s biological function via this secretory vesicle. Moreover, it had been proved by a number of studies that exosomal miRNAs act as an important signal molecule in cell communication. Based on above, a hypothesis was put forward: osteoblast and chondrocyte communicate with each other by the means of miRNAs-rich exosome during the fracture healing process. This project will specify the role of exosome and its containing miRNAs in osteoblast-chondrocyte communication by co-culture, miRNAs chips, miRNAs overexpression or silence technology. In addition, a nano-scaffold combination with exosome will be applied in a mandibular fracture model to verify the effect of exsome on fracture healing. This project will deeply clarify the regulatory role of exosome and its containing miRNAs in osteoblast-chondrocyte communication from multiple perspectives, and make further investigation regarding the molecular biology mechanism of fracture healing.

骨折愈合过程中，成骨细胞和软骨细胞之间的交互作用机制尚不清楚。外泌体是一种具有脂质双层膜结构的纳米级小囊泡，其内载有miRNAs及功能性蛋白质等物质，在细胞间的信息传递过程中发挥重要作用。本项目的前期研究发现成骨细胞和软骨细胞均能分泌外泌体，并且通过外泌体影响另一方的生物学功能。研究表明，外泌体主要是通过其内含的miRNAs发挥作用。由此，我们认为骨折愈合过程中，成骨细胞和软骨细胞之间以富含miRNA的外泌体为媒介展开“对话”。本课题拟通过共培养技术、miRNAs芯片、miRNAs过表达或沉默技术，明确外泌体及其来源的miRNAs在成骨-软骨细胞通讯中的作用；并通过构建下颌骨骨折动物模型，利用纳米支架材料复合外泌体，探讨外泌体对骨折愈合的影响。本项目将从多个角度阐明外泌体及其miRNAs在成骨细胞与软骨细胞通讯中的调控机制，进一步完善骨折愈合过程的分子生物学机理。

在骨损伤修复过程的微环境中，骨相关细胞之间的交互作用机制尚不清楚。外泌体是一种具有脂质双层膜结构的纳米级小囊泡，其内载有功能性蛋白质、核酸等物质，在细胞间的信息传递过程中发挥重要作用。本项目研究发现软骨细胞来源的外泌体能够通过基因工程化改造，发挥促进骨形成和血管生成的作用。同时我们发现间充质干细胞来源的外泌体也具有强大的促进骨形成的能力。本课题组通过学科交叉的模式，合作开发了多种新型多功能生物支架材料，应用于骨组织再生。我们利用这些生物支架材料复合外泌体，探讨外泌体对骨损伤修复的影响。本项目的研究为外泌体相关骨再生的分子机制和骨缺损修复治疗提供了一些新的见解和潜在治疗策略。