Relevance of osteal macrophages in bone remodeling

骨巨噬细胞在骨重塑中的相关性

• 批准号: 168927610
• 负责人: Professor Dr. Michael Amling
• 金额: --
• 依托单位: Institut für Osteologie und Biomechanik (IOBM)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/168927610?language=en
• 关键词: Relevance; osteal; macrophages; bone; remodeling

The bone matrix is constantly remodelled through the activities of bone-forming osteoblasts and bone-resorbing osteoclasts, and a relative increase of bone resorption over bone formation can result in osteoporosis, one of the most prevalent diseases of the aged population. Our previous analysis of two different osteoporotic mouse models has suggested that specific cytokines, such as Ccl5 and Il33, may be involved in the regulation of bone remodelling. To analyze this possibiliy we will study the effects of both cytokines on bone cells in vitro, and we will study genetically engineered mouse models with altered expression of either Ccl5, Il33 or their receptors. In addition, we will analyze, which cell types within the bone microenvironment are the source of both cytokines and perform cocultureexperiments of bone-forming osteoblasts and osteal macrophages to uncover some of the molecular mechanisms underlying the interactions between bone and immune cells. Taken together, this project should not only add significant information to the emerging field of osteoimmunology, but also identify novel target proteins for the treatment of bone loss disorders, such as osteoporosis, metastatic bone disease or osteoarthritis.

骨基质通过骨形成成骨细胞和骨吸收破骨细胞的活动不断重塑，骨吸收相对于骨形成的相对增加可导致骨质疏松症，这是老年人群中最普遍的疾病之一。我们先前对两种不同的骨质疏松小鼠模型的分析表明，特定的细胞因子，如Ccl5和IL 33，可能参与骨重建的调节。为了分析这种可能性，我们将研究这两种细胞因子对体外骨细胞的影响，并且我们将研究Ccl 5、Il 33或其受体表达改变的基因工程小鼠模型。此外，我们还将分析骨微环境中哪些细胞类型是细胞因子的来源，并进行骨形成成骨细胞和骨巨噬细胞的共培养实验，以揭示骨和免疫细胞之间相互作用的分子机制。总之，该项目不仅应该为骨免疫学的新兴领域增加重要信息，而且还可以确定用于治疗骨质疏松症，转移性骨病或骨关节炎等骨丢失疾病的新型靶蛋白。