Relevance of osteal macrophages in bone remodeling

骨基质通过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增加可导致骨质疏松症，骨质疏松症是老年人最常见的疾病之一。我们之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Il33，可能参与骨重塑的调节。为了分析这种可能性，我们将在体外研究这两种细胞因子对骨细胞的影响，我们将研究Ccl5、Il33或其受体表达改变的基因工程小鼠模型。此外，我们将分析骨微环境中的哪些细胞类型是细胞因子的来源，并进行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一些分子机制。综上所述，该项目不仅为新兴的骨免疫学领域增加了重要的信息，而且还为骨质疏松症、转移性骨病或骨关节炎等骨质流失疾病的治疗发现了新的靶蛋白。

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.