Role of bone-associated macrophages in bone remodelling and bone disease

肌肉骨骼疾病，包括骨质疏松症和骨关节炎，是国家和国际卫生和研究的优先事项。超过300万澳大利亚人患有关节炎和肌肉骨骼疾病，由于人口老龄化，他们的社会和经济影响预计将在未来20年急剧增加。许多肌肉骨骼疾病的早期诊断、预防和治疗目前是不足的。因此，对有效治疗方案的需求很大。该项目拨款申请提出了一条新的科学研究路线，将更好地了解巨噬细胞（一种在正常组织维持和防御感染中起重要作用的细胞类型）在骨重塑和疾病中的作用。骨骼不断被重塑和替换，以维持骨骼强度和矿物质代谢。我们已经证明巨噬细胞群与骨密切相关，并提出这些细胞在调节骨重塑中起重要作用。巨噬细胞与许多具有骨损伤后果的疾病有关，包括骨质疏松症和几种形式的关节炎，巨噬细胞异常功能与疾病相关的骨损伤有关。本项目旨在描述骨相关巨噬细胞的特征，并确定它们影响骨重塑过程中其他细胞功能的能力。我们还将在动物模型中进行研究，以确定这些细胞是否需要用于骨重塑和或损伤。详细描述巨噬细胞在骨生物学中的新作用将有助于开发更好的治疗方法，预防和治疗骨疾病。

Musculoskeletal diseases, including osteoporosis and osteoarthritis, are a national and international health and research priorities. Over 3 million Australians suffer from arthritis and musculoskeletal conditions and their social and economic impact is expected to dramatically increase in the next 20 years as a result of the aging population. Early diagnosis, prevention and treatment of many musculoskeletal diseases are currently inadequate. Consequently, there is a high demand for effective treatment options. This project grant application proposes a novel line of scientific investigation that will provide greater understanding of the contribution of macrophages (a cell type that has important roles in normal tissue maintenance and defense against infection) in bone remodelling and disease. Bone is continuously remodelled and replaced to maintain skeletal strength and mineral metabolism. We have shown that a population of macrophages is intimately associated with bone and propose that these cells play an important part in regulating bone remodelling. Macrophages have been implicated in many diseases that have damaging consequences on bone, including osteoporosis and several forms of arthritis, linking aberrant macrophage function to disease-associated bone damage. This project aims to characterize this population of bone-associated macrophages and determine their ability to influence the function of other cells integrally involved in bone remodelling. We will also undertake studies in animal models to determine whether these cells are required for bone remodelling and-or damage. Detailed description of the novel role of macrophages in bone biology will facilitate the development of superior therapeutics, preventatives and cures for bone diseases.