The role of androgens in osteoblast development and bone metabolism.

雄激素在成骨细胞发育和骨代谢中的作用。

• 批准号: nhmrc : 350346
• 负责人: A/Pr Rachel Davey
• 金额: $ 32.51万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-androgens-osteoblast-bone-metabolism/100422
• 关键词: role; androgens; osteoblast; development; bone

Maintenance of the skeleton involves the processes of bone formation by cells known as osteoblasts and bone breakdown by cells known as osteoclasts. When these processes become unbalanced, bone loss results, which is the basis of osteoporosis. The reduced bone mass found in osteoporosis leads to an increased susceptibility to bone fracture. 1 in 2 women and 1 in 3 men over the age of 60 will suffer a fracture due to osteoporosis. The increasing incidence of osteoporotic fractures has lead to renewed efforts to understand the actions of hormones on bone. Androgens, the male sex hormones, have beneficial effects on skeletal growth and bone maintenance in both males and females by stimulating osteoblasts. It is believed that androgens act by binding to a specific protein known as the androgen receptor (AR), which is only found in androgen-responsive cells. Although it is well documented in human and animal models that androgens stimulate osteoblasts to increase the formation of bone, the way in which they act on osteoblasts remains poorly understood. The aim of this project is to investigate the effects of androgens at different stages of the developing osteoblast. This will be achieved by making transgenic mice in which the androgen receptor has been inactivated only in osteoblasts at specific stages of their development. We hypothesise that the inactivation of the androgen receptor will have dramatic effects on the development and function of osteoblasts. This project will help clarify the role androgens play in bone formation and will give fundamental insights into the basic biology of bone in both normal and disease processes. As androgens are one of the few agents that act to increase bone formation, understanding the way in which they act is important for the treatment of osteoporosis in males and females. We believe that this research is of great importance as osteoporosis becomes more prevalent in our aging population.

骨骼的维持包括成骨细胞的骨形成过程和破骨细胞的骨分解过程。当这些过程变得不平衡时，就会导致骨质流失，这是骨质疏松症的基础。骨质疏松症中发现的骨量减少会导致骨折的易感性增加。在60岁以上的妇女中，每2人中就有1人，每3人中就有1人会因骨质疏松症而骨折。随着骨质疏松性骨折发病率的增加，人们开始重新努力了解激素对骨骼的作用。雄激素是一种男性性激素，通过刺激成骨细胞对男性和女性的骨骼生长和骨骼维持产生有益影响。据信，雄激素通过与称为雄激素受体（AR）的特定蛋白质结合而起作用，该蛋白质仅在雄激素应答细胞中发现。虽然在人类和动物模型中有充分的证据表明雄激素刺激成骨细胞以增加骨的形成，但它们对成骨细胞的作用方式仍然知之甚少。本项目的目的是研究雄激素在成骨细胞发育的不同阶段的作用。这将通过制造转基因小鼠来实现，在转基因小鼠中，雄激素受体仅在成骨细胞发育的特定阶段被灭活。我们假设雄激素受体的失活将对成骨细胞的发育和功能产生显著影响。该项目将有助于阐明雄激素在骨形成中的作用，并将对正常和疾病过程中骨的基本生物学提供基本见解。由于雄激素是少数几种增加骨形成的药物之一，因此了解它们的作用方式对于男性和女性骨质疏松症的治疗非常重要。我们认为，这项研究是非常重要的，因为骨质疏松症在我们的老龄化人口中变得更加普遍。