The role of androgens in osteoblast development and bone metabolism.

骨骼的维持包括成骨细胞形成骨骼和破骨细胞分解骨骼的过程。当这些过程变得不平衡，骨质流失的结果，这是骨质疏松症的基础。骨质疏松症患者骨量减少导致骨折易感性增加。60岁以上的女性中有1 / 2，男性中有1 / 3会因骨质疏松而骨折。骨质疏松性骨折的发病率不断增加，这促使人们重新努力了解激素对骨骼的作用。雄激素，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护都有有益的影响。人们认为雄激素是通过与一种叫做雄激素受体（AR）的特定蛋白质结合而起作用的，这种蛋白质只存在于雄激素反应细胞中。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。本项目旨在探讨雄激素在成骨细胞发育不同阶段的作用。这将通过制造转基因小鼠来实现，其中雄激素受体仅在成骨细胞发育的特定阶段失活。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重大影响。该项目将有助于阐明雄激素在骨形成中的作用，并将为正常和疾病过程中骨骼的基本生物学提供基本见解。由于雄激素是为数不多的促进骨形成的药物之一，了解它们的作用方式对治疗男性和女性骨质疏松症很重要。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越来越普遍。

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.