The physiological role of calcitonin and its receptor in bone cell metabolism.

降钙素及其受体在骨细胞代谢中的生理作用。

• 批准号: nhmrc : 454484
• 负责人: A/Pr Rachel Davey
• 金额: $ 33.1万
• 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: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/physiological-role-calcitonin-cell-metabolism/97631
• 关键词: physiological; role; calcitonin; its; receptor

Throughout adult life, bone tissue is continuously remodelled. The two main processes involved in bone remodelling, are bone formation and bone breakdown. Bone formation is controlled by cells known as osteoblasts and bone breakdown is controlled by cells known as osteoclasts. Under normal circumstances these two processes are tightly coupled. Excessive breakdown of bone, causes these two processes to become unbalanced and results in bone loss. This is the basis of many bone diseases such as osteoporosis, a condition in which the bones become fragile and therefore more susceptible to fracture. 1 in 2 women and 1 in 3 men aged 70 years and older suffer from osteoporosis in Australia. Despite this, the mechanisms which control osteoclast breakdown of bone are not well understood. Our laboratory is interested in how hormones affect osteoclast action. We plan to examine the role of the hormone calcitonin, an important inhibitor of osteoclastic bone breakdown. This will be achieved by studying transgenic mice in which the receptor, or target, for calcitonin is specifically removed from osteoclasts. This will allow us to precisely determine the role of calcitonin in osteoclast function. Data generated by our research group indicates that calcitonin is also involved in controlling bone formation, however, the way in which calcitonin acts on osteoblasts remains poorly understood. Therefore, studying our transgenic mice will also help clarify the role calcitonin plays in bone formation. Current treatment for osteoporosis involves the administration of drugs which inhibit bone breakdown. This project will increase our understanding of how calcitonin acts to regulate bone breakdown and bone formation and may assist in the design of new therapies for osteoporosis. We believe that this research is of great importance as osteoporosis is becoming more prevalent as the population ages.

在整个成年期，骨组织不断被重塑。骨重塑的两个主要过程是骨形成和骨分解。骨形成由称为成骨细胞的细胞控制，骨分解由称为破骨细胞的细胞控制。在正常情况下，这两个过程是紧密耦合的。骨质的过度破坏，导致这两个过程变得不平衡，导致骨质流失。这是许多骨骼疾病的基础，如骨质疏松症，在这种情况下，骨骼变得脆弱，因此更容易骨折。在澳大利亚，70岁及以上的老年人中，每2名女性中就有1名患有骨质疏松症，每3名男性中就有1名患有骨质疏松症。尽管如此，控制破骨细胞破坏骨骼的机制尚不清楚。我们实验室对激素如何影响破骨细胞的作用很感兴趣。我们计划研究激素降钙素的作用，降钙素是一种重要的破骨细胞骨破坏抑制剂。这将通过研究从破骨细胞中特异性去除降钙素受体或靶标的转基因小鼠来实现。这将使我们能够精确地确定降钙素在破骨细胞功能中的作用。我们的研究小组产生的数据表明，降钙素也参与控制骨形成，然而，降钙素对成骨细胞的作用方式仍然知之甚少。因此，研究我们的转基因小鼠也将有助于阐明降钙素在骨形成中的作用。目前对骨质疏松症的治疗包括使用抑制骨质破坏的药物。这个项目将增加我们对降钙素如何调节骨分解和骨形成的理解，并可能有助于设计治疗骨质疏松症的新疗法。我们认为，随着人口老龄化，骨质疏松症变得越来越普遍，这项研究具有重要意义。