Role of thyroid hormone receptors in osteoclast differentiation and function

甲状腺激素受体在破骨细胞分化和功能中的作用

• 批准号: G0800261/1
• 负责人: John Bassett
• 金额: $ 62.2万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800261%2F1
• 关键词: Role; thyroid; hormone; receptors; osteoclast

Osteoporosis is a major health priority affecting half of women and one in five men over 50 and costing the NHS #1.7 billion a year. Thyrotoxicosis is an established cause of osteoporotic fracture but the underlying mechanism of bone loss has not been determined. Our recent studies, however, indicate that thyroid hormone receptor alpha (TRalpha) has a critical role in skeletal development, acquisition and maintenance of adult bone and thyrotoxic bone loss. Moreover, our studies suggest that TRalpha has an important role in regulating the activity of bone resorbing osteoclasts. Although the mechanism is unknown these studies identify TRalpha as a potential new drug target for the treatment and prevention of osteoporosis. Importantly, the therapeutic potential of TR-isofom specific compounds has already been demonstrated in patients with for high cholesterol. In the proposed studies Dr Bassett and Professor Williams at the MRC Clinical Sciences Centre, Imperial College London, will characterise the actions of T3 in osteoclasts and their subsequent effects on bone structure and strength. These studies are critical and timely as it is essential that the molecular mechanism of thyrotoxic bone loss is defined, before new drugs, acting on TRalpha are developed for the treatment of osteoporosis.

骨质疏松症是一个主要的健康优先事项，影响着50岁以上的一半女性和五分之一的男性，每年要花费NHS 17亿英镑。甲状腺机能亢进症是骨质疏松性骨折的既定原因，但骨丢失的潜在机制尚未确定。然而，我们最近的研究表明，甲状腺激素受体α(TRpha)在骨骼发育、成人骨的获得和维持以及甲状腺毒性骨丢失中起着关键作用。此外，我们的研究表明，TRpha在调节骨吸收破骨细胞的活性方面具有重要作用。尽管其作用机制尚不清楚，但这些研究确定TRpha是治疗和预防骨质疏松症的潜在新药靶点。重要的是，tr-异构酶特异性化合物的治疗潜力已经在高胆固醇患者中得到证明。在拟议的研究中，伦敦帝国理工学院MRC临床科学中心的巴西特博士和威廉姆斯教授将描述T3在破骨细胞中的作用以及它们随后对骨骼结构和强度的影响。这些研究是关键和及时的，因为在开发作用于TRpha的治疗骨质疏松症的新药之前，确定甲状腺毒性骨丢失的分子机制是至关重要的。