Crosstalk between thyroid hormone and Wnt signalling in osteoblasts

成骨细胞中甲状腺激素和 Wnt 信号传导之间的串扰

• 批准号: G0800359/1
• 负责人: Moira Cheung
• 金额: $ 36.9万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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=G0800359%2F1
• 关键词: Crosstalk; between; thyroid; hormone; Wnt

Thyroid hormone (T3) excess causes bone loss, although the underlying mechanisms are unknown. A key cell signalling route in bone is the ‘Wnt‘ pathway. Suppression of Wnt results in high bone turnover leading to bone fragility and osteoporosis, a situation that also occurs in response to T3-excess. Conversely, increased Wnt signalling causes increased bone mass, resembling effects of T3-deficiency on the skeleton. Interactions between T3 and Wnt are well known in intestine, pituitary and kidney but have never been studied in bone. Preliminary studies have shown that Wnt signalling is decreased in bone forming cells (osteoblasts) in response to T3. Dr. Moira Cheung and Professor Graham Williams of the MRC Clinical Sciences Centre, Imperial College London, will study how thyroid hormones inhibit Wnt signalling to regulate osteoblast activity.They will determine:o Which components of the Wnt pathway are regulated by T3o Interactions between T3 and the Wnt pathway in osteoblastso Whether T3 receptors interact with important components of the Wnt pathwayUnderstanding the mechanisms by which T3 acts on bone is important because it may lead to new treatments for osteoporosis, a condition that causes over 230,000 fractures each year costing the NHS over £1.7 billion.

甲状腺激素 (T3) 过量会导致骨质流失，但其潜在机制尚不清楚。骨骼中的一个关键细胞信号传导途径是“Wnt”途径。 Wnt 的抑制会导致高骨转换，从而导致骨脆性和骨质疏松症，这种情况也会因 T3 过量而发生。相反，Wnt 信号传导增加会导致骨量增加，类似于 T3 缺乏对骨骼的影响。 T3 和 Wnt 之间的相互作用在肠、垂体和肾脏中众所周知，但从未在骨骼中进行过研究。初步研究表明，骨形成细胞（成骨细胞）中的 Wnt 信号传导因 T3 的反应而减少。伦敦帝国理工学院 MRC 临床科学中心的 Moira Cheung 博士和 Graham Williams 教授将研究甲状腺激素如何抑制 Wnt 信号传导来调节成骨细胞活性。他们将确定： o Wnt 通路的哪些成分受 T3 调节 o T3 与成骨细胞中 Wnt 通路之间的相互作用 o T3 受体是否与 Wnt 的重要成分相互作用 了解 T3 对骨骼的作用机制非常重要，因为它可能会带来骨质疏松症的新治疗方法，骨质疏松症每年会导致超过 230,000 例骨折，导致 NHS 花费超过 17 亿英镑。