Crosstalk between thyroid hormone and Wnt signalling in osteoblasts

甲状腺激素(T3)过多会导致骨质流失，尽管其潜在的机制尚不清楚。骨骼中一条关键的细胞信号通路是“Wnt”通路。抑制Wnt会导致高骨转换，导致骨脆性和骨质疏松症，这种情况也会发生在对T3过剩的反应中。相反，Wnt信号的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道、脑下垂体和肾脏中广为人知，但在骨骼中从未被研究过。初步研究表明，骨形成细胞(成骨细胞)对T3的反应是Wnt信号减少。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信号来调节成骨细胞的活动。他们将确定：Wnt途径的哪些组成部分受成骨细胞中T3和Wnt途径之间的T3o相互作用调节，因此T3受体是否与Wnt途径的重要组成部分相互作用了解T3作用于骨骼的机制非常重要，因为它可能导致骨质疏松症的新治疗方法，这种疾病每年导致超过23万例骨折，NHS花费超过17亿GB。

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.