Crosstalk between thyroid hormone and Wnt signalling in osteoblasts

甲状腺激素（T3）过量会导致骨质流失，尽管其潜在机制尚不清楚。骨中的关键细胞信号传导途径是“Wnt”途径。Wnt的抑制导致高骨转换，从而导致骨脆性和骨质疏松症，这种情况也会响应于T3过量而发生。相反，增加Wnt信号导致骨量增加，类似于T3缺乏对骨骼的影响。T3和Wnt之间的相互作用在肠、垂体和肾脏中是众所周知的，但从未在骨骼中进行过研究。初步研究表明，Wnt信号在骨形成细胞（成骨细胞）中响应于T3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威廉姆斯教授将研究甲状腺激素如何抑制Wnt信号以调节成骨细胞活性。他们将确定：o成骨细胞中T3和Wnt通路之间的相互作用o T3受体是否与Wnt通路的重要组分相互作用了解T3作用于骨的机制很重要，因为它可能导致骨质疏松症的新治疗方法，骨质疏松症是一种导致230多个，000骨折每年花费NHS超过17亿英镑。

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.