Crosstalk between thyroid hormone and Wnt signalling in osteoblasts

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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.