Does AMP Kinase signalling contribute to skeletal health?. (360G-Wellcome-086630_Z_08_Z)

New studies have established a hormonal link between bone remodelling, food intake, and energy metabolism. We recently identified a neuroendocrine activation of AMP-activated kinase (AMPK) in bone cells. AMPK is a sensor and regulator of energy balance in the cell, but also at the whole body level where it integrates nutritional and hormonal signals in the central nervous system and peripheral tissues. We hypothesise that AMPK signalling stimulates bone formation and inhibits bone resorption and that AMPK activity in bone cells is regulated by the same hormones and neuromediators that control energy homeostasis, providing one molecular link between bone mass and energy metabolism. Our aims are to identify the direct metabolic activators of AMPK in bone cells, to determine whether AMPK activity is involved in bone cell differentiation and function, and to establish which are the specific transcriptional targets regulated by AMPK in bone cells. As antidiabetic drugs (metformin and thiazo lidinediones) can modulate AMPK and thiazolidinediones have deleterious effects on bone mass, we will also examine whether AMPK signalling mediates the skeletal effects of these drugs. A better understanding of the mechanisms linking osteoporosis to other metabolic disorders is likely to lead to new therapies for those diseases.