Grant: Operating Grant

Osteoporosis is characterized by low bone mass and deterioration of bone tissue. This silent disease progresses without symptoms and leads to bone fragility and increased risk of fractures, particularly of the hip, spine and wrist. According to Osteoporosis Canada fractures from osteoporosis are more common than heart attack, stroke and breast cancer combined. As people age, one in three women and one in five men will suffer from an osteoporotic fracture. Eighty percent of hip fractures are related to osteoporosis and result in death in 20% of cases, and disability in 50% of the survivors. The annual healthcare cost of treating osteoporosis and the fractures it causes has been estimated to be almost two billion dollars in Canada alone. Maintenance of bone mass and function depends upon the balance between bone breakdown and formation. Osteoclasts resorb (breakdown) bone and importantly osteoblasts build bone. Learning more about the functions of bone cells is required to identify new drug targets that may be beneficial for treatment of osteoporosis. We have been studying a protein called menin and found in tissue culture models that it is important for the generation and differentiation of the bone building cell - the osteoblast. We have now generated mouse models in which the level of menin is altered in mature osteoblasts. Lack of menin leads to reduced bone mass and abnormal bone structure in adult mice, whereas overexpression of menin leads to increased bone mass. Further studies are proposed to determine the key molecular signaling pathways that menin interacts with in the osteoblast. In addition, further mouse models that we have already generated in which menin expression is altered at earlier times in the life of the osteoblast - in progenitor stem cells and immature osteoblasts - will be investigated. This knowledge will be used to identify new drugs for improved treatment of bone diseases like osteoporosis.