Grant: Project Grant

Osteoporosis is a disease that is characterized by low bone mass, bone fragility and increased prevalence of fractures. Osteoporosis hinders the life of over to 2 million Canadians and fractures cause loss of mobility, increased pain and dramatically compromised quality of life. The cost of treating osteoporosis related fractures and immobility is over 2 billion dollars each year and it is predicted that these numbers will keep increasing as Canadian population ages. The causes for osteoporosis can be linked to genetics, nutrition, medication, and it can occur at any time during life of both men and women. Bone mass is maintained by bone cells that renew bone in cycles of bone tissue removal and new bone formation. In osteoporosis, this cycle does not function properly and is tilted towards bone removal which leads to total decrease in bone mass and weakened bones. We have discovered that transglutaminase-enzymes are important regulators of bone tissue removal. Mice lacking transglutaminases develop osteoporosis, because bone cells do not function properly and produce biochemical that increase bone removal. In this proposal, we further explore how transglutaminases can cause the loss of bone mass and we will test if they can be targeted in osteoporosis in mice to correct the bone removal-formation balance. Our aims are to examine mechanisms how transglutaminases work inside bone cells and to test chemical inhibitors of transglutaminases as therapeutics in osteoporotic mice. From this work, we hope to understand how human bone tissue is formed and removed and how bone cell activity could be modulated in osteoporosis to maintain optimal bone formation activity and bone mass throughout life.