Grant: Operating Grant

Osteoporosis is characterized by bone loss, bone fragility and increased prevalence of fractures. It is a disease hindering the lives of close 2 million Canadians. Osteoporosis and related fractures results in loss of mobility, increased pain and dramatically compromised quality of life. The cost of treating osteoporosis related fractures and immobility is close to 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. Achieving high bone mass at younger age protects from bone loss occurring later in life. Bones are composed of cells and substance between cells called the extracellular matrix which is mostly collagen and mineral. Collagen is produced by resident cells, and in bones it undergoes a stabilization process that is required for proper bone cell function. We have discovered that transglutaminase-enzymes, TG2 and Factor XIIIA, are responsible for this matrix stabilization. Mice lacking these enzymes develop osteporosis and have low bone mass. In this proposal we plan to further explore how these two enzymes jointly promote bone cell activity. Our specific aims are: 1) to complete our analysis of the bones lacking these two enzymes; 2) to study the role of TG2 in bone cell attachment to bone; 3) to study a newly discovered form of FXIIIA on bone cell surface; 4) to study how matrix stabilization occurs in detail and molecular level and how it can lead to better functioning bone cells. From this work we hope to understand how also human bone tissue is made and assembled and how bone cell activity could be given a boost via therapeutics in osteoporosis to maintain optimal bone formation activity thoughout life.