Nutritional factors and interactions in musculoskeletal biology

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The long-term objective of my basic research program is to formulate new knowledge and training of skilled professionals in the biology of bone as influenced by nutrition. The short-term objectives will be completed over the next 5 years in rodent models to identify whole body and local mechanisms by which omega-3 fats increase bone density. This work is very new compared to the longstanding knowledge that calcium and vitamin D play important roles in skeletal biology. Vitamin D is used to make a hormone called calcitriol which controls bone metabolism by binding to receptors in the core of bone cells, called the nucleus where genes are located. Interestingly, an omega-3 fat called docosahexanoic acid (or DHA for short) commonly obtained from fatty fish is also linked to stronger bones. This is even after accounting for the important roles of dietary calcium and vitamin D. We now wish to prove that DHA also binds to receptors in the nucleus of bone cells and that this is how it regulates genes related to bone biology. From our previous studies, DHA works by reducing bone loss and in our recent work it seems to increase bone formation in association with more muscle  mass. Scientists need to understand how the body uses this omega fat to enhance bone and muscle as it will lead to further discovery. This question is the rationale for this NSERC Discovery grant. To explore the ways that DHA alters bone and muscle, small amounts of DHA are fed to various animal species for 3 months. At the beginning and end of the study, non-invasive x-ray techniques are used to create images of the skeleton and the inside of bones such as the leg bone. These x-rays also quantify how much mineral is packed into bone as well as the amount of muscle mass. Other techniques are used to show which proteins are altered in bone using microscopes and by measuring which genes are turned on. Tiny blood samples are taken from a leg vein and measured for DHA plus hormones and proteins that are delivered to bone where they act. Factors released from muscle to the surface of bone will be examined. Bone cells grown in the laboratory will be used to prove that DHA works through a "lock and key" system. Nuclear receptor proteins that bind DHA in bone will be blocked by using drugs that bind to the receptor and prevent the action of DHA. This research is novel since no researcher has yet discovered how DHA works in bone and in response to enhanced muscle mass. Knowing answers to this question is important since for years calcium and vitamin D has been the mainstay of nutrition and bone biology. Learning about novel nutrients will bring new understanding in nutrition and how bone cells work. As a research training program, many highly qualified young professionals will be trained over five years using highly sophisticated technology. Such training will enable successful research careers in industry, academia or government where this knowledge, skill and similar technology are highly sought after.