Our goal is to understand the biological function of the vitamin K dependent protein, bone Gla protein, which we have discovered in mammalian bone. Toward this end, we plan experiments to explore the altered structure and physiological function of rabbit bone which has been made selectively deficient in Gla protein by the use of a unique Warfarin plus coagulation factor injection procedure we have developed. We also intend to investigate further the dramatic 1000-fold increase in weight percent of rat Gla protein which we have recently discovered occurs in the first two weeks after birth. Major problems to be investigated with the Gla protein deficient bone systems include the following: 1. Bone resorption in response to a calcium deficient diet and subsequent reformation of new bone when the diet is returned to normal. 2. Fracture repair, including histological and biomechanical tests of union. 3. Bone structure, including the nature and amount of bone mineral, biomechanical strength tests and histological structure. 4. Immunohistological localization of bone Gla protein, including identification of the cells which make the protein, its location in bone matrix, and the time it first appears in the formation of new bone. 5. Biosynthesis of the bone Gla protein in rat calvarial culture, including investigations into the possible formation of Gla protein by proteolytic processing of a precursor.
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