The relationship between Vitamin K and vitamin K-Dependent proteins and bone metabolism is not clearly understood. A vitamin K-dependent, bone specific protein of unknown function has been identified in all bones examined. This protein, called the bone Gla protein (BGP) or osteocalcin, is an abundant noncollagenous protein, and comprises approximately 1-2% of the total proteins present. Minute quantities are found in the circulation, and levels are altered in diseases such as osteoporosis and various metabolic bone diseases. In this application the role of vitamin K-dependent proteins in bone will be explored in experiments to: 1) Determine the number and relationship of all bone derived vitamin K dependent proteins, by searching for proteins antigenically related to BGP or which contain the vitamin K-dependent Gamma -carboxy glutamate. 2) Establish the sequence of events, and factors which control the biosynthesis and secretion of bone G1a protein using cloned rat osteosarcome cells. 3) Explore the localization and distribution of bone G1a protein in bone matrix using purified antibody and immunochemical methods, and 4) The potential role of bone G1a protein as an etiologic agent in genetic skeletal disorders. 5) Assess the synthesis of bone G1a protein by calf bone organ cultures and isolated calf bone cells and compare to the synthesis of bone collagen, and other noncollagenous proteins. 6) Investigatate the mechanism of degradation of bone G1a protein in an in vitro calf bone culture system. 7) Search for a second unique Gamma-carboxyglutamic acid containing protein of bone. These experiments are designed to provide insight into the biological function of one specific vitamin K dependent protein, as well as to understand the spectrum of effects of vitamin K on bone metabolism and physiology. The focussed understanding of the relationship of a bone protein to underlying bone metabolism may provide valuable biochemical insight for the management of problems such as osteoporosis, non-union fractures, and metabolic bone diseases.
