The decrease in bone mass associated with aging and the related syndrome of osteoporosis can be attributed to a defect associated with the inability of osteoblasts to synthesize new calcifiable matrix. We have shown a progressive decline in the bone forming capacity with increasing age in syngeneic rats. We would like to test whether a lack of osteoprogenitor cells or a lack of systemic factors for osteoblast differentiation or function is responsible for our observed result. The tools we have developed in the laboratory over the last 2 years will enable us to measure relevant parameters of osteogenesis. In vivo we shall study bone morphogenesis induced by demineralized bone matrix and bone formation within implanted diffusion chambers. Our in vitro systems are bone organ culture and bone marrow culture. As planned, we have developed expertise in the measurement of bone specific markers. We have established our own radioimmunoassay for bone Gla protein (Osteocalcin), further developed our ability to identify collagen types synthesized in vitro, and established alkaline phosphatase and calcium assays as a measure of bone formation in our system. We have also designed a novel method to induce bone using perforated bone matrix, and this method will answer questions concerning the importance and contribution of the 3 dimensional architecture of the bone matrix to be addressed. The studies outlined should provide insight into the basic molecular, cellular, and matrix interactions necessary for osteogenesis. We expect that they will also provide useful information for understanding the age-related degenerative diseases of bone.
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