The primary goals are to determine the composition and functional features of the Bone Matrix Unit, the supramolecular complex that calcifies, and how cells in the osteoblastic lineage regulate this process. Towards these aims, bone cell cultures were established for biochemical analysis, and for studies at the genomic level in collaboration with Drs. Marian F. Young and Larry W. Fisher. Intrinsic factors were found to influence the biosynthetic output of these cells such as the animal species, position within the cell cycle, and importantly, the developmental age of the donor. Each protein has a different pattern of expression with increasing age. Extrinsic factors (nutrient and factor levels, time in culture, cell density, attachment to different substrata) also affected cell metabolism. Bone cells and their products were compared to those from other tissues, and from patients with different diseases. By histochemistry, bone sialoprotein was found only in osteoblasts, certain hypertrophic chondrocytes, osteoclasts and trophoblasts of the placenta. Osteonectin, a major Ca++-binding bone protein, was found in renal epithelium, suggesting a role in ion transport. In cells from osteogenesis imperfecta patients, there were changes in post-translational modifications of not only collagen, but also proteoglycans, and in the absolute and relative amounts of the various components. These changes may cause the altered crystal structure found in OI bone, which ultimately results in fragility. In Turner's syndrome (karyotype 45, X0 and characterized by short stature and early onset osteoporosis), biglycan (whose gene is on the X chromosome) was found to be reduced by 50%. In various forms of osteosarcoma in rats and humans, both qualitative and quantitative differences in bone matrix proteins were detected, which may contribute to derangements in growth and structure observed in these tumors. Continued characterization of the interrelationship between bone cells and their extracellular environment will provide a clearer understanding of bone metabolism in health and in disease.
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