Prior to the formation of calcified bone, noncollagenous proteins form in the extracellular bone matrix. Gamma-carboxyglutamic acid residues are formed by vitamin K, vitamin-D regulated calcium binding proteins containing residues of Gla. These residues are essential for the binding of calcium and constitue 1-2% of total bone protein. Osteocalcin itself binds strongly to apatite and calcium. Production of osteocalcin is expressed late in normal bone development and is characteristic of mature osteoblasts. Regular osteocalcin production has been shown to be linked to the p53 tumor suppressor gene. The p53 gene undergoes rearrangement in a high percentage of osteosarcomas, resulting in loss of its expression. The loss of p53 regulation inhibits further osteocalcin production. The absence of end-point differentiation in bone due to p53 rearrangements and lack of osteocalcin production may contribute to the maintenance of the tumorigenic phenotype in osteosarcomas.
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