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Critical Reviews in Oral Biology & Medicine, Vol 3, 269-305, Copyright © 1992 by International & American Associations for Dental Research
ARTICLES |
J. B. Lian and G. S. Stein
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655.
The combined application of molecular, biochemical, histochemical, and ultrastructural approaches has defined a temporal sequence of gene expression associated with development of the bone cell phenotype in primary osteoblast cultures. The peak levels of expressed genes reflect a developmental sequence of bone cell differentiation characterized by three principal periods: proliferation, extracellular matrix maturation and mineralization, and two restriction points to which the cells can progress but cannot pass without further signals. The regulation of cell growth and bone-specific gene expression has been examined during this developmental sequence and is discussed within the context of several unique concepts. These are (1) that oncogene expression in proliferating osteoblasts contributes to the suppression of genes expressed postproliferatively, (2) that hormone modulation of a gene is dependent upon the maturational state of the osteoblast, and (3) that chromatin structure and the presence of nucleosomes contribute to three-dimensional organization of gene promoters that support synergistic and/or antagonistic activities of physiologic mediators of bone cell growth and differentiation.
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