Owen, Thomas A. and Aronow, Michael and Shalhoub, Victoria and Barone, Leesa M. and Wilming, Laurens and Tassinari, Melissa S. and Kennedy, Mary Beth and Pockwinse, Shirwin and Lian, Jane B. and Stein, Gary S. (1990) Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. Journal of Cellular Physiology, 143 (3). pp. 420-430. ISSN 0021-9541 http://resolver.caltech.edu/CaltechAUTHORS:20120424-154233072
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The relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation was examined in primary diploid cultures of fetal calvarial derived osteoblasts by the combined use of autoradiography, histochemistry, biochemistry, and mRNA assays of osteoblast cell growth and phenotypic genes. Modifications in gene expression define a developmental sequence that has 1) three principle periods--proliferation, extracellular matrix maturation, and mineralization--and 2) two restriction points to which the cells can progress but cannot pass without further signals--the first when proliferation is down-regulated and gene expression associated with extracellular matrix maturation is induced, and the second when mineralization occurs. Initially, actively proliferating cells, expressing cell cycle- and cell growth-regulated genes, produce a fibronectin/type I collagen extracellular matrix. A reciprocal and functionally coupled relationship between the decline in proliferative activity and the subsequent induction of genes associated with matrix maturation and mineralization is supported by 1) a temporal sequence of events in which there is an enhanced expression of alkaline phosphatase immediately following the proliferative period, and later, an increased expression of osteocalcin and osteopontin at the onset of mineralization; 2) increased expression of a specific subset of osteoblast phenotype markers, alkaline phosphatase and osteopontin, when proliferation is inhibited by hydroxyurea; and 3) enhanced levels of expression of the osteoblast markers as a function of ascorbic acid-induced collagen deposition, suggesting that the extracellular matrix contributes to both the shutdown of proliferation and the development of the osteoblast phenotype.
|Additional Information:||© 1990 Wiley-Liss, Inc. Received December 19, 1989; accepted February 9, 1990. Article first published online: 4 Feb. 2005. We thank Marie Giorgio for photographic assistance. These studies were supported by grants from the National Institutes of Health (GM32010, GM32381, AR35166, AR39122, HD22400), the National Science Foundation (DCB88-96116), the March of Dimes Birth Defects Foundation (1-813), and the International Life Sciences Institute (Washington, DC).|
|Official Citation:||Owen, T. A., Aronow, M., Shalhoub, V., Barone, L. M., Wilming, L., Tassinari, M. S., Kennedy, M. B., Pockwinse, S., Lian, J. B. and Stein, G. S. (1990), Progressive development of the rat osteoblast phenotype in vitro: Reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J. Cell. Physiol., 143: 420–430. doi: 10.1002/jcp.1041430304|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Melanie Stefan|
|Deposited On:||25 Apr 2012 16:50|
|Last Modified:||25 Apr 2012 16:50|
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