Triiodothyronine, a Regulator of Osteoblastic Differentiation: Depression of Histone H4, Attenuation of c-fos/c-jun, and Induction of Osteocalcin Expression |
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Authors: | F Varga M Rumpler E Luegmayr N Fratzl-Zelman H Glantschnig K Klaushofer |
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Institution: | (1) Ludwig Boltzmann-Institute of Osteology, 4th Medical Department, Hanusch Hospital, Heinrich Collinstrasse 30, A-1140 Vienna, Austria, AT |
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Abstract: | Thyroid hormones influence growth and differentiation of bone cells. In vivo and in vitro data indicate their importance for development and maintenance of the skeleton. Triiodothyronine (T3) inhibits proliferation
and accelerates differentiation of osteoblasts. We studied the regulatory effect of T3 on markers of proliferation as well
as on specific markers of the osteoblastic phenotype in cultured MC3T3-E1 cells at different time points. In parallel to the
inhibitory effect on proliferation, T3 down-regulated histone H4 mRNA expression. Early genes (c-fos/c-jun) are highly expressed
in proliferating cells and are down-regulated when the cells switch to differentiation. When MC3T3-E1 cells are cultured under
serum-free conditions, basal c-fos/c-jun expressions are nearly undetectable. Under these conditions, c-fos/c-jun mRNAs can
be stimulated by EGF, the effect of which is attenuated to about 46% by T3. In addition, T3 stimulated the expression at the
mRNA and protein level of osteocalcin, a marker of mature osteoblasts and alkaline phosphatase activity. All these effects
were more pronounced when cells were cultured for more than 6 days. These data indicate that T3 acts as a differentiation
factor in osteoblasts by influencing the expression of cell cycle–regulated, of cell growth–regulated, and of phenotypic genes.
Received: 10 May 1996 / Accepted: 5 June 1997 |
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Keywords: | : Triiodothyronine — MC3T3-E1 cells — c-fos — Osteocalcin — Histone H4 |
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