Osteogenic actions of phenytoin in human bone cells are mediated in part by TGF-beta 1

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
O NakadeK H Lau

Abstract

We have recently demonstrated that phenytoin, a widely used therapeutic agent for seizure disorders, has osteogenic effects in rats and in humans in vivo, and in human bone cells in vitro. The goal of the present study was to determine the mechanism of the osteogenic action of phenytoin in normal human mandible-derived bone cells. Because many osteogenic agents increased bone cell proliferation through mediation by growth factors, we tested the hypothesis that the osteogenic effects of phenytoin involved the release of a growth factor by measuring the mRNA level of several bone cell growth factors and insulin-like growth factor (IGF) binding proteins with Northern blots using specific cDNA probes. Treatment with 5-50 microM phenytoin reproducibly and markedly increased (up to 6-fold, p < 0.001) the mRNA of transforming growth factor (TGF)-beta 1, but not that of other growth factors (i.e., IGF-II, platelet-derived growth factor-A [PDGF-A], PDGF-B, and TGF-beta 2) and IGF binding proteins (i.e., IGFBP-3, -4, and -5). The stimulation was dose dependent, with an optimal dose of 10-50 microM. Maximal increase was seen after 1 h of phenytoin treatment. The release of biologically active TGF-beta activity in conditioned media was mea...Continue Reading

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Citations

May 5, 2004·Epilepsy & Behavior : E&B·Lorraine A Fitzpatrick
Jan 17, 2012·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Helen E GruberJames F Kellam
Mar 3, 2021·Reports of Biochemistry & Molecular Biology·Mitra Asgharian-RezaeeZahra Tayarani-Najaran

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