EL Wilson
Anti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells
Wilson, EL; Garton, M; Fuller, H
Abstract
Phenytoin is an antiepileptic drug used in the management of partial and tonic-clonic seizures. In previous studies we have shown that valproate, another antiepileptic drug, reduced the amount of two key bone proteins, pro-collagen I and osteonectin (SPARC, BM-40), in both skin fibroblasts and cultured osteoblast-like cells. Here we show that phenytoin also reduces pro-collagen I production in osteoblast-like cells, but does not appear to cause a decrease in osteonectin message or protein production. Instead, a 24 h exposure to a clinically relevant concentration of phenytoin resulted in a dose-dependent change in electrophoretic mobility of osteonectin, which was suggestive of a change in post-translational modification status. The perturbation of these important bone proteins could be one of the mechanisms to explain the bone loss that has been reported following long-term treatment with phenytoin.
Citation
Wilson, E., Garton, M., & Fuller, H. (2016). Anti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells. Epilepsy Research, 97-101. https://doi.org/10.1016/j.eplepsyres.2016.03.002
Acceptance Date | Mar 10, 2016 |
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Publication Date | Mar 11, 2016 |
Journal | Epilepsy Research |
Print ISSN | 0920-1211 |
Publisher | Elsevier |
Pages | 97-101 |
DOI | https://doi.org/10.1016/j.eplepsyres.2016.03.002 |
Keywords | epilepsy, drug therapy; phenytoin; valproate; collagen; osteonectin; SPARC; AEDs; anti-epileptic drugs; bone |
Publisher URL | https://doi.org/10.1016/j.eplepsyres.2016.03.002 |
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Publisher Licence URL
https://creativecommons.org/licenses/by-nc-nd/4.0/
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