Anti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells.
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RJAH Orthopaedic Hospital; RJAH Orthopaedic NHS Foundation Trust; Keele UniversityPublication Date
2016-05-31
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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 24h 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. L., Garton, M., & Fuller, H. R. (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, 122, 97-101. doi:http://dx.doi.org/10.1016/j.eplepsyres.2016.03.002Publisher
ElsevierJournal
Epilepsy ResearchAdditional Links
http://www.ncbi.nlm.nih.gov/pubmed/26999801http://www.sciencedirect.com/science/article/pii/S0920121116300341
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ArticleLanguage
enEISSN
1872-6844ae974a485f413a2113503eed53cd6c53
10.1016/j.eplepsyres.2016.03.002
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