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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

Anti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells Thumbnail


Authors

EL Wilson

M Garton



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.

Acceptance Date Mar 10, 2016
Publication Date Mar 11, 2016
Publicly Available Date Mar 28, 2024
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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