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

Hdl Handle:
http://hdl.handle.net/10034/610811
Title:
Anti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells.
Authors:
Wilson, Emma L.; Garton, Mark; Fuller, Heidi R.
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 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.
Affiliation:
RJAH Orthopaedic Hospital; RJAH Orthopaedic NHS Foundation Trust; Keele University
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.2016.03.002
Publisher:
Elsevier
Journal:
Epilepsy Research
Publication Date:
May-2016
URI:
http://hdl.handle.net/10034/610811
DOI:
10.1016/j.eplepsyres.2016.03.002
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/26999801; http://www.sciencedirect.com/science/article/pii/S0920121116300341
Type:
Article
Language:
en
EISSN:
1872-6844
Appears in Collections:
Institute of Medicine

Full metadata record

DC FieldValue Language
dc.contributor.authorWilson, Emma L.en
dc.contributor.authorGarton, Marken
dc.contributor.authorFuller, Heidi R.en
dc.date.accessioned2016-05-26T14:18:34Zen
dc.date.available2016-05-26T14:18:34Zen
dc.date.issued2016-05en
dc.identifier.citationWilson, 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.2016.03.002en
dc.identifier.doi10.1016/j.eplepsyres.2016.03.002-
dc.identifier.urihttp://hdl.handle.net/10034/610811en
dc.description.abstractPhenytoin 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.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/26999801en
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0920121116300341en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectEpilepsyen
dc.subjectBone lossen
dc.subjectOsteonectinen
dc.subjectSPARCen
dc.titleAnti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells.en
dc.typeArticleen
dc.identifier.eissn1872-6844en
dc.contributor.departmentRJAH Orthopaedic Hospital; RJAH Orthopaedic NHS Foundation Trust; Keele Universityen
dc.identifier.journalEpilepsy Researchen
dc.date.accepted2016-03-10en
or.grant.openaccessYesen
rioxxterms.funderInstitute of Orthopaedics plcen
rioxxterms.identifier.projectI don't have a university code since the research was carried out in an NHS trust using funding from a small charityen
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2017-06-01en
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