Valproate reduces collagen and osteonectin in cultured bone cells

Humphrey, Emma L.; Morris, Glenn E.; Fuller, Heidi R.

Abstract

Valproate is a histone deacetylase (HDAC) inhibitor that was introduced more than 40 years ago and is commonly used to treat epilepsy and mood disorders. Its long-term side effects can include bone loss, although the exact mechanism for this is currently unknown. In a previous study, we used iTRAQ labelling and mass spectrometry to profile the effect of valproate on skin fibroblast cells. We found, for the first time, that valproate reduced the amount of two key bone proteins; collagen I and osteonectin (SPARC, BM-40) while over 1000 other proteins remained unchanged (Fuller et al., 2010). We now show that valproate treatment also reduces the protein levels of collagen I and osteonectin in the hFOB1.19 osteoblast-like cell line. Pro-collagen I was reduced by 48% and osteonectin by 25% after 24 h exposure to a clinically-relevant concentration of valproate. Collagen I is the main protein component of bone matrix and osteonectin has a major role in bone development and mineralisation, so reduced levels may contribute to bone loss following long-term in vivo exposure to valproate.

Citation

Humphrey, E. L., Morris, G. E., & Fuller, H. R. (2013). Valproate reduces collagen and osteonectin in cultured bone cells. Epilepsy Research, 106(3), 446-450. https://doi.org/10.1016/j.eplepsyres.2013.06.011

• Journal Article Type: Article
• Acceptance Date: Jun 28, 2013
• Online Publication Date: Jul 29, 2013
• Publication Date: 2013-10
• Deposit Date: Jun 13, 2023
• Journal: Epilepsy Research
• Print ISSN: 0920-1211
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 106
• Issue: 3
• Pages: 446-450
• DOI: https://doi.org/10.1016/j.eplepsyres.2013.06.011
• Keywords: Neurology (clinical); Neurology; Valproate; Collagen; Osteonectin; Bone; HDAC; hFOB1.19
• Additional Information: This article is maintained by: Elsevier; Article Title: Valproate reduces collagen and osteonectin in cultured bone cells; Journal Title: Epilepsy Research; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.eplepsyres.2013.06.011; Content Type: article; Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.