title: Valproate reduces collagen and osteonectin in cultured bone cells.
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 24h 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.
authors.affiliation: Wolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry SY10 7AG, United Kingdom.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Humphrey
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Morris
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Fuller
mesh_terms: D000927:Anticonvulsants / Q000494:pharmacology*; D015153:Blotting, Western; D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D015676:Osteonectin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D024042:Collagen Type I; D034904:Lamin Type A; D015676:Osteonectin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014635:Valproic Acid
keywords: Bone; Collagen; HDAC; Osteonectin; Valproate; hFOB1.19