title: Vitamin D represses dentin matrix protein 1 in cementoblasts and osteocytes.
abstract: Calcium and phosphorus homeostasis is achieved by interplay among hormones, including 1,25(OH)2D3 (1,25D), parathyroid hormone, and fibroblast growth factor 23 (FGF23), and their interactions with other proteins. For example, mutations in dentin matrix protein 1 (DMP-1) result in increased FGF23 and hypophosphatemic rickets. 1,25D is reported to modulate FGF23; thus, we hypothesized that 1,25D may be involved in modulating DMP-1 in an intermediary step. Murine cementoblasts (OCCM-30) and osteocyte-like cells (MLO-Y4 and MLO-A5), known to express DMP-1, were used to analyze effects of 1,25D on DMP-1 expression in vitro. DMP-1 mRNA levels decreased by 50% (p < .05) in the presence of 1,25D in all cell types, while use of a vitamin D receptor (VDR) agonist (EB1089) and antagonist (23S,25S)-DLAM-2P confirmed that VDR pathway activation was required for this response. Further analysis showed that histone deacetylase recruitment was necessary, but neither protein kinase A nor C pathways were required. In conclusion, our results support the hypothesis that 1,25D regulates DMP-1 expression through a VDR-dependent mechanism, possibly contributing to local changes in bone/tooth mineral homeostasis.
authors: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: F H
authors: FH
authors: Nociti
authors: B L
authors: BL
authors: Foster
authors: A B
authors: AB
authors: Tran
authors: D
authors: D
authors: Dunn
authors: R B
authors: RB
authors: Presland
authors: L
authors: L
authors: Wang
authors: N
authors: N
authors: Bhattacharyya
authors: M T
authors: MT
authors: Collins
authors: M J
authors: MJ
authors: Somerman
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002460:Cell Line; D003739:Dental Cementum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004963:Estrenes / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D010011:Osteocytes / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000819:agonists / Q000037:antagonists & inhibitors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014815:Vitamins / Q000494:pharmacology*; D000077337:Vorinostat
chemical_list: C513308:Dmp1 protein, mouse; D004963:Estrenes; D016326:Extracellular Matrix Proteins; C000717428:Fgf23 protein, mouse; D005419:Flavonoids; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D008301:Maleimides; D011760:Pyrrolidinones; D018167:Receptors, Calcitriol; D014815:Vitamins; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D000077337:Vorinostat; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases; D006655:Histone Deacetylases; D002117:Calcitriol; C070515:bisindolylmaleimide I; C078903:seocalcitol; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: SIBLING family; Vitamin D receptor; fibroblast growth factor 23; osteogenesis; phosphate homeostasis; phosphate regulating endopeptidase homolog