Journal of Dental Research · 2013 · 34 citations · 25 references
MedicineEndocrinologyOral BiologyBone MetabolismCalcium HomeostasisDentin BiologyBone FormationDentin MineralizationOsteocyte BiologyOsteogenesisPhosphate HomeostasisVitamin DBone Mineral HomeostasisCementocyte BiologyDentin Matrix Protein 1 ExpressionDentin Matrix Protein ExpressionFibroblast Growth Factor 23 DysregulationHereditary Hypophosphatemic RicketsVitamin D Effects On BoneVitamin D Receptor Interactions
Hormonal regulation of calcium and phosphorus homeostasis involves 1,25‑vitamin D, PTH, and FGF23, and mutations in dentin matrix protein 1 (DMP‑1) raise FGF23 levels and cause hypophosphatemic rickets. The study tested whether 1,25‑vitamin D modulates DMP‑1 expression through an intermediary step. Murine cementoblasts (OCCM‑30) and osteocyte‑like cells (MLO‑Y4, MLO‑A5) were treated with 1,25‑vitamin D to assess its effect on DMP‑1 mRNA in vitro. 1,25‑vitamin D reduced DMP‑1 mRNA by 50 % in all cell types via a VDR‑dependent pathway that required histone deacetylase recruitment but not PKA or PKC, supporting a role for vitamin D in local bone/tooth mineral homeostasis.
Calcium and phosphorus homeostasis is achieved by interplay among hormones, including 1,25(OH) 2 D 3 (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.
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Establishment of an Osteocyte-like Cell Line, MLO-Y4
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