National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
J Dent Res. 2014 Feb;93(2):148-54. doi: 10.1177/0022034513516344. Epub 2013 Dec 11.
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.
钙磷稳态是通过激素(包括 1,25(OH)2D3 (1,25D)、甲状旁腺激素和成纤维细胞生长因子 23 (FGF23))的相互作用及其与其他蛋白的相互作用来实现的。例如,牙本质基质蛋白 1 (DMP-1)的突变会导致 FGF23 增加和低磷性佝偻病。有报道称 1,25D 可调节 FGF23;因此,我们假设 1,25D 可能在中间步骤中参与调节 DMP-1。已知表达 DMP-1 的鼠类成牙骨质细胞 (OCCM-30)和成骨细胞样细胞 (MLO-Y4 和 MLO-A5) 用于分析 1,25D 对体外 DMP-1 表达的影响。在所有细胞类型中,1,25D 的存在使 DMP-1 的 mRNA 水平降低了 50%(p<0.05),而使用维生素 D 受体 (VDR) 激动剂 (EB1089) 和拮抗剂 (23S,25S)-DLAM-2P 证实了 VDR 途径的激活是必需的。进一步的分析表明,组蛋白去乙酰化酶募集是必需的,但蛋白激酶 A 和 C 途径都不是必需的。总之,我们的结果支持了 1,25D 通过 VDR 依赖性机制调节 DMP-1 表达的假设,这可能有助于局部骨骼/牙齿矿物质稳态的变化。