University of Connecticut School of Dental Medicine, Farmington, CT, USA.
NYU Langone Health, Postdoctoral Pediatric Dentistry Program, Brooklyn, NY, 11220, USA.
Calcif Tissue Int. 2022 Jan;110(1):93-103. doi: 10.1007/s00223-021-00888-3. Epub 2021 Jul 10.
Transgenic mice overexpressing human high molecular weight fibroblast growth factor 2 (HMWFGF2) isoforms in osteoblast and odontoblast lineages (HMWTg) exhibit decreased dentin and alveolar bone mineralization, enlarged pulp chamber, and increased fibroblast growth factor 23 (FGF23). We examined if the alveolar bone and dentin mineralization defects in HMWTg mice resulted from increased FGF23 expression and whether an FGF23 neutralizing antibody could rescue the hypomineralization phenotype. HMWTg and VectorTg control mice were given subcutaneous injections of FGF23 neutralizing antibody twice/week starting at postnatal day 21 for 6 weeks. Since Calcitriol (1,25D) have direct effects in promoting bone mineralization, we also determined if 1,25D protects against the defective dentin and alveolar bone mineralization. Therefore, HMWTg mice were given subcutaneous injections of 1,25D daily or concomitantly with FGF23 neutralizing antibody for 6 weeks. Our results showed that HMWTg mice displayed thickened predentin, alveolar bone hypomineralization, and enlarged pulp chambers. FGF23 neutralizing antibody and 1,25D monotherapy partially rescued the dentin mineralization defects and the enlarged pulp chamber phenotype in HMWTg mice. 1,25D alone was not sufficient to rescue the alveolar bone hypomineralization. Interestingly, HMWTg mice treated with both FGF23 neutralizing antibody and 1.25D further rescued the enlarged pulp chamber size, and dentin and alveolar bone mineralization defects. We conclude that the dentin and alveolar bone mineralization defects in HMWTg mice might result from increased FGF23 expression. Our results show a novel role of HMWFGF2 on dentoalveolar mineralization.
过表达人高分子量成纤维细胞生长因子 2（HMWFGF2）同种型的转基因小鼠在成骨细胞和成牙本质细胞谱系中（HMWTg）表现出牙本质和牙槽骨矿化减少、牙髓腔增大和成纤维细胞生长因子 23（FGF23）增加。我们检查了 HMWTg 小鼠的牙槽骨和牙本质矿化缺陷是否是由于 FGF23 表达增加引起的，以及 FGF23 中和抗体是否可以挽救低矿化表型。从出生后第 21 天开始，HMWTg 和 VectorTg 对照小鼠每周两次皮下注射 FGF23 中和抗体，持续 6 周。由于 1,25-二羟维生素 D3（Calcitriol）具有直接促进骨矿化的作用，我们还确定了 1,25D 是否可以防止牙本质和牙槽骨矿化缺陷。因此，HMWTg 小鼠每天或同时皮下注射 1,25D 和 FGF23 中和抗体持续 6 周。我们的结果表明，HMWTg 小鼠表现出牙本质增厚、牙槽骨矿化减少和牙髓腔增大。FGF23 中和抗体和 1,25D 单独治疗部分挽救了 HMWTg 小鼠的牙本质矿化缺陷和牙髓腔增大表型。1,25D 单独不足以挽救牙槽骨矿化减少。有趣的是，同时使用 FGF23 中和抗体和 1.25D 治疗的 HMWTg 小鼠进一步挽救了增大的牙髓腔大小以及牙本质和牙槽骨矿化缺陷。我们得出结论，HMWTg 小鼠的牙本质和牙槽骨矿化缺陷可能是由于 FGF23 表达增加引起的。我们的结果表明 HMWFGF2 在牙本质牙槽骨矿化中的新作用。
