Department of Stomatology, Hospital Affiliated to Binzhou Medical University, Binzhou City, Shandong Province, 256603, People's Republic of China.
Binzhou People's Hospital of Shandong Province, Shandong Binzhou 2566610, People's Republic of China.
Arch Oral Biol. 2018 Dec;96:146-154. doi: 10.1016/j.archoralbio.2018.09.003. Epub 2018 Sep 12.
In order to understand the specific in vivo function of transforming growth factor-beta1 (TGF-β1), we successfully established aTGF-β1 deficient mouse model using a conditional knockout method. In the present study, we aimed to further understand the potential role of TGF-β1 in enamel formation.
Transgenic mice withoutTGF-β1 in epithelial cells were generated. Scanning electron microscopy and micro-computed tomography analysis were used to detect the dental appearance, enamel microstructure and tooth density. Histological analysis was used to examine the residual organic matrix of enamel. Quantitative real-time polymerase chain reaction was used to analyze the expressions of enamel matrix proteins at the mRNA level.
The enamel of mandibular molars and incisors inTGF-β1 conditional knockout mice displayed severe attrition and lower density compared with the wild-type littermates. A slender microstructure of enamel rod was observed, and enamel matrix proteins were retained in the enamel space at the maturation stage in conditional knockout mice. Moreover, the expressions of enamel matrix protein-encoding genes, such as amelogenin (Amelx), ameloblastin (Ambn), Enamelin (Enam) and matrix metalloproteinase-20 (Mmp-20), were increased in enamel organs of conditional knockout mice. On the other hand, the expressions of Amelotin (Amtn), kallikrein-related peptidase-4 (Klk4), C4orf26 and WD repeat-containing protein 72 (Wdr72) were dramatically decreased at the transition and maturation stages.
TGF-β1 played an important role in enamel mineralization through decreasing synthesis ofAmelx, Ambn and Enam and increasing synthesis of Klk4, Amtn, Corf26 and Wdr72.
为了了解转化生长因子-β1(TGF-β1)的具体体内功能,我们使用条件性基因敲除方法成功建立了 TGF-β1 缺陷型小鼠模型。本研究旨在进一步了解 TGF-β1 在釉质形成中的潜在作用。
生成上皮细胞中无 TGF-β1 的转基因小鼠。扫描电子显微镜和微计算机断层扫描分析用于检测牙齿外观、釉质微观结构和牙齿密度。组织学分析用于检查釉质残留的有机基质。实时定量聚合酶链反应用于分析釉质基质蛋白在 mRNA 水平上的表达。
TGF-β1 条件性基因敲除小鼠下颌磨牙和切牙的釉质显示出严重的磨损和较低的密度,与野生型同窝仔相比。在条件性基因敲除小鼠中观察到釉质杆的细长微观结构,并且在成熟阶段釉质空间中保留了釉质基质蛋白。此外,釉质基质蛋白编码基因如釉原蛋白(Amelx)、釉基质蛋白(Ambn)、釉蛋白(Enam)和基质金属蛋白酶-20(Mmp-20)的表达在条件性基因敲除小鼠的釉质器官中增加。另一方面,釉质小体蛋白(Amtn)、激肽释放酶相关肽酶-4(Klk4)、C4orf26 和 WD 重复蛋白 72(Wdr72)的表达在过渡和成熟阶段急剧下降。
TGF-β1 通过减少 Amelx、Ambn 和 Enam 的合成和增加 Klk4、Amtn、Corf26 和 Wdr72 的合成,在釉质矿化中发挥重要作用。