Ablation of Runx2 in Ameloblasts Suppresses Enamel Maturation in Tooth Development.
Ablation of Runx2 in Ameloblasts Suppresses Enamel Maturation in Tooth Development.
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成釉细胞中 Runx2 的消融抑制牙齿发育过程中牙釉质的成熟
DOI：
10.1038/s41598-018-27873-5
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发表时间：
2018-06-25
影响因子：
4.6
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Chu Q;Gao Y;Gao X;Dong Z;Song W;Xu Z;Xiang L;Wang Y;Zhang L;Li M;Gao Y
矮小相关转录因子2(Runx2)参与牙齿发育的早期。然而，很少有研究报道Runx2在釉质发育中的作用，这可能归因于Runx2全基因敲除小鼠在出生后无法存活。在本研究中，我们使用条件性基因敲除(CKO)方法成功地建立了Runx2缺陷小鼠模型。我们观察到CKO小鼠牙釉质矿化程度和釉质棒大小显著降低。组织学分析显示，CKO磨牙成熟期釉质层中有釉质蛋白残留。进一步的QRT-PCR分析表明，釉原蛋白(AMELX)、成釉蛋白(AMBN)和成釉蛋白(ENAM)等编码釉质结构蛋白的基因在CKO釉质器官中的表达增加。另一方面，从分泌晚期到成熟期，激肽释放酶相关多肽酶-4(KLK4)在mRNA和蛋白水平的表达显著降低，而基质金属蛋白酶-20(MMP-20)的表达无明显变化。最后，免疫组织化学显示，CKO小鼠成釉细胞对成釉蛋白的摄取显著减少。综上所述，Runx2通过增加KLK4的合成，减少AMELX、AMBN和ENAM的合成，从而控制釉质的成熟。
Runt-related transcription factor 2 (Runx2) is involved in the early stage of tooth development. However, only few studies have reported the role of Runx2 in enamel development, which may be attributed to thatRunx2full knockout mice cannot survive after birth. In the present study, we successfully established a Runx2-deficient mouse model using a conditional knockout (cKO) method. We observed a significant reduction in the degree of mineralization and the decreased size of enamel rods in cKO mice. Histological analysis showed the retained enamel proteins in enamel layer at maturation stage in cKO molars. Further analysis by qRT-PCR revealed that the expressions of genes encoding enamel structure proteins, such as amelogenin (AMELX), ameloblastin (AMBN) and enamelin (ENAM), were increased in cKO enamel organs. On the other hand, the expression of kallikrein-related peptidase-4 (KLK4) at the mRNA and protein levels was dramatically decreased from late secretory stage to maturation stage in cKO enamel organs, while the expression of matrix metalloproteinase-20 (MMP-20) was not significantly altered. Finally, immunohistochemistry indicated that the uptake of amelogenins by ameloblasts was significantly decreased in cKO mice. Taken together, Runx2 played critical roles in controlling enamel maturation by increasing synthesis of KLK4 and decreasing synthesis of AMELX, AMBN and ENAM.
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影响因子：
3.5
作者：
Barron MJ;Brookes SJ;Kirkham J;Shore RC;Hunt C;Mironov A;Kingswell NJ;Maycock J;Shuttleworth CA;Dixon MJ
通讯作者：
Dixon MJ
影响因子：
3.1
作者：
Bruderer, M.;Richards, R. G.;Stoddart, M. J.
通讯作者：
Stoddart, M. J.
影响因子：
2.7
作者：
Hu, Jan C. -C.;Chun, Yong-Hee P.;Simmer, James P.
通讯作者：
Simmer, James P.
影响因子：
4
作者：
Smith CEL;Kirkham J;Day PF;Soldani F;McDerra EJ;Poulter JA;Inglehearn CF;Mighell AJ;Brookes SJ
通讯作者：
Brookes SJ
影响因子：
7.6
作者：
Gasse, B.;Karayigit, E.;Bloch-Zupan, A.
通讯作者：
Bloch-Zupan, A.