Specificity Protein 7 Is Required for Proliferation and Differentiation of Ameloblasts and Odontoblasts.
Specificity Protein 7 Is Required for Proliferation and Differentiation of Ameloblasts and Odontoblasts.
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DOI：
10.1002/jbmr.3401
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Javed A
中科院分区：
文献类型：
--
作者：
Bae JM;Clarke JC;Rashid H;Adhami MD;McCullough K;Scott JS;Chen H;Sinha KM;de Crombrugghe B;Javed A
Sp 7/Osterix转录因子对骨发育至关重要。人类Sp 7基因突变与颅面畸形和骨生成异常有关。然而，Sp 7在胚胎牙齿发育中的作用仍然未知。在这里，我们确定了牙本质合成和牙齿发育的Sp 7的功能需求。Sp 7基因敲除小鼠表现出颅面畸形，牙槽骨完全缺失。令人惊讶的是，最初的牙齿形态发生正常进展Sp 7基因敲除小鼠。因此，牙槽骨的形成不是牙齿形态发生的先决条件。Sp 7是腭组织矿化所必需的，但对腭融合不是必需的。Sp 7缺陷的外胚间充质的增殖能力降低导致具有随机排列的立方形前成牙本质细胞和成牙本质细胞的小而畸形的牙齿。Sp 7促进成牙本质细胞的功能成熟和极化。成熟成牙本质细胞（Col 1a、Oc、Dspp、Dmp 1）和成釉细胞（Enam、Amelx、Mmp 20、Amtn、Klk 4）的标记物在Sp 7基因敲除小鼠的切牙和磨牙组织中几乎不表达。因此，牙本质和釉质基质是不存在的Sp 7无效的同窝仔。有趣的是，Sp 7的表达仅限于牙齿间充质细胞，表明对口腔上皮来源的成釉细胞的影响是细胞非自主的。在野生型小鼠的发育中的牙齿中注意到Fgf 3和Fgf 8配体的丰富表达。这两种配体在Sp 7缺失的切牙和磨牙中明显缺失，表明间充质和上皮之间的交叉信号传导被破坏。最后，启动子-报告基因测定显示Sp 7直接控制Fgf-配体的表达。总之，我们的数据表明，Sp 7是强制性的成釉细胞和成牙本质细胞的分化，但不是最初的牙齿形态发生。
The Sp7/Osterix transcription factor is essential for bone development. Mutations of the Sp7 gene in humans are associated with craniofacial anomalies and osteogenesis imperfecta. However, the role of Sp7 in embryonic tooth development remains unknown. Here we identified the functional requirement of Sp7 for dentin synthesis and tooth development. Sp7-null mice exhibit craniofacial dysmorphogenesis and are completely void of alveolar bone. Surprisingly, initial tooth morphogenesis progressed normally in Sp7-null mice. Thus the formation of alveolar bone is not a prerequisite for tooth morphogenesis. Sp7 is required for mineralization of palatal tissue but is not essential for palatal fusion. The reduced proliferative capacity of Sp7-deficient ectomesenchyme results in small and misshapen teeth with randomly arranged cuboidal preodontoblasts and preameloblasts. Sp7 promotes functional maturation and polarization of odontoblasts. Markers of mature odontoblast (Col1a, Oc, Dspp, Dmp1) and ameloblast (Enam, Amelx, Mmp20, Amtn, Klk4) are barely expressed in incisors and molar tissues of Sp7-null mice. Consequently, dentin and enamel matrix are absent in the Sp7-null littermates. Interestingly, the Sp7 expression is restricted to cells of the dental mesenchyme indicating the effect on oral epithelium–derived ameloblasts is cell-nonautonomous. Abundant expression of Fgf3 and Fgf8 ligand was noted in the developing tooth of wild-type mice. Both ligands were remarkably absent in the Sp7-null incisor and molar, suggesting cross-signaling between mesenchyme and epithelium is disrupted. Finally, promoter-reporter assays revealed that Sp7 directly controls the expression of Fgf-ligands. Together, our data demonstrate that Sp7 is obligatory for the differentiation of both ameloblasts and odontoblasts but not for the initial tooth morphogenesis.
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DOI：
10.1002/jbmr.2287
发表时间：
2014-12
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Chen H;Ghori-Javed FY;Rashid H;Adhami MD;Serra R;Gutierrez SE;Javed A
通讯作者：
Javed A
DOI：
10.1038/nrm3528
发表时间：
2013-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
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影响因子：
2.5
作者：
Li, Chun-Ying;Prochazka, Jan;Goodwin, Alice F.;Klein, Ophir D.
通讯作者：
Klein, Ophir D.
DOI：
10.1073/pnas.0910086106
发表时间：
2009-12-29
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
10.5
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