Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation.
Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation.
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DOI：
10.1016/j.ydbio.2013.08.003
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发表时间：
2013-10-01
影响因子：
2.7
通讯作者：
Serra, Rosa
中科院分区：
文献类型：
--
作者：
Wang, Ying;Cox, Megan K.;Coricor, George;MacDougall, Mary;Serra, Rosa
由于在许多信号传导缺陷小鼠模型中的围产期致死性，很难检查TGF-β 1在出生后牙齿发育中的作用。为了解决Tgfbr 2在出生后牙齿发育中的作用，我们产生了一只小鼠，其中Tgfbr 2在成牙本质细胞和骨生成间充质中被删除。生成Osx-Cre; Tgfbr 2fl/fl小鼠（Tgfbr 2cko），并比较Tgfbr 2cko和对照同窝仔的出生后牙齿发育。X线和μCT分析显示，Tgfbr 2cko小鼠磨牙根端牙本质基质密度降低。突变小鼠磨牙形态异常，磨牙萌出延迟。最重要的是，出生后第10天观察到牙根形成缺陷，包括牙根伸长失败。角蛋白-14（K14）的免疫染色用于描绘Hertwig上皮根鞘（HERS）。结果显示Tgfbr 2cko小鼠中HERS的延长和解体延迟。此外，HERS得以维持，并且分解成上皮残余物被减弱，这表明Tgfbr 2作用于牙间充质以间接调节HERS的形成和维持。成牙本质细胞组织的改变和Dspp表达的减少表明突变小鼠中成牙本质细胞分化被破坏，可能导致牙根形成缺陷。然而，表达的Nfic，根发育的关键间充质调节，是相似的Tgfbr 2cko小鼠和对照组。牙齿周围骨中破骨细胞的数量减少，成骨细胞分化被破坏，可能导致牙根和萌出缺陷。我们的结论是，TGFBR 2在牙齿间充质和骨是牙齿发育所需的，特别是根的形成。
It has been difficult to examine the role of TGF-ß in post-natal tooth development due to perinatal lethality in many of the signaling deficient mouse models. To address the role of Tgfbr2 in postnatal tooth development, we generated a mouse in which Tgfbr2 was deleted in odontoblast-and bone-producing mesenchyme. Osx-Cre;Tgfbr2fl/fl mice were generated (Tgfbr2cko) and postnatal tooth development was compared in Tgfbr2cko and control littermates. X-ray and μCT analysis showed that in Tgfbr2cko mice radicular dentin matrix density was reduced in the molars. Molar shape was abnormal and molar eruption was delayed in the mutant mice. Most significantly, defects in root formation, including failure of the root to elongate, were observed by postnatal day 10. Immunostaining for Keratin-14 (K14) was used to delineate Hertwig's epithelial root sheath (HERS). The results showed a delay in elongation and disorganization of the HERS in Tgfbr2cko mice. In addition, the HERS was maintained and the break up into epithelial rests was attenuated suggesting that Tgfbr2 acts on dental mesenchyme to indirectly regulate the formation and maintenance of the HERS. Altered odontoblast organization and reduced Dspp expression indicated that odontoblast differentiation was disrupted in the mutant mice likely contributing to the defect in root formation. Nevertheless, expression of Nfic, a key mesenchymal regulator of root development, was similar in Tgfbr2cko mice and controls. The number of osteoclasts in the bone surrounding the tooth was reduced and osteoblast differentiation was disrupted likely contributing to both root and eruption defects. We conclude that Tgfbr2 in dental mesenchyme and bone is required for tooth development particularly root formation.
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影响因子：
1.5
作者：
Chytil, A;Magnuson, MA;Moses, HL
通讯作者：
Moses, HL
影响因子：
2.7
作者：
Berdal, A.;Castaneda, B.;Lezot, F.
通讯作者：
Lezot, F.
DOI：
10.1359/jbmr.091103
发表时间：
2010-05
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：
Huang X;Xu X;Bringas P Jr;Hung YP;Chai Y
通讯作者：
Chai Y
影响因子：
3
作者：
Arvidsson S;Kwasniewski M;Riaño-Pachón DM;Mueller-Roeber B
通讯作者：
Mueller-Roeber B
影响因子：
4.6
作者：
Ito, Y;Yeo, JY;Chai, Y
通讯作者：
Chai, Y