Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells

Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells
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Wnt10a 的下调影响间充质细胞的牙发生和增殖

DOI:
10.1016/j.bbrc.2013.03.088
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发表时间:
2013-05-17
影响因子:
3.1
通讯作者:
Feng, Hailan
Feng, Hailan
中科院分区:
生物学4区
文献类型:
--
作者:
Liu, Yang;Han, Dong;Feng, Hailan

文献摘要

被引文献

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在牙齿发育异常的患者中发现了WNT10a突变。在小鼠中,在牙胚中发现了Wnt10a的表达,但其作用尚未阐明。我们的目的是研究Wnt10a在牙形成中的作用。分离钟形期下颌第一磨牙胚间充质细胞,转染Wnt10a SiRNA或质粒,与磨牙胚上皮部分重新结合。对照组采用重组SiRNA或空载体。将重组的牙胚移植到小鼠肾下囊内。基因修饰后,检测体外培养牙间充质细胞的增殖情况和Dspp的表达。对照组的12个重新关联的牙胚全部恢复成牙,而敲低Wnt10a组的12个牙胚中只有5个发育成牙。Wnt10a基因敲除后,体外培养的间充质细胞增殖受到抑制。Wnt10a敲低和过表达导致Dspp下调和上调。我们得出结论,下调Wnt10n会损害牙形成和细胞增殖,而Wnt10a会调节间充质细胞中Dspp的表达。这些发现有助于阐明WNT10A突变患者牙齿发育异常的机制。(c) 2013爱思唯尔公司版权所有。
The WNT10a mutation has been found in patients with abnormal odontogenesis. In mice, Wnt10a expression is found in the tooth germ, but its role has not yet been elucidated. We aimed to investigate the role of Wnt10a in odontogenesis. Mesenchymal cells of the first mandibular molar germ at the bell stage were isolated, transfected with Wnt10a SiRNA or plasmid, and reassociated with epithelial part of the molar germ. Scrambled SiRNA or empty vector was used in the control group. The reassociated tooth germs were transplanted into mice subrenal capsules. After gene modification, dental mesenchymal cells cultured in vitro were checked for cell proliferation and the expression of Dspp was examined. All 12 reassociated tooth germs in the control group resumed odontogenesis, while only 5 of 12 in the Wnt10a knockdown group developed into teeth. After Wnt10a knockdown, the mesenchymal cells cultured in vitro presented repressed proliferation. Wnt10a knockdown and overexpression led to both down- and up-regulation of Dspp. We conclude that the down-regulation of Wnt10n impairs odontogensis and cell proliferation, and that Wnt10a regulates Dspp expression in mesenchymal cells. These findings help to elucidate the mechanism of abnormal tooth development in patients with the WNT10A mutation. (c) 2013 Elsevier Inc. All rights reserved.