FGF8 Signaling Alters the Osteogenic Cell Fate in the Hard Palate
FGF8 Signaling Alters the Osteogenic Cell Fate in the Hard Palate
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FGF8 信号传导改变硬腭中的成骨细胞命运
DOI：
10.1177/0022034517750141
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发表时间：
2018-01
影响因子：
7.6
通讯作者：
YiPing Chen
中科院分区：
文献类型：
--
作者：
Jue Xu;Zhen Huang;Weiqi Wang;Xiaoqian Tan;Hua Li;Y;ing Zhang;Weidong Tian;Tao Hu;YiPing Chen
成纤维细胞生长因子（FGF）信号转导已涉及膜内和软骨内骨化中的成骨调节。在发育中的腭，前骨腭形成颅神经嵴（CNC）衍生的间充质细胞的直接分化，但在发育中的腭调控成骨细胞的命运的信号仍然不清楚。在本研究中，我们研究了FGF信号在腭间充质细胞成骨命运决定中的潜在作用。我们发现，使用Shox2Cre敲入等位基因和R26RFgf8等位基因在前腭中局部激活FGF8信号传导导致独特的腭缺陷：上颌骨的腭突完全丧失以及前腭中异位软骨组织的形成。这种异常的发育过程伴随着显著升高的细胞增殖水平，这导致异常增厚的腭组织，其中上颌骨的腭突通常会形成，并通过Osterix表达的完全抑制，这是骨形成缺乏的原因。Runx2最初与Sox 9共表达，随后与Col II共表达，表明异位软骨组织中成骨命运向软骨形成命运的转化。与独特的腭表型一致，RNA测序分析显示，增强的FGF 8信号转导下调了参与骨化、生物矿物组织发育和骨矿化的基因，但上调了参与细胞增殖、软骨发育和细胞命运定型的基因，这进一步得到了所选基因的定量实时逆转录聚合酶链反应验证的支持。我们的研究结果表明，FGF8信号传导作为成骨命运的负调节因子，足以将CNC细胞衍生的间充质细胞的子集转化为前硬腭中的软骨，这将对将来定向分化CNC衍生的前体细胞用于临床应用产生影响。
Fibroblast growth factor (FGF) signaling has been implicated in the regulation of osteogenesis in both intramembranous and endochondral ossifications. In the developing palate, the anterior bony palate forms by direct differentiation of cranial neural crest (CNC)–derived mesenchymal cells, but the signals that regulate the osteogenic cell fate in the developing palate remain unclear. In the present study, we investigated the potential role of FGF signaling in osteogenic fate determination of the palatal mesenchymal cells. We showed that locally activated FGF8 signaling in the anterior palate using a Shox2Cre knock-in allele and an R26RFgf8 allele leads to a unique palatal defect: a complete loss of the palatine process of the maxilla as well as formation of ectopic cartilaginous tissues in the anterior palate. This aberrant developmental process was accompanied by a significantly elevated level of cell proliferation, which contributes to an abnormally thickened palatal tissue, where the palatine process of the maxilla would normally form, and by a complete inhibition of Osterix expression, which accounts for the lack of bone formation. The coexpression of Runx2 initially with Sox9 and subsequently with Col II in the ectopic cartilaginous tissues indicates a conversion of osteogenic fate to a chondrogenic one. Consistent with the unique palatal phenotype, RNA-Sequencing analysis revealed that the augmented FGF8 signaling downregulated genes involved in ossification, biomineral tissue development, and bone mineralization but upregulated genes involved in cell proliferation, cartilage development, and cell fate commitment, which was further supported by quantitative real-time reverse transcription polymerase chain reaction validation of selected genes. Our results demonstrate that FGF8 signaling functions as a negative regulator of osteogenic fate and is sufficient to convert a subset of CNC cell-derived mesenchymal cells into cartilage in the anterior hard palate, which will have implications in future directed differentiation of CNC-derived precursor cells for clinical application.
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影响因子：
4.8
作者：
Valta, MP;Hentunen, T;Härkönen, PL
通讯作者：
Härkönen, PL
DOI：
10.1111/j.1749-6632.1996.tb56255.x
发表时间：
1996-06
影响因子：
5.2
作者：
S. Malcolm;W. Reardon
通讯作者：
S. Malcolm;W. Reardon
影响因子：
11.2
作者：
Jitesh Pratap;M. Galindo;S. Zaidi;Diana Vradii;B. Bhat;John A. Robinson;Je-Yong Choi;T. Komori;J. Stein;J. Lian;G. Stein;A. J. Wijnen
通讯作者：
Jitesh Pratap;M. Galindo;S. Zaidi;Diana Vradii;B. Bhat;John A. Robinson;Je-Yong Choi;T. Komori;J. Stein;J. Lian;G. Stein;A. J. Wijnen
影响因子：
4.6
作者：
Yu, K;Xu, JS;Ornitz, DM
通讯作者：
Ornitz, DM
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B