Absence of endochondral ossification and craniosynostosis in posterior frontal cranial sutures of Axin2(-/-) mice.
Absence of endochondral ossification and craniosynostosis in posterior frontal cranial sutures of Axin2(-/-) mice.
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DOI：
10.1371/journal.pone.0070240
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Quarto N
中科院分区：
文献类型：
--
作者：
Behr B;Longaker MT;Quarto N
在出生后的第一个月，小鼠颅穹窿的后额缝（PF）通过软骨内骨化闭合，而其他缝保持开放。这些过程受到经典Wnt信号的严格调控。低水平的活性经典Wnt信号传导使软骨内骨化和PF缝合闭合成为可能，而经典Wnt的组成性激活导致PF缝合通畅。因此，我们试图用基因敲除小鼠模型来测试这一概念。Axin 2 −/−小鼠的PF缝线类似于一种持续激活的经典Wnt信号传导状态，在PF缝线闭合的生理时间过程中进行了研究，并与野生型同窝仔进行了详细比较。组织学分析显示，与野生型相比，Axin 2 −/− PF缝线的结构发生了显著改变。颅内层之间的距离显著增加，缝合闭合明显延迟。此外，没有发生生理性软骨内骨化，而是在P7时在颅内外骨层之间出现异位软骨，并最终在P13时内卷。定量PCR分析显示Axin 2 −/− PF缝线中缺乏Col 10 α1上调。免疫组织化学和基因表达分析还显示，与I型胶原蛋白相比，II型胶原蛋白含量较高，并且Axin 2-/-PF缝线的软骨中不存在Mmp-9。此外，TUNEL染色显示，与野生型相比，在P9和P11时Axin 2 −/− PF缝线中凋亡软骨细胞的百分比较高。这些数据表明Axin 2 −/− PF缝线缺乏生理性软骨内骨化，含有异位软骨，并显示缝线闭合延迟。
During the first month of life, the murine posterior-frontal suture (PF) of the cranial vault closes through endochondral ossification, while other sutures remain patent. These processes are tightly regulated by canonical Wnt signaling. Low levels of active canonical Wnt signaling enable endochondral ossification and therefore PF-suture closure, whereas constitutive activation of canonical Wnt causes PF-suture patency. We therefore sought to test this concept with a knockout mouse model. PF-sutures of Axin2−/− mice, which resemble a state of constantly activated canonical Wnt signaling, were investigated during the physiological time course of PF-suture closure and compared in detail with wild type littermates. Histological analysis revealed that the architecture in Axin2−/− PF-sutures was significantly altered in comparison to wild type. The distance between the endocranial layers was dramatically increased and suture closure was significantly delayed. Moreover, physiological endochondral ossification did not occur, rather an ectopic cartilage appeared between the endocranial and ectocranial bone layers at P7 which eventually involutes at P13. Quantitative PCR analysis showed the lack of Col10α1 upregulation in Axin2−/− PF-suture. Immunohistochemistry and gene expression analysis also revealed high levels of type II collagen as compared to type I collagen and absence of Mmp-9 in the cartilage of Axin2−/− PF-suture. Moreover, TUNEL staining showed a high percentage of apoptotic chondrocytes in Axin2−/− PF-sutures at P9 and P11 as compared to wild type. These data indicated that Axin2−/− PF-sutures lack physiological endochondral ossification, contain ectopic cartilage and display delayed suture closure.
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影响因子：
3.7
作者：
Slater, Bethany J.;Liu, Karen J.;Kwan, Matthew D.;Quarto, Natalina;Longaker, Michael T.
通讯作者：
Longaker, Michael T.
影响因子：
5.3
作者：
Lefebvre, V;Huang, WD;deCrombrugghe, B
通讯作者：
deCrombrugghe, B
DOI：
10.1073/pnas.0504750102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
4.6
作者：
Yu, HMI;Jerchow, B;Hsu, W
通讯作者：
Hsu, W
DOI：
10.1073/pnas.1631288100
发表时间：
2003-08-05
影响因子：
11.1
作者：
Mori-Akiyama, Y;Akiyama, H;de Crombrugghe, B
通讯作者：
de Crombrugghe, B