Enhanced Activation of Canonical Wnt Signaling Confers Mesoderm-Derived Parietal Bone with Similar Osteogenic and Skeletal Healing Capacity to Neural Crest-Derived Frontal Bone.
Enhanced Activation of Canonical Wnt Signaling Confers Mesoderm-Derived Parietal Bone with Similar Osteogenic and Skeletal Healing Capacity to Neural Crest-Derived Frontal Bone.
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DOI：
10.1371/journal.pone.0138059
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Longaker MT
中科院分区：
文献类型：
--
作者：
Li S;Quarto N;Senarath-Yapa K;Grey N;Bai X;Longaker MT
骨形成和骨骼修复是一个动态的过程，涉及成骨细胞增殖和分化之间的微调平衡，由多个信号通路编排。已知典型Wnt（cWnt）信号传导在这些过程中起关键作用。在目前的研究中，我们使用了一个转基因小鼠模型，靶向破坏axin 2，cWnt信号的负调节，我们研究了增强激活cWnt信号对成骨能力和骨骼修复的影响。具体来说，我们研究了两种不同胚胎组织来源的颅骨：神经嵴来源的额骨和中胚层来源的顶骨，我们研究了额骨和顶骨以及衍生成骨细胞的增殖和凋亡活性。我们发现Axin 2-/-和野生型颅骨之间的细胞增殖和凋亡活性存在显著差异，Axin 2-/-显示出增殖活性增加和凋亡水平降低。此外，我们比较了Axin 2-/-和野生型神经嵴来源的额骨和中胚层来源的顶骨中的成骨细胞分化和骨再生。我们的研究结果表明，与野生型相比，Axin 2-/-小鼠的成骨细胞分化或骨再生显著增加，Axin 2-/-顶骨和衍生的成骨细胞显示出“神经嵴衍生的额骨样”特征，其典型特征是比顶骨具有更高的成骨能力和骨骼修复。综上所述，我们的结果强烈表明，cWnt信号传导的增强的激活增加了中胚层起源的颅骨骨（例如顶骨）的骨骼电位，其程度类似于神经嵴起源骨（例如额骨）的骨骼电位。因此，为cWnt信号传导在骨生成和骨再生中发挥的核心作用提供了进一步的证据。
Bone formation and skeletal repair are dynamic processes involving a fine-tuned balance between osteoblast proliferation and differentiation orchestrated by multiple signaling pathways. Canonical Wnt (cWnt) signaling is known to playing a key role in these processes. In the current study, using a transgenic mouse model with targeted disruption of axin2, a negative regulator of cWnt signaling, we investigated the impact of enhanced activation of cWnt signaling on the osteogenic capacity and skeletal repair. Specifically, we looked at two calvarial bones of different embryonic tissue origin: the neural crest-derived frontal bone and the mesoderm-derived parietal bone, and we investigated the proliferation and apoptotic activity of frontal and parietal bones and derived osteoblasts. We found dramatic differences in cell proliferation and apoptotic activity between Axin2 -/- and wild type calvarial bones, with Axin2 -/- showing increased proliferative activity and reduced levels of apoptosis. Furthermore, we compared osteoblast differentiation and bone regeneration in Axin2 -/- and wild type neural crest-derived frontal and mesoderm-derived parietal bones, respectively. Our results demonstrate a significant increase either in osteoblast differentiation or bone regeneration in Axin2 -/- mice as compared to wild type, with Axin2 -/- parietal bone and derived osteoblasts displaying a “neural crest-derived frontal bone-like” profile, which is typically characterized by higher osteogenic capacity and skeletal repair than parietal bone. Taken together, our results strongly suggest that enhanced activation of cWnt signaling increases the skeletal potential of a calvarial bone of mesoderm origin, such as the parietial bone to a degree similar to that of a neural crest origin bone, like the frontal bone. Thus, providing further evidence for the central role played by the cWnt signaling in osteogenesis and skeletal-bone regeneration.