Wnt signaling regulates pulp volume and dentin thickness.
Wnt signaling regulates pulp volume and dentin thickness.
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DOI：
10.1002/jbmr.2088
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发表时间：
2014-04
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影响因子：
--
通讯作者：
Helms JA
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文献类型：
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作者：
Lim WH;Liu B;Cheng D;Hunter DJ;Zhong Z;Ramos DM;Williams BO;Sharpe PT;Bardet C;Mah SJ;Helms JA
成牙本质细胞、成牙骨质细胞、成釉细胞和成骨细胞都在颅面复合体中形成矿化组织，并且所有这些细胞类型在出生后的生活中都表现出活跃的Wnt信号传导。我们开始了解这种Wnt信号传导的功能，通过评估小鼠的表型，其中基本的Wnt伴侣蛋白，无翼被消除。Wls的缺失仅限于表达骨钙素的细胞，其除了成骨细胞之外还包括成牙本质细胞、成牙骨质细胞和成釉细胞。牙本质、牙骨质、釉质和骨都在OCN-Cre;Wlsfl/fl小鼠中形成，但它们的体内平衡受到显著影响。最显著的特征是牙本质体积和密度显著增加。我们将这种牙本质体积的增加归因于Wnt介导的Runx 2的错误调节。正常情况下，Wnt信号刺激Runx 2，继而抑制DSP;这种抑制必须被解除，成牙本质细胞才能分化。在OCN-Cre;Wlsfl/fl小鼠中，Wnt途径活化减少，Runx 2水平下降。Runx 2介导的DSP抑制被解除，成牙本质细胞分化相应地增强。这项研究表明Wnt信号在颅面复合体矿化组织的稳态中的重要性。
Odontoblasts, cementoblasts, ameloblasts and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wingless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin, which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN-Cre;Wlsfl/fl mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt-mediated mis-regulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits DSP; this inhibition must be relieved for odontoblasts to differentiate. In OCN-Cre;Wlsfl/fl mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2-mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex.