Wnt3 alpha and transforming growth factor-beta induce myofibroblast differentiation from periodontal ligament cells via different pathways
Wnt3 alpha and transforming growth factor-beta induce myofibroblast differentiation from periodontal ligament cells via different pathways
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Wnt3 α和转化生长因子-β通过不同途径诱导牙周膜细胞向肌成纤维细胞分化
DOI：
10.1016/j.yexcr.2016.12.026
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发表时间：
2017
影响因子：
3.7
通讯作者：
Han Xianglong
中科院分区：
文献类型：
--
作者：
Xu Hui;He Yao;Feng Jian Q;Shu Rui;Liu Zhe;Li Jingyu;Wang Yating;Xu Yang;Zeng Huan;Xu Xin;Xiang Zichao;Xue Chaoran;Bai Ding;Han Xianglong
肌成纤维细胞是一种特殊的细胞，在结缔组织重塑和重建中起着关键作用。α-平滑肌肌动蛋白(α-SMA)、波形蛋白和肌张力蛋白-C为肌成纤维细胞表型，α-SMA为表型标记物。人牙周膜细胞(HPDLCs)在正畸力作用下分化为肌成纤维细胞，为理解正畸牙移动的生物学和生物力学机制提供了新的视角。然而，导致牙周膜(PDL)肌成纤维细胞分化的细胞特异性分子机制仍不清楚。在本研究中，我们发现WNT3α、转化生长因子-β1(TGFR-β1)、α-SMA和Tenascin-C在正畸载荷作用下的牙周韧带张力区和压力区的表达均增加，提示WNT3α和Tenascin-β1信号的上调可能在正畸力诱导的肌成纤维细胞分化中起作用。我们在体外发现WNT3α和转化生长因子-β1都能促进人PDLCs向肌成纤维细胞分化。Dickkopf-1(DKK1)以α依赖的方式抑制WNT3β诱导的肌成纤维细胞分化。转化生长因子-β-1通过JNK依赖机制促进肌成纤维细胞分化。DKK1对转化生长因子-β-1诱导的肌成纤维细胞表型无明显影响。
Myofibroblasts are specialized cells that play a key role in connective tissue remodeling and reconstruction. Alpha-smooth muscle actin (α-SMA), vimentin and tenascin-C are myofibroblast phenotype, while α-SMA is the phenotypic marker. The observation that human periodontal ligament cells (hPDLCs) differentiate into myofibroblasts under orthodontic force has provided a new perspective for understanding of the biological and biomechanical mechanisms involved in orthodontic tooth movement. However, the cell-specific molecular mechanisms leading to myofibroblast differentiation in the periodontal ligament (PDL) remain unclear. In this study, we found that expression of Wnt3α, transforming growth factor-β1 (TGF-β1), α-SMA and tenascin-C increased in both tension and compression regions of the PDL under orthodontic load compared with unloaded control, suggesting that upregulated Wnt3α and TGF-β1 signaling might have roles in myofibroblast differentiation in response to orthodontic force. We reveal in vitro that both Wnt3α and TGF-β1 promote myofibroblast differentiation from hPDLCs. Dickkopf-1 (DKK1) impairs Wnt3α-induced myofibroblast differentiation in a β-catenin-dependent manner. TGF-β1 stimulates myofibroblast differentiation via a JNK-dependent mechanism. DKK1 has no significant effect on TGF-β1-induced myofibroblastic phenotype.