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
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, 14#, 3rd section of Renmin South Road, Chengdu 610041, PR China.
Department of Biomedical Sciences, Baylor College of Dentistry, TX A&M University, 3302 Gaston Ave, Dallas, TX 75246, USA.
Exp Cell Res. 2017 Apr 15;353(2):55-62. doi: 10.1016/j.yexcr.2016.12.026. Epub 2017 Feb 20.
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.
肌成纤维细胞是在结缔组织重塑和重建中起关键作用的特殊细胞。α-平滑肌肌动蛋白（α-SMA）、波形蛋白和腱生蛋白-C是肌成纤维细胞表型，而α-SMA是表型标志物。人类牙周膜细胞（hPDLCs）在正畸力作用下分化为肌成纤维细胞这一观察结果，为理解正畸牙齿移动所涉及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）中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，我们发现与未加载对照相比，正畸加载下PDL的张力和压缩区域中Wnt3α、转化生长因子-β1（TGF-β1）、α-SMA和腱生蛋白-C的表达均增加，这表明上调的Wnt3α和TGF-β1信号可能在正畸力作用下的肌成纤维细胞分化中发挥作用。我们在体外揭示Wnt3α和TGF-β1均促进hPDLCs向肌成纤维细胞分化。Dickkopf-1（DKK1）以β-连环蛋白依赖的方式损害Wnt3α诱导的肌成纤维细胞分化。TGF-β1通过JNK依赖的机制刺激肌成纤维细胞分化。DKK1对TGF-β1诱导的肌成纤维细胞表型无显著影响。
