title: Wnt3α and transforming growth factor-β induce myofibroblast differentiation from periodontal ligament cells via different pathways.
abstract: 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.
authors.affiliation: 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. Electronic address: zybbda@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: 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. Electronic address: taopaojun83@126.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Biomedical Sciences, Baylor College of Dentistry, TX A&M University, 3302 Gaston Ave, Dallas, TX 75246, USA. Electronic address: jfeng@bcd.tamhsc.edu.
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
authors.affiliation: 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. Electronic address: weis2004@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, 14#, 3rd section of Renmin South Road, Chengdu 610041, PR China. Electronic address: guevaralz@163.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 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. Electronic address: 526982847@qq.com.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Li
authors.affiliation: 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. Electronic address: nancyyaya@foxmail.com.
authors.forename: Yating
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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. Electronic address: youngf15@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 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. Electronic address: huanzenghxkq@163.com.
authors.forename: Huan
authors.initials: H
authors.lastname: Zeng
authors.affiliation: 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. Electronic address: 593752840@qq.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: 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. Electronic address: Xiang_zichao@126.com.
authors.forename: Zichao
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: 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. Electronic address: 731915807@qq.com.
authors.forename: Chaoran
authors.initials: C
authors.lastname: Xue
authors.affiliation: 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. Electronic address: baiding@scu.edu.cn.
authors.forename: Ding
authors.initials: D
authors.lastname: Bai
authors.affiliation: 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. Electronic address: xhan@scu.edu.cn.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Han
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism; D010513:Periodontal Ligament / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D019063:Tenascin / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics; D060509:Wnt3A Protein / Q000096:biosynthesis* / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D019063:Tenascin; D016212:Transforming Growth Factor beta; D014746:Vimentin; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin
keywords: Dickkopf-1; Myofibroblast; Transforming growth factor-β; Wnt3α; α-smooth muscle actin