title: SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways.
abstract: SDF-1 (stromal cell derived factor-1) has been found to be widely expressed during dental pulp inflammation, while hDPSCs (human dental pulp stem cells) contribute to the repair of dental pulp. We showed that the migration of hDPSCs was induced by SDF-1 in a concentration-dependent manner and could be inhibited with siCXCR4 (C-X-C chemokine receptor type 4) and siCDC42 (cell division control protein 42), as well as drug inhibitors such as AMD3100 (antagonist of CXCR4), LY294002 (inhibitor of PI3K) and PF573228 (inhibitor of FAK). It was also confirmed that SDF-1 regulated the phosphorylation of FAK (focal adhesion kinases) on cell membranes and the translocation of β-catenin into the cell nucleus. Subsequent experiments confirmed that the expression of CXCR4 and β-catenin and the phosphorylation of FAK, PI3K (phosphoinositide 3-kinase), Akt and GSK3β (glycogen synthase kinase-3β) were altered significantly with SDF-1 stimulation. FAK and PI3K worked in coordination during this process. Our findings provide direct evidence that SDF-1/CXCR4 axis induces hDPSCs migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways, implicating a novel mechanism of dental pulp repair and a possible application of SDF-1 for the treatment of pulpitis.
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.|Translational Research Team, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.|Translational Research Team, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Stomatology, Medical Plastic and Aesthetic Center, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.|Translational Research Team, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.|Translational Research Team, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.|Translational Research Team, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D051176:beta Catenin; D058539:Phosphatidylinositol 3-Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt