title: TNF-alpha stimulation increases dental pulp stem cell migration in vitro through integrin alpha-6 subunit upregulation.
abstract: OBJECTIVE
  The dissemination of stem cells into tissues requiring inflammatory and reparative response is fundamentally dependent upon their chemotactic migration. Expression of TNF-α is up regulated in inflamed pulps. Dental pulp cells are also known to express integrin α6 subunit. Expression of integrin subunit α6 has been linked to the acquisition of migratory potential in a wide variety of cell types in both pathological and physiological capacities. Therefore, in this study we examined the effects of a pleiotropic cytokine TNF-α on the migration of hDPSCs and investigated its relationship with expression of integrin α6 in hDPSCs during chemotactic migration.
  
  
  METHODS
  hDPSC cultures were established. Protein expression profile of α6 integrin subunit was determined. Effect of exogenous TNF-α (50ng/mL) on hDPSCs' migration potential was evaluated by transwell inserts and in vitro scratch assay. Upregulation/downregulation of TNF-α mediated migration was assayed in presence/absence of integrin α6 respectively. To suppress integrin α6 expression, cells were transfected with integrin α6 siRNA and then cell migration and cytoskeletal changes were evaluated.
  
  
  RESULTS
  Our results showed significant increase of hDPSCs' migration after stimulation with TNF-α. By knockdown of integrin α6, which is upregulated by TNF-α, we observed a decrease in the TNF-α directed chemotaxis of hDPSCs.
  
  
  CONCLUSIONS
  In this study, we show that activation of integrin α6 brought about by TNF-α led to an increase in migratory activity in DPSCs in vitro thus describing a novel association between a cytokine TNF-α and α6 chain of an adhesion receptor integrin in regulating migration of hDPSCs.
authors.affiliation: Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China; Oral Biomedical Research Institute of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China. Electronic address: mollyzrx@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China. Electronic address: fushanqi@sina.cn.
authors.forename: Shanqi
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China. Electronic address: sidra.raf@gmail.com.
authors.forename: Sidra
authors.initials: S
authors.lastname: Fahim
authors.affiliation: Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China; Oral Biomedical Research Institute of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China. Electronic address: panshuang79@163.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China. Electronic address: helina426@163.com.
authors.forename: He
authors.initials: H
authors.lastname: Lina
authors.affiliation: Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China. Electronic address: 1534085074@qq.com.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China; Oral Biomedical Research Institute of Harbin Medical University, 143 Yiman Street, Nangang District, Harbin, 150001, China. Electronic address: yumeiniu@163.com.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Niu
mesh_terms: D000328:Adult; D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D008964:Molar, Third; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D016207:Cytokines; D039503:Integrin alpha6; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha
keywords: Cytokine; Dental pulp stem cell; Integrin α6; Migration; Regeneration; TNF-α