title: Lipopolysaccharide induces the migration of human dental pulp cells by up-regulating miR-146a.
abstract: BACKGROUND
  MicroRNAs are small noncoding RNAs that play crucial roles in regulating normal and pathologic functions. Bacterial lipopolysaccharide (LPS) is one of the key regulators of pulpal pathogenesis. This study investigated how LPS regulates microRNA expression and affects the phenotype of human dental pulp cells (DPCs).
  
  
  METHODS
  Primary DPCs were established and immortalized to achieve immortalized DPCs (I-DPCs). DPCs and I-DPCs were treated with LPS and examined to identify changes in microRNA expression, cell proliferation, and cell migration. Quantitative reverse-transcriptase polymerase chain reaction was used to detect changes in gene expression. Exogenous miR-146a expression was performed transfection with pre-mir-146a mimic. Knockdown of interleukin receptor-associated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) expression was performed by small interference oligonucleotide transfection. Western blot analysis was used to detect changes in the expression of the IRAK1 and TRAF6 proteins.
  
  
  RESULTS
  The differentiation of DPCs was induced by osteogenic medium. I-DPCs had a higher level of human telomerase reverse transcriptase gene than the parental DPCs. Up-regulation of miR-146a expression and an increase in migration was induced by LPS treatment of DPCs and I-DPCs. Exogenous miR-146a expression increased the migration of DPCs and I-DPCs and down-regulated the expression of IRAK1 and TRAF6. Knockdown of IRAK1 and/or TRAF6 increased the migration of DPCs.
  
  
  CONCLUSIONS
  The results suggested that LPS is able to increase the migration of DPCs by modulating the miR-146a-TRAF6/IRAK1 regulatory cascade.
authors.affiliation: Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Min-Ching
authors.initials: MC
authors.lastname: Wang
authors.forename: Pei-Shih
authors.initials: PS
authors.lastname: Hung
authors.forename: Hsi-Feng
authors.initials: HF
authors.lastname: Tu
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Shih
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Li
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Chang
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003470:Culture Media; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000032:analysis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D035683:MicroRNAs / Q000187:drug effects* / Q000235:genetics; D010012:Osteogenesis / Q000502:physiology; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048029:TNF Receptor-Associated Factor 6 / Q000032:analysis / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D003470:Culture Media; D008070:Lipopolysaccharides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D048029:TNF Receptor-Associated Factor 6; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases