title: The microRNA 132 regulates fluid shear stress-induced differentiation in periodontal ligament cells through mTOR signaling pathway.
abstract: OBJECTIVE
  Once tissue destruction has occurred, the differentiation of periodontal ligament (PDL) cells into osteoblasts plays an important role in repairing the oral cavity.
  
  
  METHODS
  In this work, we measured the proliferation and differentiation of PDL cells after fluid shear stress (FSS) treatment by ALP activity assays and in vitro mineralization assays respectively. The levels of miRNA in PDL cells treated with FSS or not were detected by using microRNA arrays. The possible signaling pathway was determined by western-blot.
  
  
  RESULTS
  This study demonstrates that FSS modulates several functions of human PDL cells. Specifically, increasing FSS in fixed increments regulates the proliferation and differentiation of PDL cells. Through microRNA arrays, we find that FSS induced-differentiation is accompanied by a significantly higher level of miR-132 compared to untreated controls. Phosphorylated levels of the P13K, AKT, mTOR, and p70S6K proteins also significantly increases in FSS-treated PDL cells. Finally, the FSS-induced differentiation of PDL cells is inhibited by miR-132 knockdown probe and the mTOR signaling pathway inhibitor BEZ235.
  
  
  CONCLUSIONS
  Our data support the hypothesis that FSS-induced differentiation and proliferation involves the PI3K/AKT/mTOR signaling axis, through a process involving mir-132.
authors.affiliation: Department of Orthodontics, School of Stomatology, China Medical University; Shenyang City, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D033081:Shear Strength; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011804:Quinolines; D058570:TOR Serine-Threonine Kinases; C547077:MIRN132 microRNA, human; C546842:MTOR protein, human; C531198:dactolisib