title: Fluid shear stress stimulates osteogenic differentiation of human periodontal ligament cells via the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase signaling pathways.
abstract: BACKGROUND
  Fluid shear stress (FSS) is a major type of mechanical stress that is loaded on human periodontal ligament cells (hPDLCs) during mastication and orthodontic tooth movement. This study aims to clarify the effect of FSS on the osteogenic differentiation of hPDLCs and to further verify the involvement of mitogen-activated protein kinase (MAPK) signaling in this process.
  
  
  METHODS
  After isolation and characterization, hPDLCs were subjected to 2-hour FSS at 12 dynes/cm(2), and cell viability, osteogenic gene mRNA expression, alkaline phosphatase (ALP) activity, secretion of Type I collagen (COL-I), and calcium deposition were assayed. The levels of phosphorylated p38 and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) in response to FSS were detected by Western blot, and the involvement of ERK1/2 and p38 MAPK signaling pathways in hPDLC osteogenesis under FSS was investigated using the specific MAPK inhibitors U0126 (2Z,3Z)-2,3-bis[amino(2-aminophenylthio)methylene]succinonitrile,ethanol) and SB203580 (4-[4-(4-fluorophenyl)-2-(4-[methylsulfinyl]phenyl)-1H-imidazol-5-yl]pyridine).
  
  
  RESULTS
  The application of FSS on hPDLCs induced an early morphologic change and rearrangement of filamentous actin. ALP activity, messenger RNA (mRNA) levels of osteogenic genes, COL-I, and osteoid nodules were significantly increased by FSS. Moreover, ERK1/2 and p38 were activated in different ways after FSS exposure. U0126 and SB203580 completely blocked the FSS-induced increases in ALP activity and osteogenic gene mRNA expression and osteoid nodules formation.
  
  
  CONCLUSIONS
  FSS is an effective approach for stimulating osteogenic differentiation of hPDLCs. The ERK1/2 and p38 MAPK signaling pathways are involved in this cellular process.
authors.affiliation: Department of Stomatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Zhuli
authors.initials: Z
authors.lastname: Peng
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Mai
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Qin
authors.initials: Q
authors.lastname: Mao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Limin
authors.initials: L
authors.lastname: Liu
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Ai
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D001696:Biomechanical Phenomena; D002070:Butadienes / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D048430:Cell Shape; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D024042:Collagen Type I / Q000032:analysis; D005260:Female; D006801:Humans; D057446:Hydrodynamics; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D010513:Periodontal Ligament / Q000166:cytology* / Q000201:enzymology; D011725:Pyridines / Q000494:pharmacology; D013314:Stress, Mechanical; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000502:physiology*
chemical_list: D002070:Butadienes; D024042:Collagen Type I; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; C113580:U 0126; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase; C093642:SB 203580; D002118:Calcium
keywords: Cell differentiation; p38 mitogen-activated protein kinases; periodontal ligament; stress, mechanical