title: Fluid shear stress regulates metalloproteinase-1 and 2 in human periodontal ligament cells: involvement of extracellular signal-regulated kinase (ERK) and P38 signaling pathways.
abstract: Matrix metalloproteinase (MMP)-1, 2, with their endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1, 2 are critical for extracellular matrix remodeling in human periodontal ligament (PDL) and their expression are sensitive to mechanical stresses. Shear stress as the main type of mechanical stress in tooth movement is involved in matrix turnover. However, how shear stress regulates MMPs and TIMPs system is still unclear. In this study, we investigated the effect of fluid shear stress on expression of MMP-1, 2 and TIMP-1, 2 in human PDL cells and the possible roles of mitogen-activated protein kinases in this process. Three levels of fluid shear stresses (6, 9 and 12 dyn/cm(2)) were loaded on PDL cells for 2, 4, 8 and 12h. The results indicated that fluid shear stress rearranged cytoskeleton in PDL cells. Fluid shear stress increased expression of MMP-1, 2, TIMP-1 and suppressed TIMP-2 expression. MAP kinases including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 were activated rapidly by fluid shear stress. The ERK inhibitor blocked fluid shear stress induced MMP-1 expression and P38 inhibitor reduced fluid shear stress stimulated MMP-2 expression. Our study suggested that fluid shear stress involved in PDL remodeling via regulating MMP-1, 2 and TIMP-1, 2 expression. ERK regulated fluid shear stress induced MMP-1 expression and P38 play a role in fluid shear stress induced MMP-2 upregulation.
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Xianghui
authors.initials: X
authors.lastname: Gong
authors.forename: Meili
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Jia
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.forename: Luoping
authors.initials: L
authors.lastname: Chen
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D010513:Periodontal Ligament / Q000166:cytology / Q000201:enzymology*; D033081:Shear Strength / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D014087:Tooth Movement Techniques; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
chemical_list: C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D048051:p38 Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1