title: Induction of IL-6 and MMP-8 in human periodontal fibroblasts by static tensile strain.
abstract: OBJECTIVE
  Mechanical loading is a potential activator of inflammation and able to stimulate factors for periodontal and alveolar bone destruction. Aim of this study was to investigate the inflammatory response and synthesis of proteinases by human periodontal ligament fibroblast (HPdLF) dependent on different strengths of static tensile strain (STS).
  
  
  METHODS
  HPdLFs were loaded with different STS strengths (1, 5, and 10 %) in vitro. Gene expressions of cyclooxygenase (COX)-2 and interleukin (IL)-6 were analyzed by quantitative real-time polymerase chain reaction. Production of IL-6, prostaglandin E2 (PGE2), matrix metalloproteinase (MMP)-8, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were measured by enzyme-linked immunosorbent assay. Receptor activator of nuclear factor-kappa ligand (RANKL) synthesis was detected by immunocytochemical staining.
  
  
  RESULTS
  Ten percent STS led to an increased gene expression of IL-6 and COX-2 (34.4-fold) in HPdLF, and 1 and 5 % STS slightly reduced the gene expression of IL-6. Synthesis of IL-6 was significantly reduced by 1 % STS and stimulated by 10 % STS. Ten percent STS significantly induced PGE2 production. RANKL was not detectable at any strength of STS. MMP-8 synthesis showed significantly higher values only at 10 % STS, but TIMP-1 was stimulated by 5 and 10 % STS, resulting into highest TIMP-1/MMP-8 ratio at 5 % STS.
  
  
  CONCLUSIONS
  High-strength STS is a potent inducer of periodontal inflammation and MMP-8, whereas low-strength STS shows an anti-inflammatory effect. Moderate-strength STS causes the highest TIMP-1/MMP-8 ratio, leading to appropriate conditions for reformation of the extracellular matrix.
  
  
  CONCLUSIONS
  Furthermore, this study points out that the strength of force plays a pivotal role to achieve orthodontic tooth movement without inducing periodontal inflammation and to activate extracellular matrix regeneration.
authors.affiliation: Department of Orthodontics, University Medical Center, Johannes Gutenberg University Mainz, Augustusplatz 2, 55131, Mainz, Germany, collin.jacobs@unimedizin-mainz.de.
authors.forename: Collin
authors.initials: C
authors.lastname: Jacobs
authors.forename: Christian
authors.initials: C
authors.lastname: Walter
authors.forename: Thomas
authors.initials: T
authors.lastname: Ziebart
authors.forename: Sarah
authors.initials: S
authors.lastname: Grimm
authors.forename: Dan
authors.initials: D
authors.lastname: Meila
authors.forename: Elena
authors.initials: E
authors.lastname: Krieger
authors.forename: Heinrich
authors.initials: H
authors.lastname: Wehrbein
mesh_terms: D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D020784:Matrix Metalloproteinase 8 / Q000096:biosynthesis* / Q000235:genetics; D010519:Periodontium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D053245:RANK Ligand / Q000096:biosynthesis; D013718:Tensile Strength; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D053245:RANK Ligand; D019715:Tissue Inhibitor of Metalloproteinase-1; D020784:Matrix Metalloproteinase 8; D015232:Dinoprostone