title: MMP-7 and TIMP-1, new targets in predicting poor wound healing in apical periodontitis.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) are strongly associated with tissue destruction because of inflammation. In this study, we investigated the expression of MMPs and TIMPs messenger RNA and protein levels in apical periodontitis lesions.
  
  
  METHODS
  Tissue samples from patients presenting clinical signs of chronic apical abscess (CAA) or asymptomatic apical periodontitis (AAP) were collected postoperatively and used for gene expression analysis of MMP-2, -3, -7, -9, -14, -16, and -25; TIMP-1; and TIMP-2 in real-time polymerase chain reaction. Immunohistochemistry was also performed to detect the expression of MMP-7 and TIMP-1 proteins. Lastly, U-937 cells were induced to terminal differentiation into macrophages, infected with purified Escherichia coli lipopolysaccharide, and assessed for the expression of MMP-7 and TIMP-1 using immunocytochemistry and confocal microscopy.
  
  
  RESULTS
  Significantly higher messenger RNA levels were found for all genes in AAP and CAA samples when compared with healthy control samples (P < .001). AAP cases exhibited significantly higher TIMP-1 when compared with CAA cases, whereas CAA cases showed higher MMP-2, MMP-7, and MMP-9 messenger RNA levels (P < .05). We also detected positive the expression of MMP-7 and TIMP-1 proteins in the tissue samples. The expression of both MMP-7 and TIMP-1 were increased in lipopolysaccharide-stimulated cells compared with nonstimulated cells and appear to colocalize in the Golgi apparatus.
  
  
  CONCLUSIONS
  MMPs appear to have an influential role in CAA cases in which ongoing tissue destruction is observed. TIMPs are preferentially associated with AAP, perhaps as a subsequent defense mechanism against excessive destruction. Taken together, our findings implicate MMP and TIMP molecules in the dynamics of inflammatory periapical lesion development.
authors: Department of Endodontics, University of Texas School of Dentistry at Houston, Houston, Texas 77054, USA.
authors: Ariadne
authors: A
authors: Letra
authors: Ghazaleh
authors: G
authors: Ghaneh
authors: Min
authors: M
authors: Zhao
authors: Herbert
authors: H
authors: Ray
authors: Carolina Favaro
authors: CF
authors: Francisconi
authors: Gustavo Pompermaier
authors: GP
authors: Garlet
authors: Renato Menezes
authors: RM
authors: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D058070:Asymptomatic Diseases; D018929:Cell Culture Techniques; D004926:Escherichia coli / Q000502:physiology; D058851:GPI-Linked Proteins / Q000032:analysis; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D053511:Matrix Metalloproteinase 14 / Q000032:analysis; D053513:Matrix Metalloproteinase 16 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020783:Matrix Metalloproteinase 7 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000032:analysis; D008875:Middle Aged; D010482:Periapical Abscess / Q000201:enzymology; D010485:Periapical Periodontitis / Q000201:enzymology*; D011480:Protease Inhibitors / Q000032:analysis*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D020298:U937 Cells; D014945:Wound Healing / Q000502:physiology; D055815:Young Adult
chemical_list: D058851:GPI-Linked Proteins; D008070:Lipopolysaccharides; C507102:MMP16 protein, human; D011480:Protease Inhibitors; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D053513:Matrix Metalloproteinase 16; D053504:Matrix Metalloproteinases, Membrane-Associated; C403928:matrix metalloproteinase 25; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: Apical periodontitis; gene expression; matrix metalloproteinase; tissue inhibitor of metalloproteinase