title: Expression analysis of wound healing genes in human periapical granulomas of progressive and stable nature.
abstract: BACKGROUND
  Wound healing process involves the activation of extracellular matrix components, remodeling enzymes, cellular adhesion molecules, growth factors, cytokines and chemokines genes. However, the molecular patterns underlying the healing process at the periapical environment remain unclear. Here we hypothesized that endodontic infection might result in an imbalance in the expression of wound healing genes involved in the pathogenesis of periapical lesions. Furthermore, we suggest that differential expression of wound healing markers in active and latent granulomas could account for different clinical outcomes for such lesions.
  
  
  METHODS
  Study samples consisted of 93 periapical granulomas collected after endodontic surgeries and 24 healthy periodontal ligament tissues collected from premolars extracted for orthodontic purposes as control samples. Of these, 10 periapical granulomas and 5 healthy periapical tissues were used for expression analysis of 84 wound healing genes by using a pathway-specific real-time polymerase chain reaction array. The remaining 83 granulomas and all 24 control specimens were used to validate the obtained array data by real-time polymerase chain reaction. Observed variations in expression of wound healing genes were analyzed according to the classification of periapical granulomas as active/progressive versus inactive/stable (as determined by receptor activator for nuclear factor kappa B ligand/osteoprotegerin expression ratio).
  
  
  RESULTS
  We observed a marked increase of 5-fold or greater in SERPINE1, TIMP1, COL1A1, COL5A1, VTN, CTGF, FGF7, TGFB1, TNF, CXCL11, ITGA4, and ITGA5 genes in the periapical granulomas when compared with control samples. SERPINE1, TIMP1, COL1A1, TGFB1, and ITGA4 mRNA expression was significantly higher in inactive compared with active periapical granulomas (P < .001), whereas TNF and CXCL11 mRNA expression was higher in active lesions (P < .001).
  
  
  CONCLUSIONS
  The identification of novel gene targets that curb the progression status of periapical lesions might contribute to a more accurate diagnosis and lead to treatment modalities more conducive to endodontic success.
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, University of São Paulo, São Paulo, Brazil.
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.forename: Richard
authors.initials: R
authors.lastname: Horwat
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Ray
authors.forename: Thiago Pompermaier
authors.initials: TP
authors.lastname: Garlet
authors.forename: Elcia Maria
authors.initials: EM
authors.lastname: Silveira
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Campanelli
authors.forename: Ana Paula Favaro
authors.initials: AP
authors.lastname: Trombone
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.forename: Renato Menezes
authors.initials: RM
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D054371:Chemokine CXCL11 / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D000090602:Collagen Type I, alpha 1 Chain; D024062:Collagen Type V / Q000032:analysis; D055513:Connective Tissue Growth Factor / Q000032:analysis; D018450:Disease Progression; D051523:Fibroblast Growth Factor 7 / Q000032:analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D039441:Integrin alpha4 / Q000032:analysis; D039482:Integrin alpha5 / Q000032:analysis; D008875:Middle Aged; D053244:Osteoprotegerin / Q000032:analysis; D010484:Periapical Granuloma / Q000235:genetics*; D010513:Periodontal Ligament / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011480:Protease Inhibitors / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019096:Vitronectin / Q000032:analysis; D014945:Wound Healing / Q000235:genetics; D055815:Young Adult
chemical_list: C526317:CCN2 protein, human; C530725:COL5A1 protein, human; C515202:CXCL11 protein, human; D054371:Chemokine CXCL11; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024062:Collagen Type V; C496453:FGF7 protein, human; D039482:Integrin alpha5; D053244:Osteoprotegerin; D017395:Plasminogen Activator Inhibitor 1; D011480:Protease Inhibitors; D053245:RANK Ligand; C051321:SERPINE1 protein, human; C508960:TGFB1 protein, human; C560822:TIMP1 protein, human; C439524:TNF protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D019096:Vitronectin; D051523:Fibroblast Growth Factor 7; D055513:Connective Tissue Growth Factor; D039441:Integrin alpha4