title: DNA Methylation of MMP9 Is Associated with High Levels of MMP-9 Messenger RNA in Periapical Inflammatory Lesions.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are the major class of enzymes responsible for degradation of extracellular matrix components and participate in the pathogenesis of periapical inflammatory lesions. MMP expression may be regulated by DNA methylation. The purpose of the present investigation was to analyze the expression of MMP2 and MMP9 in periapical granulomas and radicular cysts and to test the hypothesis that, in these lesions, their transcription may be modulated by DNA methylation.
  
  
  METHODS
  Methylation-specific polymerase chain reaction was used to evaluate the DNA methylation pattern of the MMP2 gene in 13 fresh periapical granuloma samples and 10 fresh radicular cyst samples. Restriction enzyme digestion was used to assess methylation of the MMP9 gene in 12 fresh periapical granuloma samples and 10 fresh radicular cyst samples. MMP2 and MMP9 messenger RNA transcript levels were measured by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  All periapical lesions and healthy mucosa samples showed partial methylation of the MMP2 gene; however, periapical granulomas showed higher MMP2 mRNA expression levels than healthy mucosa (P = .014). A higher unmethylated profile of the MMP9 gene was found in periapical granulomas and radicular cysts compared with healthy mucosa. In addition, higher MMP9 mRNA expression was observed in the periapical lesions compared with healthy tissues.
  
  
  CONCLUSIONS
  The present study suggests that the unmethylated status of the MMP9 gene in periapical lesions may explain the observed up-regulation of messenger RNA transcription in these lesions.
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Kelma
authors.initials: K
authors.lastname: Campos
authors.affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Carolina Cavalieri
authors.initials: CC
authors.lastname: Gomes
authors.affiliation: Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Brazil.
authors.forename: Lucyana Conceição
authors.initials: LC
authors.lastname: Farias
authors.affiliation: Department of Endodontics and Center for Craniofacial Research, University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas.
authors.forename: Renato Menezes
authors.initials: RM
authors.lastname: Silva
authors.affiliation: Department of Endodontics and Center for Craniofacial Research, University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas.
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: rsgomez@ufmg.br.
authors.forename: Ricardo Santiago
authors.initials: RS
authors.lastname: Gomez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019175:DNA Methylation; D005260:Female; D006099:Granuloma / Q000235:genetics; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D010510:Periodontal Diseases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011842:Radicular Cyst / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Matrix metalloproteinase; messenger RNA; methylation; periapical lesion; radicular cyst; transcription