title: Altered gene expression levels of matrix metalloproteinases and their inhibitors in periodontitis-affected gingival tissue.
abstract: BACKGROUND
  The balance between the degradation and synthesis of extracellular matrix determines periodontal attachment levels and alveolar bone matrix concentration in periodontal diseases. Matrix metalloproteinases (MMPs) are known to degrade periodontal ligamental attachment and bone matrix proteins. The purpose of this study was to examine the effect of different expression levels of MMPs and their inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), in periodontitis.
  
  
  METHODS
  Sixteen inflamed gingival tissue samples from subjects with generalized chronic periodontitis and 14 control tissue samples from systemically and periodontally healthy subjects were evaluated. The total RNA was extracted, and the transcript levels for MMP-1, -3, -9, and -13 and TIMP-1, -2, -3, and -4 relative to beta-actin were determined by quantitative real-time reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Gene transcript levels for MMP-1 and TIMP-4 were significantly higher in periodontitis-affected gingival tissues (P <0.05). MMP-3, -9, and -13 and TIMP-1 mRNAs also were elevated in periodontitis; however, the difference was not statistically significant. TIMP-2 and -3 mRNA levels were similar in healthy and diseased gingivae. The ratios of MMP-1/TIMP-2 (P <0.01), MMP-3/TIMP-2 (P <0.05), MMP-9/TIMP-2 (P <0.05), and MMP-1/TIMP-3 (P <0.01) from periodontitis lesions were significantly higher than those in the control tissues.
  
  
  CONCLUSIONS
  Upregulated MMP expression and an increased MMP/TIMP ratio indicate that a potential imbalance between degradation and synthesis of extracellular matrix persists in periodontitis-affected gingival tissues. This process may be responsible for increased tissue breakdown in periodontitis.
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Course for Oral Life Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. kubota@dent.niigata-u.ac.jp
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kubota
authors.forename: Manami
authors.initials: M
authors.lastname: Itagaki
authors.forename: Chika
authors.initials: C
authors.lastname: Hoshino
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagata
authors.forename: Toshiya
authors.initials: T
authors.lastname: Morozumi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Ritsuo
authors.initials: R
authors.lastname: Takagi
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yoshie
mesh_terms: D000199:Actins / Q000032:analysis; D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005881:Gingiva / Q000201:enzymology; D005891:Gingivitis / Q000201:enzymology*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis* / Q000235:genetics; D010518:Periodontitis / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis* / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D000199:Actins; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020782:Matrix Metalloproteinases; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C088390:TIMP3 protein, human; C507079:MMP13 protein, human; C511768:MMP3 protein, human; C522360:MMP1 protein, human