title: Gelatinases and extracellular matrix metalloproteinase inducer are associated with cyclosporin-A-induced attenuation of periodontal degradation in rats.
abstract: BACKGROUND
  The present study aims to examine the inhibitory effect of cyclosporin-A (CsA) on periodontal breakdown and to further explore the correlations of CsA-induced attenuation of periodontal bone loss with the expressions of gelatinases (i.e., matrix metalloproteinase [MMP]-2 and MMP-9) and extracellular matrix metalloproteinase inducer (EMMPRIN).
  
  
  METHODS
  Forty Sprague-Dawley rats were randomly divided into four groups: 1) control; 2) CsA; 3) ligature (Lig); and 4) ligature plus CsA (Lig + CsA). The CsA group received 10 mg ⋅ Kg(-1) ⋅ d(-1) CsA for 8 days. The Lig group received silk ligature on selected molars. The Lig + CsA group received silk ligature and CsA treatment. The inhibitory effects of CsA on the ligature-induced periodontal breakdown was examined with microcomputed tomography (micro-CT) and histometric analyses to analyze the amount of attachment loss, crestal bone loss, connective tissue attachment, and the surface area with inflammatory cell infiltration. The effects of CsA on ligature-induced expressions of gelatinases and EMMPRIN in gingival tissues were examined with Western blotting and zymography, respectively.
  
  
  RESULTS
  By micro-CT and histology, the Lig + CsA group had significantly more periodontal breakdown than the control and CsA groups but less periodontal breakdown than the Lig group. Consistent results were found for the expressions of gelatinases and EMMPRIN among the groups demonstrating that the Lig + CsA group had significantly less gingival protein expression of gelatinases and EMMPRIN than the Lig group.
  
  
  CONCLUSIONS
  CsA inhibited the expressions of gelatinase MMPs and EMMPRIN and partially prevented the periodontal breakdown in ligature-induced experimental periodontitis. The CsA-induced attenuation of periodontal bone loss was strongly correlated positively with the expressions of MMP-2, MMP-9, and EMMPRIN in gingiva.
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Martin Ming-Jen
authors.initials: MM
authors.lastname: Fu
authors.forename: Earl
authors.initials: E
authors.lastname: Fu
authors.forename: Po-Jan
authors.initials: PJ
authors.lastname: Kuo
authors.forename: Hsiao-Pei
authors.initials: HP
authors.lastname: Tu
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Chin
authors.forename: Cheng-Yang
authors.initials: CY
authors.lastname: Chiang
authors.forename: Hsien-Chung
authors.initials: HC
authors.lastname: Chiu
mesh_terms: D016301:Alveolar Bone Loss / Q000201:enzymology / Q000517:prevention & control; D000818:Animals; D051926:Basigin / Q000187:drug effects*; D003238:Connective Tissue / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology; D005891:Gingivitis / Q000201:enzymology / Q000517:prevention & control; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D017622:Periodontal Attachment Loss / Q000201:enzymology / Q000517:prevention & control; D010518:Periodontitis / Q000201:enzymology* / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D051926:Basigin; D016572:Cyclosporine; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Alveolar bone loss; CD147; antigens; cyclosporine; gelatinases; matrix metalloproteinases; periodontitis