title: Runt-related gene 2 is involved in the inhibition of matrix metalloproteinase-13 expression by roxithromycin in human gingival epithelial cell cultures.
abstract: OBJECTIVE
  Matrix metalloproteinase (MMP)-13 has wide substrate specificity compared with other MMPs and appears to be involved in periodontitis. Previously, we reported that roxithromycin (RXM) inhibits vascular endothelial growth factor expression induced by tumour necrosis factor-alpha in human periodontal ligament cells, but little is known about the effect of RXM on MMP-13 expression in human gingival epithelial cells. We therefore examined the effect of RXM on MMP-13 mRNA expression and production in cultured human gingival epithelial cells.
  
  
  METHODS
  Human epithelial cell lines (Ca9-22, TU4, SCCTF and HSC-3) were plated in tissue culture dishes. Then, the culture supernatants and sediments were collected and the production of MMP-13 was analysed using enzyme-linked immunosorbent assay; the expression of MMP-13 mRNA and runt-related gene 2 mRNA was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. We also studied the effect of Runx2 short interfering RNA (siRNA) on the induction of MMP-13.
  
  
  RESULTS
  Roxithromycin downregulated the induction of MMP-13 in Ca9-22 cells. Roxithromycin suppressed the expression of MMP-13 mRNA not only in Ca9-22 cells, but also in other human epithelial cell lines. Roxithromycin strongly inhibited the expression of Runx2 mRNA. Furthermore, Runx2 siRNA inhibited the induction of MMP-13 in Ca9-22 cells.
  
  
  CONCLUSIONS
  These results indicate that RXM suppresses MMP-13 via the downregulation of Runx2 in human gingival epithelial cell cultures.
authors.affiliation: Department of Restorative Dentistry and Endodontology, Kagoshima University, Kagoshima, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Tabuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sakuta
authors.forename: Tohru
authors.initials: T
authors.lastname: Oyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tokuda
authors.forename: Syouko
authors.initials: S
authors.lastname: Tatsuyama
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kajihara
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Nagaoka
authors.forename: Mahiro
authors.initials: M
authors.lastname: Beppu
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Sugihara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ikebe
authors.forename: Kanemitsu
authors.initials: K
authors.lastname: Shirasuna
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Torii
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D015536:Down-Regulation; D004790:Enzyme Induction / Q000187:drug effects*; D004847:Epithelial Cells / Q000201:enzymology; D005881:Gingiva / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000502:physiology; D015575:Roxithromycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D050659:Core Binding Factor Alpha 1 Subunit; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C493709:RUNX2 protein, human; D015575:Roxithromycin; D053509:Matrix Metalloproteinase 13