title: Can quaternary ammonium methacrylates inhibit matrix MMPs and cathepsins?
abstract: OBJECTIVE
  Dentin matrices release ICTP and CTX fragments during collagen degradation. ICTP fragments are known to be produced by MMPs. CTX fragments are thought to come from cathepsin K activity. The purpose of this study was to determine if quaternary methacrylates (QAMs) can inhibit matrix MMPs and cathepsins.
  
  
  METHODS
  Dentin beams were demineralizated, and dried to constant weight. Beams were incubated with rh-cathepsin B, K, L or S for 24h at pH 7.4 to identify which cathepsins release CTX at neutral pH. Beams were dipped in ATA, an antimicrobial QAM to determine if it can inhibit dentin matrix proteases. Other beams were dipped in another QAM (MDPB) to determine if it produced similar inhibition of dentin proteases.
  
  
  RESULTS
  Only beams incubated with cathepsin K lost more dry mass than the controls and released CTX. Dentin beams dipped in ATA and incubated for 1 week at pH 7.4, showed a concentration-dependent reduction in weight-loss. There was no change in ICTP release from control values, meaning that ATA did not inhibit MMPs. Media concentrations of CTX fell significantly at 15wt% ATA indicating that ATA inhibits capthesins. Beams dipped in increasing concentrations of MDPB lost progressively less mass, showing that MDPB is a protease-inhibitor. ICTP released from controls or beams exposed to low concentrations were the same, while 5 or 10% MDPB significantly lowered ICTP production. CTX levels were strongly inhibited by 2.5-10% MDPB, indicating that MDPB is a potent inhibitor of both MMPs and cathepsin K.
  
  
  CONCLUSIONS
  CTX seems to be released from dentin matrix only by cathepsin K. MMPs and cathepsin K and B may all contribute to matrix degradation.
authors.affiliation: Adhesive Dentistry Research Group, Institute of Dentistry, University of Turku, Turku, Finland.
authors.forename: Arzu
authors.initials: A
authors.lastname: Tezvergil-Mutluay
authors.affiliation: Department of Oral Biology, College of Dental Medicine, Georgia Regents University, Augusta, GA, USA.
authors.forename: Kelli A
authors.initials: KA
authors.lastname: Agee
authors.affiliation: Department of SAU&FAL, University of Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mazzoni
authors.affiliation: Department of Oral Science, School of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Carvalho
authors.affiliation: UNIBAN (University Bandeirante Anhanguera), Biomaterials Research Group, Sao Paulo, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Carrilho
authors.affiliation: Centro Interdisciplinar de Investigacão Bioquimica, University of Mogi das Cruzes, Mogi das cruzes, Brazil; Department of Biochemistry, Federal University São Paulo, Brazil.
authors.forename: Ivarne L
authors.initials: IL
authors.lastname: Tersariol
authors.affiliation: Biomaterials Research Group, UNIBAN, São Paulo, Brazil.
authors.forename: Fabio D
authors.initials: FD
authors.lastname: Nascimento
authors.affiliation: Osaka University Graduate School of Dentistry, Department of Biomaterials Science, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imazato
authors.affiliation: Institute of Dentistry, University of Oulu, Oulu University Hospital, Oulu, Finland; Institute of Dentistry, University of Turku, Turku, Finland.
authors.forename: Leo
authors.initials: L
authors.lastname: Tjäderhane
authors.affiliation: Department of SAU&FAL, University of Bologna, Bologna, Italy; UNIBAN (University Bandeirante Anhanguera), Biomaterials Research Group, Sao Paulo, Brazil.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Breschi
authors.affiliation: Department of Oral Biology, College of Dental Medicine, Georgia Regents University, Augusta, GA, USA.
authors.forename: Franklin R
authors.initials: FR
authors.lastname: Tay
authors.affiliation: Department of Oral Biology, College of Dental Medicine, Georgia Regents University, Augusta, GA, USA. Electronic address: dpashley@gru.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: Pashley
mesh_terms: D064751:Ammonium Compounds / Q000494:pharmacology*; D056657:Cathepsin K / Q000378:metabolism* / Q000494:pharmacology; D003804:Dentin / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism* / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology*
chemical_list: D064751:Ammonium Compounds; D008689:Methacrylates; D056657:Cathepsin K; D020782:Matrix Metalloproteinases
keywords: CTX; Cathepsins; Degradation of collagen; ICTP; MMPs; Quaternary ammonium compounds