Arzu Tezvergil-Mutluay1, Kelli A Agee2, Annalisa Mazzoni3, Ricardo M Carvalho4, Marcela Carrilho5, Ivarne L Tersariol6, Fabio D Nascimento7, Satoshi Imazato8, Leo Tjäderhane9, Lorenzo Breschi10, Franklin R Tay2, David H Pashley11. 1. Adhesive Dentistry Research Group, Institute of Dentistry, University of Turku, Turku, Finland. 2. Department of Oral Biology, College of Dental Medicine, Georgia Regents University, Augusta, GA, USA. 3. Department of SAU&FAL, University of Bologna, Bologna, Italy. 4. Department of Oral Science, School of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada. 5. UNIBAN (University Bandeirante Anhanguera), Biomaterials Research Group, Sao Paulo, Brazil. 6. Centro Interdisciplinar de Investigacão Bioquimica, University of Mogi das Cruzes, Mogi das cruzes, Brazil; Department of Biochemistry, Federal University São Paulo, Brazil. 7. Biomaterials Research Group, UNIBAN, São Paulo, Brazil. 8. Osaka University Graduate School of Dentistry, Department of Biomaterials Science, Osaka, Japan. 9. Institute of Dentistry, University of Oulu, Oulu University Hospital, Oulu, Finland; Institute of Dentistry, University of Turku, Turku, Finland. 10. Department of SAU&FAL, University of Bologna, Bologna, Italy; UNIBAN (University Bandeirante Anhanguera), Biomaterials Research Group, Sao Paulo, Brazil. 11. Department of Oral Biology, College of Dental Medicine, Georgia Regents University, Augusta, GA, USA. Electronic address: dpashley@gru.edu.
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. SIGNIFICANCE: CTX seems to be released from dentin matrix only by cathepsin K. MMPs and cathepsin K and B may all contribute to matrix degradation.
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. SIGNIFICANCE: CTX seems to be released from dentin matrix only by cathepsin K. MMPs and cathepsin K and B may all contribute to matrix degradation.
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