Inhibition of Enzymatic Degradation of Adhesive-Dentin Interfaces

Abstract

Adhesive procedures activate dentin-associated matrix metalloproteinases (MMPs), and so iatrogenically initiate bond degradation. We hypothesized that adding MMP inhibitors to adhesive primers may prevent this endogenous enzymatic degradation, thereby improving bond durability. A non-specific MMP inhibitor (chlorhexidine) and a MMP-2/9-specific inhibitor (SB-3CT) were admixed to the primers of an etch & rinse and a self-etch adhesive, both considered as gold-standard adhesives within their respective categories. For dentin powder exposed to the adhesives under clinical application conditions, gelatin zymography revealed the release of MMP-2 (not of MMP-9) by the etch & rinse adhesive, while no release of enzymes could be detected for the mild self-etch adhesive, most likely because of its limited dentin demineralization effect. The built-in MMP inhibitors appeared effective in reducing bond degradation only for the etch & rinse adhesive, and not for the self-etch adhesive. Water sorption of adhesive interfaces most likely remains the principal mechanism of bond degradation, while endogenous enzymes appear to contribute to bond degradation of only etch & rinse adhesives.

Get full access to this article

View all access options for this article.

References

Boushell LW, Kaku M, Mochida Y, Bagnell R, Yamauchi M (2008). Immunohistochemical localization of matrixmetalloproteinase-2 in human coronal dentin. Arch Oral Biol 53: 109–116.

Brown S, Bernardo MM, Li ZH, Kotra LP, Tanaka Y, Fridman R, et al. (2000). Potent and selective mechanism-based inhibition of gelatinases. J Am Chem Soc 122:6799–6800.

Carrilho MR, Geraldeli S, Tay F, de Goes MF, Carvalho RM, Tjäderhane L, et al. (2007). In vivo preservation of the hybrid layer by chlorhexidine. J Dent Res 86:529–533.

Chaussain-Miller C, Fioretti F, Goldberg M, Menashi S (2006). The role of matrix metalloproteinases (MMPs) in human caries. J Dent Res 85: 22–32.

De Munck J, Van Meerbeek B, Yoshida Y, Inoue S, Vargas M, Suzuki K, et al. (2003). Four-year water degradation of total-etch adhesives bonded to dentin. J Dent Res 82:136–140.

De Munck J, Peumans M, Poitevin A, Lambrechts P, Braem M, Van Meerbeek B (2005a). A critical review of the durability of adhesion to tooth tissue: methods and results. J Dent Res 84:118–132.

De Munck J, Van Meerbeek B, Vargas M, Iracki J, Van Landuyt K, Poitevin A, et al. (2005b). One-day bonding effectiveness of new self-etch adhesives to bur-cut enamel and dentin. Oper Dent 30:39–49.

De Munck J, Ermis RB, Koshiro K, Inoue S, Ikeda T, Sano H, et al. (2007). NaOCl degradation of a HEMA-free all-in-one adhesive bonded to enamel and dentin following two air-blowing techniques. J Dent 35:74–83.

Gendron R, Grenier D, Sorsa T, Mayrand D (1999). Inhibition of the activities of matrix metalloproteinases 2, 8, and 9 by chlorhexidine. Clin Diagn Lab Immunol 6:437–439.

10.

Hebling J, Pashley DH, Tjäderhane L, Tay FR (2005). Chlorhexidine arrests subclinical degradation of dentin hybrid layers in vivo. J Dent Res 84:741–746; erratum in J Dent Res 85:384, 2006.

11.

Hu J, Van den Steen PE, Sang QX, Opdenakker G (2007). Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 6:480–498.

12.

Kjeldsen L, Johnsen AH, Sengeløv H, Borregaard N (1993). Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem 268:10425–10432.

13.

Martin-De Las Heras S, Valenzuela A, Overall CM (2000). The matrix metalloproteinase gelatinase A in human dentine. Arch Oral Biol 45:757–765.

14.

Masure S, Billiau A, Van Damme J, Opdenakker G (1990). Human hepatoma cells produce an 85 kDa gelatinase regulated by phorbol 12-myristate 13-acetate. Biochim Biophys Acta 1054:317–325.

15.

Mazzoni A, Mannello F, Tay FR, Tonti GA, Papa S, Mazzotti G, et al. (2007). Zymographic analysis and characterization of MMP-2 and -9 forms in human sound dentin. J Dent Res 86:436–440; erratum in J Dent Res 86:792, 2007.

16.

Mazzoni A, Pashley DH, Tay FR, Gobbi P, Orsini G, Ruggeri A Jr, et al. (2008). Immunohistochemical identification of MMP-2 and MMP-9 in human dentin: correlative FEI-SEM/TEM analysis. J Biomed Mater Res A 88:697–703.

17.

Negrelo Newton AP, Cadena SM, Merlin Rocha ME, Skäre Carnieri EG, Martinelli de Oliveira MB (2004). New data on biological effects of chlorhexidine: Fe2+ induced lipid peroxidation and mitochondrial permeability transition. Toxicol Lett 151:407–416.

18.

Nishitani Y, Yoshiyama M, Wadgaonkar B, Breschi L, Mannello F, Mazzoni A, et al. (2006). Activation of gelatinolytic/collagenolytic activity in dentin by self-etching adhesives. Eur J Oral Sci 114:160–166.

19.

Nishiyama N, Tay FR, Fujita K, Pashley DH, Ikemura K, Hiraishi N, et al. (2006). Hydrolysis of functional monomers in a single-bottle self-etching primer—correlation of 13C NMR and TEM findings. J Dent Res 85: 422–426.

20.

Pashley DH, Tay FR, Yiu C, Hashimoto M, Breschi L, Carvalho RM, et al. (2004). Collagen degradation by host-derived enzymes during aging. J Dent Res 83:216–221.

21.

Poitevin A, De Munck J, Van Landuyt K, Coutinho E, Peumans M, Lambrechts P, et al. (2007). Influence of three specimen fixation modes on the micro-tensile bond strength of adhesives to dentin. Dent Mater J 26:694–699.

22.

Sulkala M , Tervahartiala T, Sorsa T, Larmas M, Salo T, Tjäderhane L (2007). Matrix metalloproteinase-8 (MMP-8) is the major collagenase in human dentin. Arch Oral Biol 52:121–127.

23.

Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G (2002). Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536.

24.

Van den Steen PE, Van Aelst I, Hvidberg V, Piccard H, Fiten P, Jacobsen C, et al. (2006). The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. J Biol Chem 281:18626–18637.

25.

Van Meerbeek B, Vargas M, Inoue S, Yoshida Y, Perdigão J, Lambrechts P, et al. (2000). Microscopy investigations. Techniques, results, limitations. Am J Dent 13(Spec Iss):3D–18D.