Abstract
Objective
This in situ study aimed to evaluate the effects of the inhibitors of matrix metalloproteinases (MMPs) and cysteine cathepsins on dentin erosion.
Materials and methods
Ten volunteers participated in this study. Each volunteer wore an intraoral appliance containing 4 dentin specimens subjected to different treatments: deionized water as a control, 1 mM 1,10-phenanthroline (an MMP inhibitor), 50 µM E-64 (a cysteine cathepsin inhibitor), and 1 mM 1,10-phenanthroline + 50 µM E-64. The specimens were dipped in 5 ml of the respective solutions for 30 min at room temperature and then exposed to in vivo erosive challenges by rinsing with 150 ml of a cola drink (4 × 5 min/day) for 7 days. The substance loss of the specimens was measured by profilometry. The transverse sections of the specimens were examined using scanning electron microscopy. Thereafter, the demineralized organic matrix (DOM) of the specimens was removed using type I collagen enzyme and assessed by performing profilometry. The differences in substance loss and DOM thickness among the groups were analyzed by one-way repeated-measures analysis of variance (ANOVA) and Bonferroni’s test at a level of P < 0.05.
Results
Protease inhibitors significantly reduced substance loss in comparison to that of the control group (all P < 0.05). A significantly thicker DOM was observed for the specimens treated with protease inhibitors than for the control specimens (all P < 0.05). No significant differences in substance loss or DOM thickness were found among the MMP inhibitor, cysteine cathepsin inhibitor, and MMP + cysteine cathepsin inhibitor groups.
Conclusions
The use of MMP and cysteine cathepsin inhibitors was shown to increase the acid resistance of human dentin, which may be due to the preservation of the DOM.
Clinical relevance
The application of protease inhibitors could be considered an appropriate preventive strategy for dentin erosion.
Similar content being viewed by others
References
Kato M, Leite AL, Hannas AR, Buzalaf MA (2010) Gels containing MMP inhibitors prevent dental erosion in situ. J Dent Res 89(5):468–472. https://doi.org/10.1177/0022034510363248
Zarella B, Cardoso CA, Pelá VT, Kato MT, Tjäderhane L, Buzalaf MA (2015) The role of matrix metalloproteinases and cysteine-cathepsins on the progression of dentine erosion. Arch Oral Biol 60(9):1340–1345. https://doi.org/10.1016/j.archoralbio.2015.06.011
Maselli A, Silva TMD, Gonçalves LL, Braga AS, Bresciani E, Magalhães AC, Gonçalves SEP (2022) Effect of fluoride, chlorhexidine or Nd:YAG on the progression of root dentin demineralization after removal of the demineralized organic matrix. J Appl Oral Sci 30:e20210496. https://doi.org/10.1590/1678-7757-2021-0496
Tjäderhane L, Nascimento FD, Breschi L, Mazzoni A, Tersariol IL, Geraldeli S, Tezvergil-Mutluay A, Carrilho MR, Carvalho RM, Tay FR, Pashley DH (2013) Optimizing dentin bond durability: control of collagen degradation by matrix metalloproteinases and cysteine cathepsins. Dent Mater 29(1):116–135. https://doi.org/10.1016/j.dental.2012.08.004
Toledano M, Nieto-Aguilar R, Osorio R, Campos A, Osorio E, Tay F, Alaminos M (2010) Differential expression of matrix metalloproteinase-2 in human coronal and radicular sound and carious dentine. J Dent 38(8):635–640. https://doi.org/10.1016/j.jdent.2010.05.001
Osorio R, Yamauti M, Sauro S, Watson TF, Toledano M (2012) Experimental resin cements containing bioactive fillers reduce matrix metalloproteinase-mediated dentin collagen degradation. J Endod 38(9):1227–1232. https://doi.org/10.1016/j.joen.2012.05.011
Buzalaf M, Kato MT, Hannas AR (2012) The role of matrix metalloproteinases in dental erosion. Adv Dent Res 24(2):72–76. https://doi.org/10.1177/0022034512455029
Tjäderhane L, Buzalaf MA, Carrilho M, Chaussain C (2015) Matrix metalloproteinases and other matrix proteinases in relation to cariology: the era of ‘dentin degradomics.’ Caries Res 49(3):193–208. https://doi.org/10.1159/000363582
Kato M, Leite AL, Hannas AR, Buzalaf MA (2010) Effect of iron on matrix metalloproteinase inhibition and on the prevention of dentine erosion. Caries Res 44(3):309–316. https://doi.org/10.1159/000315932
Barbosa C, Kato MT, Buzalaf MA (2011) Effect of supplementation of soft drinks with green tea extract on their erosive potential against dentine. Aust Dent J 56(3):317–321. https://doi.org/10.1111/j.1834-7819.2011.01338.x
Jiang N, Hong DW, Attin T, Cheng H, Yu H (2020) Quercetin reduces erosive dentin wear: evidence from laboratory and clinical studies. Dent Mater 36(11):1430–1436. https://doi.org/10.1016/j.dental.2020.08.013
Tersariol I, Geraldeli S, Minciotti CL, Nascimento FD, Pääkkönen V, Martins MT, Carrilho MR, Pashley DH, Tay FR, Salo T, Tjäderhane L (2010) Cysteine cathepsins in human dentin-pulp complex. J Endod 36(3):475–481. https://doi.org/10.1016/j.joen.2009.12.034
Scaffa P, Vidal CM, Barros N, Gesteira TF, Carmona AK, Breschi L, Pashley DH, Tjäderhane L, Tersariol IL, Nascimento FD, Carrilho MR (2012) Chlorhexidine inhibits the activity of dental cysteine cathepsins. J Dent Res 91(4):420–425. https://doi.org/10.1177/0022034511435329
Vidal C, Tjäderhane L, Scaffa PM, Tersariol IL, Pashley D, Nader HB, Nascimento FD, Carrilho MR (2014) Abundance of MMPs and cysteine cathepsins in caries-affected dentin. J Dent Res 93(3):269–274. https://doi.org/10.1177/0022034513516979
Bafail A, Carrilho MR, Kishen A, Prakki A (2020) Effect of protease inhibitor specificity on dentin matrix properties. J Mech Behav Biomed Mater 109:103861. https://doi.org/10.1016/j.jmbbm.2020.103861
Mei M, Ito L, Cao Y, Li QL, Chu CH, Lo EC (2014) The inhibitory effects of silver diamine fluorides on cysteine cathepsins. J Dent 42(3):329–335. https://doi.org/10.1016/j.jdent.2013.11.018
Nascimento F, Minciotti CL, Geraldeli S, Carrilho MR, Pashley DH, Tay FR, Nader HB, Salo T, Tjäderhane L, Tersariol IL (2011) Cysteine cathepsins in human carious dentin. J Dent Res 90(4):506–511. https://doi.org/10.1177/0022034510391906
Buzalaf M, Charone S, Tjäderhane L (2015) Role of host-derived proteinases in dentine caries and erosion. Caries Res 49(suppl 1):30–37. https://doi.org/10.1159/000380885
Christensen J, Shastri VP (2015) Matrix-metalloproteinase-9 is cleaved and activated by cathepsin K. BMC Res Notes 8:322. https://doi.org/10.1186/s13104-015-1284-8
Nagase H (1997) Activation mechanisms of matrix metalloproteinases. Biol Chem 378(3–4):151–160
Yu H, Jiang NW, Ye XY, Zheng HY, Attin T, Cheng H (2018) In situ effect of tooth mousse containing CPP-ACP on human enamel subjected to in vivo acid attacks. J Dent 76:40–45. https://doi.org/10.1016/j.jdent.2018.05.021
Tay C, Quah SY, Lui JN, Yu VS, Tan KS (2015) Matrix metalloproteinase inhibitor as an antimicrobial agent to eradicate Enterococcus faecalis biofilm. J Endod 41(6):858–863. https://doi.org/10.1016/j.joen.2015.01.032
Tezvergil-Mutluay A, Mutluay M, Seseogullari-Dirihan R, Agee KA, Key WO, Scheffel DL, Breschi L, Mazzoni A, Tjäderhane L, Nishitani Y, Tay FR, Pashley DH (2013) Effect of phosphoric acid on the degradation of human dentin matrix. J Dent Res 92(1):87–91. https://doi.org/10.1177/0022034512466264
Yang H, Chen R, Attin T, Cheng H, Yu H (2020) Repolishing in situ eroded CAD/CAM restorative materials and human enamel. J Mech Behav Biomed Mater 113:104125. https://doi.org/10.1016/j.jmbbm.2020.104125
Yang H, Hong DW, Attin T, Cheng H, Yu H (2020) Erosion of CAD/CAM restorative materials and human enamel: an in situ/in vivo study. J Mech Behav Biomed Mater 110:103903. https://doi.org/10.1016/j.jmbbm.2020.103903
Hannas A, Kato MT, Cardoso Cde A, Magalhães AC, Pereira JC, Tjäderhane L, Buzalaf MA (2016) Preventive effect of toothpastes with MMP inhibitors on human dentine erosion and abrasion in vitro. J Appl Oral Sci 24(1):61–66. https://doi.org/10.1590/1678-775720150289
Liu B, Cui Y, Lu G, Wei S, Yang Z, Du F, An T, Liu J, Shen G, Chen Z (2021) Small molecule inhibitor E-64 exhibiting the activity against African swine fever virus pS273R. Bioorg Med Chem 35:116055. https://doi.org/10.1016/j.bmc.2021.116055
Naso LG, Martínez Medina JJ, D’Alessandro F, Rey M, Rizzi A, Piro OE, Echeverría GA, Ferrer EG, Williams PAM (2020) Ternary copper(II) complex of 5-hydroxytryptophan and 1,10-phenanthroline with several pharmacological properties and an adequate safety profile. J Inorg Biochem 204:110933. https://doi.org/10.1016/j.jinorgbio.2019.110933
Kometani M, Nonomura K, Tomoo T, Niwa S (2010) Hurdles in the drug discovery of cathepsin K inhibitors. Curr Top Med Chem 10(7):733–744. https://doi.org/10.2174/156802610791113478
Scaffa P, Breschi L, Mazzoni A, Vidal CM, Curci R, Apolonio F, Gobbi P, Pashley D, Tjäderhane L, Tersariol IL, Nascimento FD, Carrilho MR (2017) Co-distribution of cysteine cathepsins and matrix metalloproteases in human dentin. Arch Oral Biol 74:101–107. https://doi.org/10.1016/j.archoralbio.2016.11.011
Osorio R, Yamauti M, Osorio E, Ruiz-Requena ME, Pashley D, Tay F, Toledano M (2011) Effect of dentin etching and chlorhexidine application on metalloproteinase-mediated collagen degradation. Eur J Oral Sci 119(1):79–85. https://doi.org/10.1111/j.1600-0722.2010.00789.x
Tjäderhane L, Larjava H, Sorsa T, Uitto VJ, Larmas M, Salo T (1998) The activation and function of host matrix metalloproteinases in dentin matrix breakdown in caries lesions. J Dent Res 77(8):1622–1629. https://doi.org/10.1177/00220345980770081001
Frassetto A, Breschi L, Turco G, Marchesi G, Di Lenarda R, Tay FR, Pashley DH, Cadenaro M (2016) Mechanisms of degradation of the hybrid layer in adhesive dentistry and therapeutic agents to improve bond durability—a literature review. Dent Mater 32(2):e41–e53. https://doi.org/10.1016/j.dental.2015.11.007
Siklos M, BenAiss M, Thatcher GR (2015) Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors. Acta Pharm Sin B 5(6):506–519. https://doi.org/10.1016/j.apsb.2015.08.001
Hanada K, Tamai M, Yamagishi M, Ohmura S, Sawada J, Tanaka I (1978) Isolation and characterization of E–64, a new thiol protease inhibitor. Agric Biol Chem 42(3):523–528. https://doi.org/10.1080/00021369.1978.10863014
Funding
This work was partially supported by the Joint Fund for Scientific and Technological Innovation of Fujian Province (2019Y9030).
Author information
Authors and Affiliations
Contributions
Hui Yang and Xiu-jiao Lin wrote the original draft and performed the data curation. Qiong Liu did the formal analysis and performed the investigation. Hao Yu did the conceptualization, supervision, and review and editing of the manuscript. All authors have read and approved the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethics approval
All procedures performed in the present study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Ethical approval for the study was granted by the Ethics Committee of School and Hospital of Stomatology, Fujian University (Approval no. 18-FMUSS-21).
Consent to participate
Informed consent was obtained from all participants included in the present study. They were informed verbally and in writing of the advantages and disadvantages of participating in the study.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Yang, H., Lin, Xj., Liu, Q. et al. Effects of protease inhibitors on dentin erosion: an in situ study. Clin Oral Invest 27, 1005–1012 (2023). https://doi.org/10.1007/s00784-022-04657-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00784-022-04657-w