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Dentin Degradation: From Tissue Breakdown to Possibilities for Therapeutic Intervention

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Abstract

Purpose of the Review

Presently, dental materials science is driven by the search for new and improved materials that can trigger specific reactions from the affected tissue to stimulate repair or regeneration while interacting with the oral environment to promote or maintain oral health. In parallel, evidence from the past decades has challenged the exclusive role of bacteria in dentin tissue degradation in caries, questioning our understanding of caries etiopathogenesis. The goal of this review is to recapitulate the current evidence on the host and bacterial contributions to degradation, inflammation, and repair of the dentin-pulp complex in caries.

Recent Findings

Contrasting findings attribute dentin breakdown to the activity of endogenous enzymes, such as matrix metalloproteinases (MMPs) and cathepsins, while the role of bacteria and their by-products in the destruction of dentin organic matrix and pulp inflammation has been for decades supported as an incontestable paradigm. Aiming to better understand the mechanisms involved in collagen degradation by host enzymes in caries, studies have showed that these proteinases are expressed in the mature dentin (i.e., after dentin formation) and become activated by the low pH in the acidic environment resulted by bacterial metabolism in caries. However, different host sources other than dentin-bound proteinases seem to also contribute to caries progression, such as saliva and pulp. Interestingly, studies evaluating pulp responses to bacteria invasion and inflammation in caries report higher levels of MMPs and cathepsins in inflamed tissue, but also showed MMP potential to resolve inflammation and stimulate wound healing. Notably, as reported for other tissues, MMPs exert dual roles in the dentin-pulp complex in caries, participating or regulating both degradative and reparative mechanisms.

Summary

The specific roles of host and bacteria and their by-products in caries progression have yet to be clarified. The complex interactions between inflammation and repair in caries pose challenges to a clear understanding of the dentin-pulp complex responses and changes to bacteria invasion. However, it opens new venues for the development of novel therapies and dental biomaterials based on the modulation of specific mechanisms to favor tissue repair and healing.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Jain N, Dutt U, Radenkov I, Jain S. WHO's global oral health status report 2022: actions, discussion and implementation. Oral Dis 2023. https://doi.org/10.1111/odi.14516

  2. Featherstone JDB, Chaffee BW. The Evidence for Caries Management by Risk Assessment (CAMBRA(R)). Adv Dent Res. 2018;29(1):9–14. https://doi.org/10.1177/0022034517736500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Giacaman RA, Fernandez CE, Munoz-Sandoval C, Leon S, Garcia-Manriquez N, Echeverria C, et al. Understanding dental caries as a non-communicable and behavioral disease: management implications. Front Oral Health. 2022;3:764479. https://doi.org/10.3389/froh.2022.764479.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Slayton RL, Urquhart O, Araujo MWB, Fontana M, Guzman-Armstrong S, Nascimento MM, et al. Evidence-based clinical practice guideline on nonrestorative treatments for carious lesions: a report from the American Dental Association. J Am Dent Assoc. 2018;149(10):837-49 e19. https://doi.org/10.1016/j.adaj.2018.07.002.

    Article  PubMed  Google Scholar 

  5. Schwendicke F, Walsh T, Lamont T, Al-Yaseen W, Bjorndal L, Clarkson JE, et al. Interventions for treating cavitated or dentine carious lesions. Cochrane Database Syst Rev. 2021;7(7):CD013039. https://doi.org/10.1002/14651858.CD013039.pub2.

    Article  PubMed  Google Scholar 

  6. Yun J, Burrow MF, Matinlinna JP, Wang Y, Tsoi JKH. A narrative review of bioactive glass-loaded dental resin composites. J Funct Biomater 2022;13(4). https://doi.org/10.3390/jfb13040208

  7. Bacino M, Girn V, Nurrohman H, Saeki K, Marshall SJ, Gower L, et al. Integrating the PILP-mineralization process into a restorative dental treatment. Dent Mater. 2019;35(1):53–63. https://doi.org/10.1016/j.dental.2018.11.030.

    Article  CAS  PubMed  Google Scholar 

  8. Trevelin LT, Alania Y, Mathew M, Phansalkar R, Chen SN, Pauli GF, et al. Effect of dentin biomodification delivered by experimental acidic and neutral primers on resin adhesion. J Dent. 2020;99:103354. https://doi.org/10.1016/j.jdent.2020.103354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bedran-Russo AK, Pauli GF, Chen SN, McAlpine J, Castellan CS, Phansalkar RS, et al. Dentin biomodification: strategies, renewable resources and clinical applications. Dent Mater. 2014;30(1):62–76. https://doi.org/10.1016/j.dental.2013.10.012.

    Article  CAS  PubMed  Google Scholar 

  10. Fugolin AP, Dobson A, Huynh V, Mbiya W, Navarro O, Franca CM, et al. Antibacterial, ester-free monomers: polymerization kinetics, mechanical properties, biocompatibility and anti-biofilm activity. Acta Biomater. 2019;100:132–41. https://doi.org/10.1016/j.actbio.2019.09.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Emara R, Elhennawy K, Schwendicke F. Effects of calcium silicate cements on dental pulp cells: a systematic review. J Dent. 2018;77:18–36. https://doi.org/10.1016/j.jdent.2018.08.003.

    Article  CAS  PubMed  Google Scholar 

  12. Marshall GW, Habelitz S, Gallagher R, Balooch M, Balooch G, Marshall SJ. Nanomechanical properties of hydrated carious human dentin. J Dent Res. 2001;80(8):1768–71. https://doi.org/10.1177/00220345010800081701.

    Article  CAS  PubMed  Google Scholar 

  13. Liu Y, Yao X, Liu YW, Wang Y. A Fourier transform infrared spectroscopy analysis of carious dentin from transparent zone to normal zone. Caries Res. 2014;48(4):320–9. https://doi.org/10.1159/000356868.

    Article  CAS  PubMed  Google Scholar 

  14. Dayan D, Binderman I, Mechanic GL. A preliminary study of activation of collagenase in carious human dentine matrix. Arch Oral Biol. 1983;28(2):185–7. https://doi.org/10.1016/0003-9969(83)90126-7.

    Article  CAS  PubMed  Google Scholar 

  15. van Strijp AJ, van Steenbergen TJ, de Graaff J, ten Cate JM. Bacterial colonization and degradation of demineralized dentin matrix in situ. Caries Res. 1994;28(1):21–7. https://doi.org/10.1159/000261615.

    Article  PubMed  Google Scholar 

  16. Tjaderhane L, Larjava H, Sorsa T, Uitto VJ, Larmas M, Salo T. The activation and function of host matrix metalloproteinases in dentin matrix breakdown in caries lesions. J Dent Res. 1998;77(8):1622–9. https://doi.org/10.1177/00220345980770081001.

    Article  CAS  PubMed  Google Scholar 

  17. Sulkala M, Wahlgren J, Larmas M, Sorsa T, Teronen O, Salo T, et al. The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats. J Dent Res. 2001;80(6):1545–9. https://doi.org/10.1177/00220345010800061301.

    Article  CAS  PubMed  Google Scholar 

  18. Nascimento FD, Minciotti CL, Geraldeli S, Carrilho MR, Pashley DH, Tay FR, et al. Cysteine cathepsins in human carious dentin. J Dent Res. 2011;90(4):506–11. https://doi.org/10.1177/0022034510391906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kuhn E, Reis A, Campagnoli EB, Chibinski AC, Carrilho MR, Wambier DS. Effect of sealing infected dentin with glass ionomer cement on the abundance and localization of MMP-2, MMP-8, and MMP-9 in young permanent molars in vivo. Int J Paediatr Dent. 2016;26(2):125–33. https://doi.org/10.1111/ipd.12167.

    Article  PubMed  Google Scholar 

  20. Chibinski AC, Gomes JR, Camargo K, Reis A, Wambier DS. Bone sialoprotein, matrix metalloproteinases and type I collagen expression after sealing infected caries dentin in primary teeth. Caries Res. 2014;48(4):312–9. https://doi.org/10.1159/000355302.

    Article  CAS  PubMed  Google Scholar 

  21. Goldberg M, Keil B. Action of a bacterial Achromobacter collagenase on the soft carious dentine: an in vitro study with the scanning electron microscope. J Biol Buccale. 1989;17(4):269–74.

    CAS  PubMed  Google Scholar 

  22. Nyvad B, Fejerskov O. An ultrastructural study of bacterial invasion and tissue breakdown in human experimental root-surface caries. J Dent Res. 1990;69(5):1118–25. https://doi.org/10.1177/00220345900690050101.

    Article  CAS  PubMed  Google Scholar 

  23. van Strijp AJ, van Steenbergen TJ, ten Cate JM. Bacterial colonization of mineralized and completely demineralized dentine in situ. Caries Res. 1997;31(5):349–55. https://doi.org/10.1159/000262417.

    Article  PubMed  Google Scholar 

  24. Huang B, Stewart CA, McCulloch CA, Santerre JP, Cvitkovitch DG, Finer Y. Streptococcus mutans proteases degrade dentinal collagen. Dentistry Journal. 2022;10(12):223.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Crowley PJ, Brady LJ, Michalek SM, Bleiweis AS. Virulence of a spaP mutant of Streptococcus mutans in a gnotobiotic rat model. Infect Immun. 1999;67(3):1201–6. https://doi.org/10.1128/IAI.67.3.1201-1206.1999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tjaderhane L, Buzalaf MA, Carrilho M, Chaussain C. Matrix metalloproteinases and other matrix proteinases in relation to cariology: the era of “dentin degradomics.” Caries Res. 2015;49(3):193–208. https://doi.org/10.1159/000363582.

    Article  CAS  PubMed  Google Scholar 

  27. Cui N, Hu M, Khalil RA. Biochemical and biological attributes of matrix metalloproteinases. Prog Mol Biol Transl Sci. 2017;147:1–73. https://doi.org/10.1016/bs.pmbts.2017.02.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003;92(8):827–39. https://doi.org/10.1161/01.RES.0000070112.80711.3D.

    Article  CAS  PubMed  Google Scholar 

  29. Mazzoni A, Mannello F, Tay FR, Tonti GA, Papa S, Mazzotti G, et al. Zymographic analysis and characterization of MMP-2 and -9 forms in human sound dentin. J Dent Res. 2007;86(5):436–40. https://doi.org/10.1177/154405910708600509.

    Article  CAS  PubMed  Google Scholar 

  30. Mazzoni A, Maravic T, Tezvergil-Mutluay A, Tjaderhane L, Scaffa PMC, Seseogullari-Dirihan R, et al. Biochemical and immunohistochemical identification of MMP-7 in human dentin. J Dent. 2018;79:90–5. https://doi.org/10.1016/j.jdent.2018.10.008.

    Article  CAS  PubMed  Google Scholar 

  31. Mazzoni A, Papa V, Nato F, Carrilho M, Tjaderhane L, Ruggeri A Jr, et al. Immunohistochemical and biochemical assay of MMP-3 in human dentine. J Dent. 2011;39(3):231–7. https://doi.org/10.1016/j.jdent.2011.01.001.

    Article  CAS  PubMed  Google Scholar 

  32. Mazzoni A, Pashley DH, Tay FR, Gobbi P, Orsini G, Ruggeri A Jr, et al. Immunohistochemical identification of MMP-2 and MMP-9 in human dentin: correlative FEI-SEM/TEM analysis. J Biomed Mater Res A. 2009;88(3):697–703. https://doi.org/10.1002/jbm.a.31920.

    Article  CAS  PubMed  Google Scholar 

  33. Sulkala M, Larmas M, Sorsa T, Salo T, Tjaderhane L. The localization of matrix metalloproteinase-20 (MMP-20, enamelysin) in mature human teeth. J Dent Res. 2002;81(9):603–7. https://doi.org/10.1177/154405910208100905.

    Article  CAS  PubMed  Google Scholar 

  34. Palosaari H, Pennington CJ, Larmas M, Edwards DR, Tjaderhane L, Salo T. Expression profile of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in mature human odontoblasts and pulp tissue. Eur J Oral Sci. 2003;111(2):117–27. https://doi.org/10.1034/j.1600-0722.2003.00026.x.

    Article  CAS  PubMed  Google Scholar 

  35. Martin-De Las Heras S, Valenzuela A, Overall CM. The matrix metalloproteinase gelatinase A in human dentine. Arch Oral Biol. 2000;45(9):757–65. https://doi.org/10.1016/s0003-9969(00)00052-2.

    Article  CAS  PubMed  Google Scholar 

  36. Ballal V, Rao S, Bagheri A, Bhat V, Attin T, Zehnder M. MMP-9 in dentinal fluid correlates with caries lesion depth. Caries Res. 2017;51(5):460–5. https://doi.org/10.1159/000479040.

    Article  CAS  PubMed  Google Scholar 

  37. Vidal CM, Tjaderhane L, Scaffa PM, Tersariol IL, Pashley D, Nader HB, et al. Abundance of MMPs and cysteine cathepsins in caries-affected dentin. J Dent Res. 2014;93(3):269–74. https://doi.org/10.1177/0022034513516979.

    Article  CAS  PubMed  Google Scholar 

  38. Boushell LW, Nagaoka H, Nagaoka H, Yamauchi M. Increased matrix metalloproteinase-2 and bone sialoprotein response to human coronal caries. Caries Res. 2011;45(5):453–9. https://doi.org/10.1159/000330601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Shimada Y, Ichinose S, Sadr A, Burrow MF, Tagami J. Localization of matrix metalloproteinases (MMPs-2, 8, 9 and 20) in normal and carious dentine. Aust Dent J. 2009;54(4):347–54. https://doi.org/10.1111/j.1834-7819.2009.01161.x.

    Article  CAS  PubMed  Google Scholar 

  40. Toledano M, Nieto-Aguilar R, Osorio R, Campos A, Osorio E, Tay FR, et al. Differential expression of matrix metalloproteinase-2 in human coronal and radicular sound and carious dentine. J Dent. 2010;38(8):635–40. https://doi.org/10.1016/j.jdent.2010.05.001.

    Article  CAS  PubMed  Google Scholar 

  41. Amaral SFD, Scaffa PMC, Rodrigues RDS, Nesadal D, Marques MM, Nogueira FN, et al. Dynamic influence of pH on metalloproteinase activity in human coronal and radicular dentin. Caries Res. 2018;52(1–2):113–8. https://doi.org/10.1159/000479825.

    Article  CAS  PubMed  Google Scholar 

  42. Vidak E, Javorsek U, Vizovisek M, Turk B. Cysteine cathepsins and their extracellular roles: shaping the microenvironment. Cells. 2019;8(3). https://doi.org/10.3390/cells8030264.

  43. Carrilho MR, Scaffa P, Oliveira V, Tjaderhane L, Tersariol IL, Pashley DH, et al. Insights into cathepsin-B activity in mature dentin matrix. Arch Oral Biol. 2020;117:104830. https://doi.org/10.1016/j.archoralbio.2020.104830.

    Article  CAS  PubMed  Google Scholar 

  44. Scaffa PM, Breschi L, Mazzoni A, Vidal CM, Curci R, Apolonio F, et al. Co-distribution of cysteine cathepsins and matrix metalloproteases in human dentin. Arch Oral Biol. 2017;74:101–7. https://doi.org/10.1016/j.archoralbio.2016.11.011.

    Article  CAS  PubMed  Google Scholar 

  45. Nagase H, Suzuki K, Morodomi T, Enghild JJ, Salvesen G. Activation mechanisms of the precursors of matrix metalloproteinases 1, 2 and 3. Matrix Suppl. 1992;1:237–44.

    CAS  PubMed  Google Scholar 

  46. Okamoto T, Akaike T, Suga M, Tanase S, Horie H, Miyajima S, et al. Activation of human matrix metalloproteinases by various bacterial proteinases. J Biol Chem. 1997;272(9):6059–66. https://doi.org/10.1074/jbc.272.9.6059.

    Article  CAS  PubMed  Google Scholar 

  47. DeCarlo AA Jr, Windsor LJ, Bodden MK, Harber GJ, Birkedal-Hansen B, Birkedal-Hansen H. Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis. J Dent Res. 1997;76(6):1260–70. https://doi.org/10.1177/00220345970760060501.

    Article  CAS  PubMed  Google Scholar 

  48. Zhou J, Windsor LJ. Porphyromonas gingivalis affects host collagen degradation by affecting expression, activation, and inhibition of matrix metalloproteinases. J Periodontal Res. 2006;41(1):47–54. https://doi.org/10.1111/j.1600-0765.2005.00835.x.

    Article  CAS  PubMed  Google Scholar 

  49. Bafail A, Carneiro KMM, Kishen A, Prakki A. Effect of odanacatib on the release of NTX (amino terminal telopeptide) from LPS contaminated type I dentin collagen. Dent Mater. 2023;39(2):162–9. https://doi.org/10.1016/j.dental.2022.12.004.

    Article  CAS  PubMed  Google Scholar 

  50. Zhang YZ, Ran LY, Li CY, Chen XL. Diversity, structures, and collagen-degrading mechanisms of bacterial collagenolytic proteases. Appl Environ Microbiol. 2015;81(18):6098–107. https://doi.org/10.1128/AEM.00883-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mazzoni A, Tjaderhane L, Checchi V, Di Lenarda R, Salo T, Tay FR, et al. Role of dentin MMPs in caries progression and bond stability. J Dent Res. 2015;94(2):241–51. https://doi.org/10.1177/0022034514562833.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Suppa P, Ruggeri A Jr, Tay FR, Prati C, Biasotto M, Falconi M, et al. Reduced antigenicity of type I collagen and proteoglycans in sclerotic dentin. J Dent Res. 2006;85(2):133–7. https://doi.org/10.1177/154405910608500204.

    Article  CAS  PubMed  Google Scholar 

  53. Deyhle H, Bunk O, Muller B. Nanostructure of healthy and caries-affected human teeth. Nanomedicine. 2011;7(6):694–701. https://doi.org/10.1016/j.nano.2011.09.005.

    Article  CAS  PubMed  Google Scholar 

  54. Stankoska K, Sarram L, Smith S, Bedran-Russo AK, Little CB, Swain MV, et al. Immunolocalization and distribution of proteoglycans in carious dentine. Aust Dent J. 2016;61(3):288–97. https://doi.org/10.1111/adj.12376.

    Article  CAS  PubMed  Google Scholar 

  55. Fonovic M, Turk B. Cysteine cathepsins and extracellular matrix degradation. Biochim Biophys Acta. 2014;1840(8):2560–70. https://doi.org/10.1016/j.bbagen.2014.03.017.

    Article  CAS  PubMed  Google Scholar 

  56. Aguda AH, Panwar P, Du X, Nguyen NT, Brayer GD, Bromme D. Structural basis of collagen fiber degradation by cathepsin K. Proc Natl Acad Sci U S A. 2014;111(49):17474–9. https://doi.org/10.1073/pnas.1414126111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Smith AJ, Scheven BA, Takahashi Y, Ferracane JL, Shelton RM, Cooper PR. Dentine as a bioactive extracellular matrix. Arch Oral Biol. 2012;57(2):109–21. https://doi.org/10.1016/j.archoralbio.2011.07.008.

    Article  CAS  PubMed  Google Scholar 

  58. He G, Dahl T, Veis A, George A. Nucleation of apatite crystals in vitro by self-assembled dentin matrix protein 1. Nat Mater. 2003;2(8):552–8. https://doi.org/10.1038/nmat945.

    Article  CAS  PubMed  Google Scholar 

  59. Baht GS, Hunter GK, Goldberg HA. Bone sialoprotein-collagen interaction promotes hydroxyapatite nucleation. Matrix Biol. 2008;27(7):600–8. https://doi.org/10.1016/j.matbio.2008.06.004.

    Article  CAS  PubMed  Google Scholar 

  60. Goldberg M, Septier D, Rapoport O, Iozzo RV, Young MF, Ameye LG. Targeted disruption of two small leucine-rich proteoglycans, biglycan and decorin, excerpts divergent effects on enamel and dentin formation. Calcif Tissue Int. 2005;77(5):297–310. https://doi.org/10.1007/s00223-005-0026-7.

    Article  CAS  PubMed  Google Scholar 

  61. Kalyva M, Papadimitriou S, Tziafas D. Transdentinal stimulation of tertiary dentine formation and intratubular mineralization by growth factors. Int Endod J. 2010;43(5):382–92. https://doi.org/10.1111/j.1365-2591.2010.01690.x.

    Article  CAS  PubMed  Google Scholar 

  62. Six N, Decup F, Lasfargues JJ, Salih E, Goldberg M. Osteogenic proteins (bone sialoprotein and bone morphogenetic protein-7) and dental pulp mineralization. J Mater Sci Mater Med. 2002;13(2):225–32. https://doi.org/10.1023/a:1013846516693.

    Article  CAS  PubMed  Google Scholar 

  63. Goldberg M, Six N, Decup F, Buch D, Soheili Majd E, Lasfargues JJ, et al. Application of bioactive molecules in pulp-capping situations. Adv Dent Res. 2001;15:91–5. https://doi.org/10.1177/08959374010150012401.

    Article  CAS  PubMed  Google Scholar 

  64. • Galler KM, Weber M, Korkmaz Y, Widbiller M, Feuerer M. Inflammatory response mechanisms of the dentine-pulp complex and the periapical tissues. Int J Mol Sci. 2021;22(3). https://doi.org/10.3390/ijms22031480. (Comprehensive review about inflammatory responses of the dentin-pulp complex including odontoblast response to bacterial by-products and formation of tertiary dentin. This review also discusses the healing mechanisms of the dental pulp and link between inflammation and repair.)

  65. Smith AJ, Cassidy N, Perry H, Begue-Kirn C, Ruch JV, Lesot H. Reactionary dentinogenesis. Int J Dev Biol. 1995;39(1):273–80.

    CAS  PubMed  Google Scholar 

  66. Wan CY, Li L, Liu LS, Jiang CM, Zhang HZ, Wang JX. Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases during apical periodontitis development. J Endod. 2021;47(7):1118–25. https://doi.org/10.1016/j.joen.2021.04.005.

    Article  PubMed  Google Scholar 

  67. Shin SJ, Lee JI, Baek SH, Lim SS. Tissue levels of matrix metalloproteinases in pulps and periapical lesions. J Endod. 2002;28(4):313–5. https://doi.org/10.1097/00004770-200204000-00013.

    Article  PubMed  Google Scholar 

  68. Gusman H, Santana RB, Zehnder M. Matrix metalloproteinase levels and gelatinolytic activity in clinically healthy and inflamed human dental pulps. Eur J Oral Sci. 2002;110(5):353–7. https://doi.org/10.1034/j.1600-0722.2002.21347.x.

    Article  CAS  PubMed  Google Scholar 

  69. Kritikou K, Greabu M, Imre M, Miricescu D, Ripszky Totan A, Burcea M, et al. ILs and MMPs levels in inflamed human dental pulp: a systematic review. Molecules. 2021;26(14). https://doi.org/10.3390/molecules26144129.

  70. Yu F, Huo F, Li F, Zuo Y, Wang C, Ye L. Aberrant NF-kappaB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption. Int J Oral Sci. 2022;14(1):6. https://doi.org/10.1038/s41368-022-00159-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Takimoto K, Kawashima N, Suzuki N, Koizumi Y, Yamamoto M, Nakashima M, et al. Down-regulation of inflammatory mediator synthesis and infiltration of inflammatory cells by MMP-3 in experimentally induced rat pulpitis. J Endod. 2014;40(9):1404–9. https://doi.org/10.1016/j.joen.2014.04.001.

    Article  PubMed  Google Scholar 

  72. Eba H, Murasawa Y, Iohara K, Isogai Z, Nakamura H, Nakamura H, et al. The anti-inflammatory effects of matrix metalloproteinase-3 on irreversible pulpitis of mature erupted teeth. PLoS One. 2012;7(12):e52523. https://doi.org/10.1371/journal.pone.0052523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zheng L, Amano K, Iohara K, Ito M, Imabayashi K, Into T, et al. Matrix metalloproteinase-3 accelerates wound healing following dental pulp injury. Am J Pathol. 2009;175(5):1905–14. https://doi.org/10.2353/ajpath.2009.080705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Manicone AM, McGuire JK. Matrix metalloproteinases as modulators of inflammation. Semin Cell Dev Biol. 2008;19(1):34–41. https://doi.org/10.1016/j.semcdb.2007.07.003.

    Article  CAS  PubMed  Google Scholar 

  75. •• Okamoto M, Takahashi Y, Komichi S, Cooper PR, Hayashi M. Dentinogenic effects of extracted dentin matrix components digested with matrix metalloproteinases. Sci Rep. 2018;8(1):10690. https://doi.org/10.1038/s41598-018-29112-3. (This in vivo and in vitro study reported the potential of dentin extracted proteins digested by MMPs to induce dental pulp stem cell proliferation and migration, improve the angiogenic and mineralization potential, and induce formation of tertiary dentin.)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Cooper PR, Takahashi Y, Graham LW, Simon S, Imazato S, Smith AJ. Inflammation-regeneration interplay in the dentine-pulp complex. J Dent. 2010;38(9):687–97. https://doi.org/10.1016/j.jdent.2010.05.016.

    Article  CAS  PubMed  Google Scholar 

  77. Farges JC, Alliot-Licht B, Renard E, Ducret M, Gaudin A, Smith AJ, et al. Dental pulp defence and repair mechanisms in dental caries. Mediators Inflamm. 2015;2015:230251. https://doi.org/10.1155/2015/230251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Komichi S, Takahashi Y, Okamoto M, Ali M, Watanabe M, Huang H, et al. Protein S100-A7 derived from digested dentin is a critical molecule for dentin pulp regeneration. Cells. 2019;8(9). https://doi.org/10.3390/cells8091002.

  79. Salehi S, Cooper P, Smith A, Ferracane J. Dentin matrix components extracted with phosphoric acid enhance cell proliferation and mineralization. Dent Mater. 2016;32(3):334–42. https://doi.org/10.1016/j.dental.2015.11.004.

    Article  CAS  PubMed  Google Scholar 

  80. Athirasala A, Tahayeri A, Thrivikraman G, Franca CM, Monteiro N, Tran V, et al. A dentin-derived hydrogel bioink for 3D bioprinting of cell laden scaffolds for regenerative dentistry. Biofabrication. 2018;10(2):024101. https://doi.org/10.1088/1758-5090/aa9b4e.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Tersariol IL, Geraldeli S, Minciotti CL, Nascimento FD, Paakkonen V, Martins MT, et al. Cysteine cathepsins in human dentin-pulp complex. J Endod. 2010;36(3):475–81. https://doi.org/10.1016/j.joen.2009.12.034.

    Article  PubMed  Google Scholar 

  82. Tatti O, Vehvilainen P, Lehti K, Keski-Oja J. MT1-MMP releases latent TGF-beta1 from endothelial cell extracellular matrix via proteolytic processing of LTBP-1. Exp Cell Res. 2008;314(13):2501–14. https://doi.org/10.1016/j.yexcr.2008.05.018.

    Article  CAS  PubMed  Google Scholar 

  83. Charadram N, Farahani RM, Harty D, Rathsam C, Swain MV, Hunter N. Regulation of reactionary dentin formation by odontoblasts in response to polymicrobial invasion of dentin matrix. Bone. 2012;50(1):265–75. https://doi.org/10.1016/j.bone.2011.10.031.

    Article  CAS  PubMed  Google Scholar 

  84. Tomson PL, Lumley PJ, Smith AJ, Cooper PR. Growth factor release from dentine matrix by pulp-capping agents promotes pulp tissue repair-associated events. Int Endod J. 2017;50(3):281–92. https://doi.org/10.1111/iej.12624.

    Article  CAS  PubMed  Google Scholar 

  85. Huang CC, Ravindran S, Kang M, Cooper LF, George A. Engineering a self-assembling leucine zipper hydrogel system with function-specific motifs for tissue regeneration. ACS Biomater Sci Eng. 2020;6(5):2913–28. https://doi.org/10.1021/acsbiomaterials.0c00026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zehnder M, Wegehaupt FJ, Attin T. A first study on the usefulness of matrix metalloproteinase 9 from dentinal fluid to indicate pulp inflammation. J Endod. 2011;37(1):17–20. https://doi.org/10.1016/j.joen.2010.10.003.

    Article  PubMed  Google Scholar 

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Funding

This work was supported by the National Institute of Dental and Craniofacial Research grant K08 DE029490 (Vidal).

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Vidal, C.M.P., Carrilho, M.R. Dentin Degradation: From Tissue Breakdown to Possibilities for Therapeutic Intervention. Curr Oral Health Rep 10, 99–110 (2023). https://doi.org/10.1007/s40496-023-00341-4

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