Recent evidence suggests that head-and-neck radiotherapy (HNRT) increases active forms of matrix metalloproteinase-20 (MMP-20) in human tooth crowns, degrading the dentin-enamel junction (DEJ) and leading to enamel delamination, which is a pivotal step in the formation of radiation-related caries (RRC). Additional participation of enzymatic degradation of organic matrix components in caries progression was attributed to MMP-20 in dentin. Therefore, the current study tested the hypothesis that MMP-20 is overexpressed in the DEJ, dentin-pulp complex components, and carious dentin of post-HNRT patients, leading to detectable micromorphological changes to the enamel and dentin. Thirty-six teeth were studied, including 19 post-HNRT specimens and 17 nonirradiated controls. Optical light microscopy was used to investigate the micromorphological components of the DEJ, dentin-pulp complex components, and carious dentin. The samples were divided into 2 subgroups: nondemineralized ground sections (n = 20) and demineralized histological sections (n = 16). In addition, immunohistochemical analysis using the immunoperoxidase technique was conducted to semiquantitatively assess MMP-20 expression in the DEJ, dentin-pulp complex components, and carious dentin. No apparent damage to the DEJ microstructure or other dentin-pulp complex components was observed and no statistically significant differences were detected in MMP-20 expression (p > 0.05) between the irradiated and control groups. This study rejected the hypothesis that MMP-20 is overexpressed in the DEJ, dentin-pulp complex components, and carious dentin of post-HNRT patients, leading to detectable micromorphological changes. Hence, direct effects of radiation may not be regarded as an independent factor to explain aggressive clinical patterns of RRC.

Keywords:
Caries, Dental tissues, Matrix metalloproteinase-20, Radiotherapy, Dentin-enamel junction, Head-and-neck cancer
1.
Argiris A, Karamouzis MV, Raben D, Ferris RL: Head and neck cancer. Lancet 2008;371:1695-1709.
2.
Buzalaf MA, Charone S, Tjäderhane L: Role of host-derived proteinases in dentine caries and erosion. Caries Res 2015;49(suppl 1):30-37.
3.
Caterina JJ, Skobe Z, Shi J, Ding Y, Simmer JP, Birkedal-Hansen H, Bartlett JD: Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype. J Biol Chem 2002;277:49598-49604.
4.
El-Faramawy N, Ameen R, El-Haddad K, El-Zainy M: Effects of gamma radiation on hard dental tissues of albino rats: investigation by light microscopy. Radiat Environ Biophys 2013;52:375-387.
5.
Faria KM, Brandão TB, Ribeiro AC, Vasconcellos AF, de Carvalho IT, de Arruda FF, Castro Junior G, Gross VC, Almeida OP, Lopes MA, Santos-Silva AR: Micromorphology of the dental pulp is highly preserved in cancer patients who underwent head and neck radiotherapy. J Endod 2014;40:1553-1559.
6.
Fränzel W, Gerlach R, Hein HJ, Schaller HG: Effect of tumour therapeutic irradiation on the mechanical properties of teeth tissue. Z Med Phys 2006;16:148-154.
7.
Fusayama T: Two layers of carious dentin; diagnosis and treatment. Oper Dent 1997;4:63-70.
8.
Galetti R, Santos-Silva AR, Antunes A, Alves FA, Lopes MA, Goes MF: Radiotherapy does not impair dentin adhesive properties in head and neck cancer patients. Clin Oral Invest 2014;18:1771-1778.
9.
Grötz KA, Duschner H, Kutzner J, Thelen M, Wagner W: New evidence for the etiology of the so-called radiation caries: proof for directed radiogenic damage od the enamel-dentin junction. Strahlenther Onkol 1997;173:668-676.
10.
Hong CH, Napeñas JJ, Hodgson BD, Stokman MA, Mathers-Stauffer V, Elting LS, Spijkervet FK, Brennan MT: A systematic review of dental disease in patients undergoing cancer therapy. Support Care Cancer 2010;18:1007-1021.
11.
Jansma J, Vissink A, Jongebloed WL, Retief DH, Johannes's-Gravenmade E: Natural and induced radiation caries: a SEM study. Am J Dent 1993;6:130-136.
12.
Kielbassa AM, Hinkelbein W, Hellwig E, Meyer-Lueckel H: Radiation-related damage to dentition. Lancet Oncol 2006;7:326-335.
13.
Kielbassa AM, Muntz I, Bruggmoser G, Schulte-Mönting J: Effect of demineralization and remineralization on microhardness of irradiated dentin. J Clin Dent 2002;13:104-110.
14.
Lee WH, Warrington JP, Sonntag WE, Lee YW: Irradiation alters MMP-2/TIMP-2 system and collagen type IV degradation in brain. Int J Radiation Oncol Biol Phys 2012;82:1559-1566.
15.
Lieshout HF, Bots CP: The effect of radiotherapy on dental hard tissues: a systematic review. Clin Oral Investig 2014;18:17-24.
16.
Llano E, Pendás AM, Knäuper V, Sorsa T, Salo T, Salido E, Murphy G, Simmer JP, Bartlett JD, López-Otín C: Identification and structural and functional characterization of human enamelysin (MMP-20). Biochemistry 1997;36:15101-15108.
17.
Matzinger O, Zouhair A, Mirimanoff RO, Ozsahin M: Radiochemotherapy in locally advanced squamous cell carcinomas of the head and neck. Clin Oncol 2009;21:525-531.
18.
Mazzoni A, Breschi L, Carrilho M, Nascimento FD, Orsini G, Ruggeri A, Gobbi P, Mazzotti G, Tay FR, Pashley DH, Tjäderhane L: A review on nature, role and functions of dentin non-collagenous proteins. 2. Enzymes, serum proteins and growth factors. Endod Topics 2012;21:19-40.
19.
McGuire JD, Mousa AA, Zhang BJ, Todoki LS, Huffman NT, Chandrababu KB, Moradian-Oldak J, Keightley A, Wang Y, Walker MP, Gorski JP: Extracts of irradiated mature human tooth crowns contain MMP-20 protein and activity. J Dent 2014a;42:626-635.
20.
McGuire JD, Walker MP, Dusevich V, Wang Y, Gorski JP: Enamel organic matrix: potential structural role in enamel and relationship to residual basement membrane constituents at the dentin enamel junction. Connect Tissue Res 2014b;55(suppl 1):33-37.
21.
Napeñas JJ, Rouleau TS: Oral complications of Sjögren's syndrome. Oral Maxillofac Surg Clin North Am 2014;26:55-62.
22.
Pioch T, Gofels D, Staehle HJ: An experimental study of the stability of irradiated teeth in the region of the dento-enamel junction. Endod Dent Traumatol 1992;8:241-244.
23.
Santos-Silva AR, Feio PDSQ, Vargas PA, Correa MEP, Lopes MA: cGVHD-related caries and its shared features with other ‘dry-mouth'-related caries. Braz Dent J 2015;26:435-440.
24.
Sciubba JJ, Goldenberg D: Oral complications of radiotherapy. Lancet Oncol 2006;7:175-183.
25.
Silva AR, Alves FA, Antunes A, Goes MF, Lopes MA: Patterns of demineralization and dentin reactions in radiation-related caries. Caries Res 2009;43:43-49.
26.
Silva AR, Alves FA, Berger SB, Giannini M, Goes MF, Lopes MA: Radiation-related caries and early restoration failure in head and neck cancer patients: a polarized light microscopy and scanning electron microscopy study. Support Care Cancer 2010;18:83-87.
27.
Springer IN, Niehoff P, Warnke PH, Bocek G, Kovacs G, Suhr M, Wiltfang J, Açil Y: Radiation caries: radiogenic destruction of dental collagen. Oral Oncol 2005;41:723-728.
28.
Sulkala M, Larmas M, Sorsa T, Salo T, Tjäderhane L: The localization of matrix metalloproteinase-20 (MMP-20, enamelysin) in mature human teeth. J Dent Res 2002;81:603-607.
29.
Tjäderhane L, Buzalaf MAR, Carrilho M, Chaussain C: Matrix metalloproteinases and other matrix proteinases in relation to cariology: the era of “dentin degradomics”. Caries Res 2015;49:193-208.
30.
Tjäderhane 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;77:1622-1629.
31.
Turk BE, Lee DH, Yamakoshi Y, Klingenhoff A, Reichenberger E, Wright JT, Simmer JP, Komisarof JA, Cantley LC, Bartlett JD: MMP-20 is predominately a tooth-specific enzyme with a deep catalytic pocket that hydrolyzes type V collagen. Biochemistry 2006;45:3863-3874.
32.
van Strijp AJ, Jansen DC, DeGroot J, Ten Cate JM, Everts V: Host-derived proteinases and degradation of dentine collagen in situ. Caries Res 2003;37:v58-v65.
33.
Vidal CM, Tjäderhane L, Scaffa PM, Tersariol IL, Pashley DH, Nader HB, Nascimento FD, Carrilho MR: Abundance of MMPs and cysteine-cathepsins in carious dentin. J Dent Res 2014;93:269-274.
34.
Walker MP, Wichman B, Cheng AL, Coster J, Williams KB: Impact of radiotherapy dose on dentition breakdown in head and neck cancer patients. Pract Radiat Oncol 2011;1:142-148.
35.
Walker MP, Williams KB, Wichman B: Post-radiation dental index: development and reliability. Support Care Cancer 2008;16:525-530.
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