Postradiation Matrix Metalloproteinase-20 Expression and Its Impact on Dental Micromorphology and Radiation-Related Caries

Abstract

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.

Radiation-related caries assessment through the International Caries Detection and Assessment System and the Post-Radiation Dental Index

“…This result corroborates those of previous works suggesting that both the direct effects of HNRT and the clustering of oral symptoms caused by the treatment, especially the reduction of the salivary flow, have an important role in the onset and progression of RRC. 7,[19][20][21] In our study, the median time for RRC onset was 11.5 months, which is consistent with that reported in the literature, which describes the appearance of RRC after a period of approximately 12 months following the conclusion of HNRT. 3,22 Most of our cases were diagnosed as advanced RRC lesions; the reason may be patients' failure to comply with dental follow-up after the onco-logic treatment was completed.…”

“…This axial/transversal progression seen in our sample indicates that the "strangulation" process that leads to crown amputation is the most advanced stage of RRC in terms of structure loss. 5,11,20,28,29 Remarkably, the results of our study revealed high scores for both the ICDAS and the PRDI, reinforcing the fact that RRC lesions are mainly diagnosed in late stages and, therefore, are identified when there is already severe tooth destruction. The ICDAS severity in our sample is not compatible with that reported in previous works that assessed conventional caries for an epidemiologic purpose and presented a higher prevalence of initial scores.…”

“…The difficulty in the identification of incipient clinical manifestations of RRC and the consequent late diagnosis may be the basis for the well-known low rate of success for restorative treatment protocols in RRC. [4][5][6]20,31…”

Radiotherapy Activates and Protease Inhibitors Inactivate Matrix Metalloproteinases in the Dentinoenamel Junction of Permanent Teeth

“…These results indicate a possible molecular mechanism underlying the rapid onset and progression of radiationinduced caries. Contrarily, in recent studies, these direct effects of radiation were not observed, with no evident differences in the expression and activity of MMP-2 and MMP-9 in the DEJ and dentin-pulp complex of irradiated teeth [Gomes-Silva et al, 2017b], and MMP-20 overexpression not factored into analysis in these groups of teeth [Gomes-Silva et al, 2017a]. While these studies used teeth extracted from patients who had undergone radiotherapy, our study used teeth submitted to the radiation protocol after extraction.…”

The impact of head and neck radiotherapy on the dentine-enamel junction: a systematic review

“…Clinical research suggests that the mechanical properties of the enamel are negatively affected by HNRT; however, no consensus has been established in the literature concerning the ability of ionising radiation to be directly injurious to the DEJ, increasing the risk for enamel delamination and RRC progression (15)(16)(17). Despite controversial results regarding radiation-related damage to the DEJ microstructure in HNC patients (4,10,18), many studies aimed to evaluate that enzymatic expression favours RRC progression (9,15,19,20). Therefore, this systematic review aimed to evaluate if HNRT should be considered an independent risk factor to damage the physicochemical properties of the DEJ in cancer patients.…”