Brandt Ella, Kaman Wendy, Bikker Floris, Räisänen Ismo T, Mäkitie Antti, Keskin Mutlu, Karaçetin Didem, Hagström Jaana, Rautava Jaana, Sorsa Timo
Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Finland.
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Netherlands.
Cancer Control. 2025 Jan-Dec;32:10732748251351419. doi: 10.1177/10732748251351419. Epub 2025 Jun 22.
IntroductionMatrix metalloproteinases (MMP)-8 and -9 are regarded as biomarkers for periodontitis. The impact of head and neck carcinoma (HNC) radiotherapy (RT) on these biomarkers remains largely unexplored. This study aims to evaluate the impact of HNC RT on the proteases from host and bacteria, and their associations with the progression of periodontitis.MethodsTwenty-one patients with HNC receiving RT were included in this study. Mouthrinse samples were collected before RT (T0) and at the end of RT (T1). Periodontal examinations were conducted at T0 and one month after RT (T2). Samples were analyzed using a point-of-care kit for active (a) MMP-8, and ELISA for total (t) MMP-8, MMP-9, and interleukin (IL)-6 levels. Molecular forms of MMP-9 were assessed by gelatinolytic zymography. The activity levels of bacterial proteases, gingipain from and dentilisin from , were assayed by using Fluorescence Resonance Energy Transfer (FRET) peptide substrates. Modified cumulative risk score (CRS) index was used for combinatory biomarker analysis. We evaluated the impact of RT on biomarker concentrations as well as their associations with the mean clinical attachment loss (CAL) development, categorized as either progressive (CAL ≥0.1 mm) or low/no progression (CAL <0.1 mm).ResultsAll patients suffered from periodontitis. There were significant increases in the levels of aMMP-8, tMMP-8, aMMP-9, as well as in four modified CRS-indices due to RT ( < 0.05), but no impact on the activities of gingipain ( = 0.365) or dentilisin ( = 0.620). The mean levels of aMMP-8 and tMMP-9 were associated with CAL progression ( = 0.044, = 0.029, respectively).ConclusionHNC RT may result in the progression of periodontitis by increased activities of MMP-8 and -9. It seems that HNC RT has little impact on the activities of the bacteria-derived proteases dentilisin and gingipain.
引言
基质金属蛋白酶(MMP)-8和-9被视为牙周炎的生物标志物。头颈部癌(HNC)放疗(RT)对这些生物标志物的影响在很大程度上仍未得到探索。本研究旨在评估HNC放疗对宿主和细菌蛋白酶的影响,以及它们与牙周炎进展的关联。
方法
本研究纳入了21例接受放疗的HNC患者。在放疗前(T0)和放疗结束时(T1)收集漱口水样本。在T0和放疗后1个月(T2)进行牙周检查。使用即时检测试剂盒分析样本中活性(a)MMP-8的水平,采用酶联免疫吸附测定法(ELISA)检测总(t)MMP-8、MMP-9和白细胞介素(IL)-6的水平。通过明胶酶解酶谱法评估MMP-9的分子形式。使用荧光共振能量转移(FRET)肽底物检测细菌蛋白酶牙龈蛋白酶和牙本质素的活性水平。采用改良累积风险评分(CRS)指数进行联合生物标志物分析。我们评估了放疗对生物标志物浓度的影响,以及它们与平均临床附着丧失(CAL)进展的关联,CAL进展分为进展性(CAL≥0.1mm)或低/无进展(CAL<0.1mm)。
结果
所有患者均患有牙周炎。放疗后,aMMP-8、tMMP-8、aMMP-9水平以及四个改良CRS指数均显著升高(P<0.05),但对牙龈蛋白酶(P=0.365)或牙本质素(P=0.620)的活性没有影响。aMMP-8和tMMP-9的平均水平与CAL进展相关(分别为P=0.044和P=0.029)。
结论
HNC放疗可能通过增加MMP-8和-9的活性导致牙周炎进展。HNC放疗似乎对细菌来源蛋白酶牙本质素和牙龈蛋白酶的活性影响较小。