aMMP-8 and MMP-9: Potential Biomarkers for periodontitis Progression in Patients Receiving Radiotherapy for Head and Neck Carcinoma

Ella Brandt; Wendy Kaman; Floris Bikker; Ismo T. Räisänen; Antti Mäkitie; Mutlu Keskin; Didem Karaçetin; Jaana Hagström; Jaana Rautava; Timo Sorsa

doi:10.1177/10732748251351419

aMMP-8 and MMP-9: Potential Biomarkers for periodontitis Progression in Patients Receiving Radiotherapy for Head and Neck Carcinoma

Ella Brandt
, Wendy Kaman
, Floris Bikker
, Ismo T. Räisänen
, Antti Mäkitie
, Mutlu Keskin
, Didem Karaçetin
, Jaana Hagström
, Jaana Rautava
, Timo Sorsa

Oral Biochemistry

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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 Porphyromonas gingivalis and dentilisin from Treponema denticola, 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 (P < 0.05), but no impact on the activities of gingipain (P = 0.365) or dentilisin (P = 0.620). The mean levels of aMMP-8 and tMMP-9 were associated with CAL progression (P = 0.044, P = 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.

Original language	English
Article number	10732748251351419
Pages (from-to)	1-11
Number of pages	11
Journal	Cancer Control
Volume	32
Early online date	22 Jun 2025
DOIs	https://doi.org/10.1177/10732748251351419
Publication status	Published - Jul 2025

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by the Helsinki and Uusimaa Hospital District (HUS), Finland (grant number TYH2020337, TYH2022225, Y2519SU010), the Finnish Dental Association Apollonia, Finland, and Karolinska Institutet, Sweden, and Finnish Dental Accociation (to E.B). Open access funding was provided by Helsinki University Library, University of Helsinki. This research did not received grants from any funding agency in the commercial sector. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Funders	Funder number
Helsingin Yliopisto
Finnish Dental Accociation
Karolinska Institutet
Suomen Hammaslääkäriliitto
Helsinki and Uusimaa Hospital District	TYH2022225, TYH2020337, Y2519SU010

Keywords

biomarker
head and neck carcinoma
matrix metalloproteinase
periodontitis
radiotherapy

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Brandt, E., Kaman, W., Bikker, F., Räisänen, I. T., Mäkitie, A., Keskin, M., Karaçetin, D., Hagström, J., Rautava, J., & Sorsa, T. (2025). aMMP-8 and MMP-9: Potential Biomarkers for periodontitis Progression in Patients Receiving Radiotherapy for Head and Neck Carcinoma. Cancer Control, 32, 1-11. Article 10732748251351419. https://doi.org/10.1177/10732748251351419

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title = "aMMP-8 and MMP-9: Potential Biomarkers for periodontitis Progression in Patients Receiving Radiotherapy for Head and Neck Carcinoma",

abstract = "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 Porphyromonas gingivalis and dentilisin from Treponema denticola, 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 (P < 0.05), but no impact on the activities of gingipain (P = 0.365) or dentilisin (P = 0.620). The mean levels of aMMP-8 and tMMP-9 were associated with CAL progression (P = 0.044, P = 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.",

keywords = "biomarker, head and neck carcinoma, matrix metalloproteinase, periodontitis, radiotherapy",

author = "Ella Brandt and Wendy Kaman and Floris Bikker and R{\"a}is{\"a}nen, \{Ismo T.\} and Antti M{\"a}kitie and Mutlu Keskin and Didem Kara{\c c}etin and Jaana Hagstr{\"o}m and Jaana Rautava and Timo Sorsa",

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doi = "10.1177/10732748251351419",

language = "English",

volume = "32",

pages = "1--11",

journal = "Cancer Control",

issn = "1073-2748",

publisher = "SAGE Publications Ltd",

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T1 - aMMP-8 and MMP-9: Potential Biomarkers for periodontitis Progression in Patients Receiving Radiotherapy for Head and Neck Carcinoma

AU - Brandt, Ella

AU - Kaman, Wendy

AU - Bikker, Floris

AU - Räisänen, Ismo T.

AU - Mäkitie, Antti

AU - Keskin, Mutlu

AU - Karaçetin, Didem

AU - Hagström, Jaana

AU - Rautava, Jaana

AU - Sorsa, Timo

PY - 2025/7

Y1 - 2025/7

N2 - 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 Porphyromonas gingivalis and dentilisin from Treponema denticola, 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 (P < 0.05), but no impact on the activities of gingipain (P = 0.365) or dentilisin (P = 0.620). The mean levels of aMMP-8 and tMMP-9 were associated with CAL progression (P = 0.044, P = 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.

AB - 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 Porphyromonas gingivalis and dentilisin from Treponema denticola, 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 (P < 0.05), but no impact on the activities of gingipain (P = 0.365) or dentilisin (P = 0.620). The mean levels of aMMP-8 and tMMP-9 were associated with CAL progression (P = 0.044, P = 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.

KW - biomarker

KW - head and neck carcinoma

KW - matrix metalloproteinase

KW - periodontitis

KW - radiotherapy

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DO - 10.1177/10732748251351419

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aMMP-8 and MMP-9: Potential Biomarkers for periodontitis Progression in Patients Receiving Radiotherapy for Head and Neck Carcinoma

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