Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study
The effect of head and neck cancer (HNC) radiotherapy (RT) on biomarkers is not known but there is a lot of potential for gaining more precise cancer treatments and less side effects. This cohort study investigated the levels and molecular forms of the matrix metalloproteinase (MMP) -8 and -9, tissu...
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MDPI AG
2023-12-01
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| author | Ella Brandt Mutlu Keskin Ismo T. Räisänen Taina Tervahartiala Antti Mäkitie İlknur Harmankaya Didem Karaçetin Jaana Hagström Jaana Rautava Timo Sorsa |
| author_facet | Ella Brandt Mutlu Keskin Ismo T. Räisänen Taina Tervahartiala Antti Mäkitie İlknur Harmankaya Didem Karaçetin Jaana Hagström Jaana Rautava Timo Sorsa |
| author_sort | Ella Brandt |
| collection | DOAJ |
| description | The effect of head and neck cancer (HNC) radiotherapy (RT) on biomarkers is not known but there is a lot of potential for gaining more precise cancer treatments and less side effects. This cohort study investigated the levels and molecular forms of the matrix metalloproteinase (MMP) -8 and -9, tissue inhibitor of metalloproteinase (TIMP)-1, myeloperoxidase (MPO) and interleukin (IL)-6 in mouth-rinse samples as well as the clinical periodontal status in HNC patients (<i>n</i> = 21) receiving RT. Complete periodontal examinations were performed pre-RT and one month after RT. Mouth-rinse samples (pre-RT, after six weeks of RT and one month after RT) were assayed using a point-of-care-kit (PerioSafe<sup>®</sup>/ORALyzer<sup>®</sup> (Dentognostics GmbH, Jena, Germany)) for active MMP-8 and ELISA analysis for total MMP-8 and -9, MPO, TIMP-1, and IL-6 levels. Molecular forms of MMP-9 were assessed by gelatinolytic zymography and MMP-8 by western immunoblot. Significant changes were observed between the three time points in the mean levels of active and total MMP-8, active MMP-9, and IL-6. Their levels increased during the RT and decreased after the RT period. The aMMP-8 levels stayed elevated even one month after RT compared to the pre-RT. Clinical attachment loss, probing depths, and bleeding on probing were increased between pre- and post-calculations in periodontal status. Elevated inflammatory biomarker levels together with clinical recordings strongly suggest that RT eventually increases the risk to the periodontal tissue destruction by inducing the active proteolytical MMP-cascade, and especially by prolonged activity of collagenolytic aMMP-8. Eventually, the aMMP-8 point-of-care mouth-rinse test could be an easy, early detection tool for estimating the risk for periodontal damage by the destructive MMP-cascade in HNC patients with RT treatment. |
| first_indexed | 2024-03-08T09:57:32Z |
| format | Article |
| id | doaj.art-2114db8d3f734c2c8a9d8796298e3370 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T09:57:32Z |
| publishDate | 2023-12-01 |
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| series | Biomedicines |
| spelling | doaj.art-2114db8d3f734c2c8a9d8796298e33702024-01-29T13:46:37ZengMDPI AGBiomedicines2227-90592023-12-011212710.3390/biomedicines12010027Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort StudyElla Brandt0Mutlu Keskin1Ismo T. Räisänen2Taina Tervahartiala3Antti Mäkitie4İlknur Harmankaya5Didem Karaçetin6Jaana Hagström7Jaana Rautava8Timo Sorsa9Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, FinlandOral and Dental Health Department, Altınbaş University, 34147 Istanbul, TurkeyDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, FinlandDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, FinlandDepartment of Otorhinolaryngology—Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00029 Helsinki, FinlandDepartment of Radiation Oncology, Başakşehir Çam and Sakura City Hospital, 34480 Istanbul, TurkeyDepartment of Radiation Oncology, Başakşehir Çam and Sakura City Hospital, 34480 Istanbul, TurkeyDepartment of Pathology, Helsinki University Hospital, 00014 Helsinki, FinlandDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, FinlandDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, FinlandThe effect of head and neck cancer (HNC) radiotherapy (RT) on biomarkers is not known but there is a lot of potential for gaining more precise cancer treatments and less side effects. This cohort study investigated the levels and molecular forms of the matrix metalloproteinase (MMP) -8 and -9, tissue inhibitor of metalloproteinase (TIMP)-1, myeloperoxidase (MPO) and interleukin (IL)-6 in mouth-rinse samples as well as the clinical periodontal status in HNC patients (<i>n</i> = 21) receiving RT. Complete periodontal examinations were performed pre-RT and one month after RT. Mouth-rinse samples (pre-RT, after six weeks of RT and one month after RT) were assayed using a point-of-care-kit (PerioSafe<sup>®</sup>/ORALyzer<sup>®</sup> (Dentognostics GmbH, Jena, Germany)) for active MMP-8 and ELISA analysis for total MMP-8 and -9, MPO, TIMP-1, and IL-6 levels. Molecular forms of MMP-9 were assessed by gelatinolytic zymography and MMP-8 by western immunoblot. Significant changes were observed between the three time points in the mean levels of active and total MMP-8, active MMP-9, and IL-6. Their levels increased during the RT and decreased after the RT period. The aMMP-8 levels stayed elevated even one month after RT compared to the pre-RT. Clinical attachment loss, probing depths, and bleeding on probing were increased between pre- and post-calculations in periodontal status. Elevated inflammatory biomarker levels together with clinical recordings strongly suggest that RT eventually increases the risk to the periodontal tissue destruction by inducing the active proteolytical MMP-cascade, and especially by prolonged activity of collagenolytic aMMP-8. Eventually, the aMMP-8 point-of-care mouth-rinse test could be an easy, early detection tool for estimating the risk for periodontal damage by the destructive MMP-cascade in HNC patients with RT treatment.https://www.mdpi.com/2227-9059/12/1/27head and neck cancerradiotherapybiomarkermatrix metalloproteinaseaMMP-8periodontitis |
| spellingShingle | Ella Brandt Mutlu Keskin Ismo T. Räisänen Taina Tervahartiala Antti Mäkitie İlknur Harmankaya Didem Karaçetin Jaana Hagström Jaana Rautava Timo Sorsa Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study Biomedicines head and neck cancer radiotherapy biomarker matrix metalloproteinase aMMP-8 periodontitis |
| title | Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study |
| title_full | Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study |
| title_fullStr | Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study |
| title_full_unstemmed | Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study |
| title_short | Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study |
| title_sort | induction of collagenolytic mmp 8 and 9 tissue destruction cascade in mouth by head and neck cancer radiotherapy a cohort study |
| topic | head and neck cancer radiotherapy biomarker matrix metalloproteinase aMMP-8 periodontitis |
| url | https://www.mdpi.com/2227-9059/12/1/27 |
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