In Vivo Regulation of Active Matrix Metalloproteinase-8 (aMMP-8) in Periodontitis: From Transcriptomics to Real-Time Online Diagnostics and Treatment Monitoring
Nur Rahman Ahmad Seno Aji,
Tülay Yucel-Lindberg,
Ismo T. Räisänen,
Heidi Kuula,
Mikko T. Nieminen,
Maelíosa T. C. Mc Crudden,
Dyah Listyarifah,
Anna Lundmark,
Fionnuala T. Lundy,
Shipra Gupta,
Timo Sorsa
Affiliations
Nur Rahman Ahmad Seno Aji
Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
Tülay Yucel-Lindberg
Division of Pediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, 171 77 Huddinge, Sweden
Ismo T. Räisänen
Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
Heidi Kuula
Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
Mikko T. Nieminen
Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
Maelíosa T. C. Mc Crudden
Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine Dentistry and Biomedical Science, Queen’s University Belfast, Belfast BT9 7BL, UK
Dyah Listyarifah
Department of Dental Biomedical Sciences, Faculty of Dentistry, Universitas Gadjah Mada, Jl. Denta Sekip Utara No 1, Yogyakarta 55281, Indonesia
Anna Lundmark
Division of Pediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, 171 77 Huddinge, Sweden
Fionnuala T. Lundy
Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine Dentistry and Biomedical Science, Queen’s University Belfast, Belfast BT9 7BL, UK
Shipra Gupta
Oral Health Sciences Centre, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India
Timo Sorsa
Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
Background: This study investigated in vivo regulation and levels of active matrix metalloproteinase-8 (aMMP-8), a major collagenolytic protease, in periodontitis. Methods: Twenty-seven adults with chronic periodontitis (CP) and 30 periodontally healthy controls (HC) were enrolled in immunohistochemistry and transcriptomics analytics in order to assess Treponema denticola (Td) dentilisin and MMP-8 immunoexpression, mRNA expression of MMP-8 and its regulators (IL-1β, MMP-2, MMP-7, TIMP-1). Furthermore, the periodontal anti-infective treatment effect was monitored by four different MMP-8 assays (aMMP-8-IFMA, aMMP-8-Oralyzer, MMP-8-activity [RFU/minute], and total MMP-8 by ELISA) among 12 CP (compared to 25 HC). Results: Immunohistochemistry revealed significantly more Td-dentilisin and MMP-8 immunoreactivities in CP vs. HC. Transcriptomics revealed significantly elevated IL-1β and MMP-7 RNA expressions, and MMP-2 RNA was slightly reduced. No significant differences were recorded in the relatively low or barely detectable levels of MMP-8 mRNAs. Periodontal treatment significantly decreased all MMP-8 assay levels accompanied by the assessed clinical indices (periodontal probing depths, bleeding-on-probing, and visual plaque levels). However, active but not total MMP-8 levels persisted higher in CP than in periodontally healthy controls. Conclusion: In periodontal health, there are low aMMP-8 levels. The presence of Td-dentilisin in CP gingivae is associated with elevated aMMP-8 levels, potentially contributing to a higher risk of active periodontal tissue collagenolysis and progression of periodontitis. This can be detected by aMMP-8-specific assays and online/real-time aMMP-8 chair-side testing.
