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Active matrix metalloproteinase-8 and interleukin-6 detect periodontal degeneration caused by radiotherapy of head and neck cancer: a pilot study
Mutlu Keskin, Hanna Lahteenmaki, Nilminie Rathnayake, Ismo T. Raisanen, Taina Tervahartiala, Pirjo Parnanen, Ahmet Murat Şenışık, Didem Karaçetin, Ayben Yentek Balkanay, Pia Heikkila, Jaana Hagström, Jaana Rautava, Caj Haglund, Ulvi Kahraman Gursoy, Angelika Silbereisen, Nagihan Bostanci and Timo Sorsa
Abstract
Background: This cohort study investigated the role of the active matrix metalloproteinase-8 (aMMP-8) and interleukin-6 (IL-6) as oral fluid biomarkers for monitoring the periodontal degeneration occurring in head and neck cancer (HNC) patients treated by radiotherapy.
Research design and methods: Eleven patients, aged 28–74, diagnosed with HNC were included in the study. Complete periodontal and oral examinations were performed pre-radiotherapy and 1 month after radiotherapy. Mouthrinse samples (pre-radiotherapy, after 6 weeks of radiotherapy and 1 month after radiotherapy) were assayed by aMMP-8 point-of-care-kit (PerioSafe./ORALyzer.) for aMMP-8 and ELISA for IL-6.
Results: HNC radiotherapy had a deteriorating impact on the periodontium and a significant impact on periodontal biomarkers aMMP-8 and IL-6 and increased their levels in mouthrinse. Clinical-attachmentloss (CAL) (site of greatest loss: mean = 1.7 mm, range = 1–3 mm) corresponding to rapid progression of periodontitis. There was a positive repeated measures correlation (rmcorr = 0.667) between the aMMP-8 and IL-6 levels.
Conclusions: Elevated aMMP-8 levels were observed 1 month after radiotherapy among some HNC patients suggesting a prolonged increased susceptibility to further periodontal tissue destruction. Currently available aMMP-8 point-of-care testing could be useful to monitor and assess quantitatively online and real-time the risk of deterioration of periodontal health during HNC radiotherapy.
Effects of Lactobacillus reuteri PTA 5289 and L. paracasei DSMZ16671 on the adhesion and biofilm formation of Streptococcus mutans
Aino M Marttinen , Anna L Haukioja, Mutlu Keskin, Eva M Söderling
Abstract
Probiotics have decreased the counts of salivary mutans streptococci (MS) in clinical studies. The aim of this study was to compare the effects of Lactobacillus reuteri PTA 5289 and L. paracasei DSMZ16671 on the adhesion of a reference strain and a clinical isolate of Streptococcus mutans and on the counts of MS in a biofilm. The adhesion of S. mutans Ingbritt and the clinical isolate S. mutans 2366 to a smooth glass surface and saliva-coated hydroxyapatite (SHA) were studied in the presence of and without the lactobacilli. A three-species biofilm formed on saliva-coated hydroxyapatite discs was used in the biofilm experiments. The lactobacilli did not affect adhesion to the glass surface but interfered with binding to SHA. No effects of the lactobacilli were detected on the MS levels in the three-species biofilms. The results of the SHA binding experiments best reflected the results of the existing clinical studies.
A Comparative Analysis of Biofilm Characteristics of Dual-Species Periodontopathogenic Biofilm based on Fusobacterium nucleatum and the Dual- Species Biofilm Response in the Presence of Antimicrobial Peptide
Abstract: Fusobacterium nucleatum (F.nucleatum), which acts as a linking periodontopathogenic bacteria, has the
ability of coaggregation with early and late colonization species. It is the most intense gram-negative bacteria found
in periodontal health and increases in periodontal diseased areas numerically. In this study, comparative analyses of dual
and mono-biofilm structural characteristics formed by Porphyromonas gingivalis and Prevotella intermedia with F.
nucleatum have been evaluated. In all results, more biofilm formation was observed in dual-species compared to monospecies
biofilms. Biofilm formation of F. nucleatum-P.intermedia has increased in the presence of Human Neutrophilic
Peptide (HNP-1). In this study it is concluded that dual-periodontopathogenic coaggregations based on F. nucleatum
could produce more intense biofilm structure than single-species ones, and the increase in dual-species biofilm
mass in the presence of low doses of HNP-1 may be a defense mechanism of dual periodontopathogenic biofilm.
Keskin M, Könönen E, Söderling E, Isik G, Firatli E, Uitto VJ, Gürsoy UK.
Abstract: Human neutrophilic peptides (HNPs) constitute a class of host defense molecules, which contribute to the non-oxidative killing of bacteria and other microorganisms. Since the adaptability is crucial to bacterial survival in changing environments, it is of interest to know how Fusobacterium nucleatum, the major bridge organism connecting early and late colonizers in dental biofilms, defends itself against HNPs. This study aimed to examine the planktonic growth, membrane permeability, and biofilm formation characteristics as defense mechanisms of F. nucleatum against HNP-1. In all experiments, the type strain of F. nucleatum (ssp. nucleatum ATCC 25586) and two clinical strains (ssp. nucleatum AHN 9508 and ssp. polymorphum AHN 9910) were used. Planktonic growth (measured in colony forming units), capsular polysaccharide production (visualized by Ziehl-Neelsen stain), membrane permeability (demonstrated as N-phenyl-1-naphthylamine uptake), biofilm formation, and established biofilm development (measured as total mass and polysaccharide levels) were analyzed in the presence of 0 μg/ml (control), 1 μg/ml, 5 μg/ml, and 10 μg/ml of HNP-1. Planktonic growth of the strains AHN 9508 and ATCC 25586 were significantly (p<0.05) increased in the presence of HNP-1, while their membrane permeability decreased (p<0.005) in the planktonic form. HNP-1 decreased the biofilm formation of the strains ATCC 25586 and AHN 9910, whereas it increased the growth of the strain AHN 9508 in established biofilms. Capsule formation and polysaccharide production were not observed in any strain. We conclude that the inhibition of the membrane permeability and the increase in planktonic and established biofilm growth could act as bacterial defense mechanisms against neutrophilic defensins. In addition, this strain-dependent survival ability against HNP-1 may explain the variation in the virulence of different F. nucleatum strains.
Keskin M, Zeidán-Chuliá F, Gursoy M, Könönen E, Rautava J, Gursoy UK.
Abstract: Recent advances in multi-omics approaches encompassing genomics, transcriptomics, proteomics, and metabolomics offer hitherto unprecedented insights on common complex human diseases. A unique angle pertinent for both diagnostic and therapeutic sciences involves rethinking clinically distinct diseases with a view to their shared molecular targets, interactomes, and pathophysiologies. Reflecting at a scale of disease-to-disease associations might help clinicians, public health practitioners, drug and biotechnology developers, and associated knowledge industries in the current era. This review article examines the hypothesis that "Intersecting Molecular Pathways Permit Interventions on Multiple Clinical Endpoints", thus uniquely bringing together Crohn's disease and periodontitis. Furthermore, we propose a novel connector molecular target between these two ostensibly distinct diseases at a clinical level, human beta defensin (hBD)-2, and suggest pathways by which hBD-2 can conceivably connect Crohn's disease and periodontitis by virtue of regulating the innate-immune response. We conclude by emphasizing different approaches where hBD-2 can be employed as a diagnostic and therapeutic tool to improve the quality of life of susceptible individuals and minimize the economic costs of these two major global public health problems. The strategy presented here also presents potentials for targeting of multiple diseases through a unique "nodal molecular target" that "speaks to" multiple clinical endpoints.
Zeidán-Chuliá F, Keskin M, Könönen E, Uitto VJ, Söderling E, Moreira JC, Gürsoy UK.
Abstract: The present report examined the effects of essential oils (EOs) from Satureja hortensis L. and Salvia fruticosa M. on the viability and outer membrane permeability of the periodontopathogen Fusobacterium nucleatum, a key bacteria in oral biofilms, as well as the inhibition of matrix metalloproteinase (MMP-2 and MMP-9) activities in epithelial cells exposed to such bacteria. Membrane permeability was tested by measuring the N-phenyl-1-naphthylamine uptake and bacterial viability by using the commercially available Live/Dead BacLight kit. In addition, gelatin zymography was performed to analyze the inhibition of F. nucleatum-induced MMP-2 and MMP-9 activities in HaCaT cells. We showed that 5, 10, and 25 μL/mL of Sat. hortensis L. EO decreased the ratio of live/dead bacteria and increased the outer membrane permeability in a range of time from 0 to 5 min. Treatments with 10 and 25 μL/mL of Sal. fruticosa M. also increased the membrane permeability and 5, 10, and 25 μL/mL of both EOs inhibited MMP-2 and MMP-9 activities in keratinocytes induced after exposure of 24 h to F. nucleatum. We conclude that antibacterial and antigelatinolytic activities of Sat. hortensis L. EO have potential for the treatment of periodontal inflammation.