Browsing by Subject "MMP-8"

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  • Räisänen, Ismo T.; Heikkinen, Anna Maria; Pakbaznejad Esmaeili, Elmira; Tervahartiala, Taina; Pajukanta, Riitta; Silbereisen, Angelika; Bostanci, Nagihan; Sorsa, Timo (2019)
    Background This cross-sectional study aims to investigate if a point-of-care (PoC) test of active matrix metalloproteinase-8 (aMMP-8) predicts levels of inflammation amplifier triggering receptor expressed on myeloid cells-1 (TREM-1) and its putative ligand the neutrophil peptidoglycan recognition protein 1 (PGLYRP1) in saliva. Methods Forty-seven adolescents, aged 15 to 17 years, were tested with aMMP-8 PoC test, which was followed by a full-mouth clinical examination of the assessment of periodontal, mucosal, and oral health. TREM-1 and PGLYRP1 levels were analyzed by ELISA. The immunofluorometric assay (IFMA) specific for aMMP-8 was used as the reference method. Results Fourteen saliva samples out of a total of 47 showed positivity for aMMP-8 PoC test. Both the TREM-1 and the aMMP-8 (IFMA) levels were significantly elevated among the aMMP-8 PoC test positives compared with the PoC test negatives (P <0.05). Moreover, aMMP-8 levels assessed by IFMA showed a strong positive correlation with TREM-1 levels in saliva (r = 0.777, P <0.001). The number of sites with a probing depth of >= 4 mm was significantly lower among the adolescents that had a negative aMMP-8 PoC test result, and TREM-1 levels <75 pg/mL (P <0.05). In contrast, adolescents with a positive aMMP-8 PoC test result (i.e., elevated aMMP-8 levels) together with elevated TREM-1 levels had a significantly higher number of periodontal pockets with >= 4 mm (P <0.001). Conclusion The present study validated usability of aMMP-8 PoC test for predicting "proinflammatory" salivary profile and periodontal health status in adolescents.
  • Turunen, A.; Kuuliala, K.; Kuuliala, A.; Tervahartiala, T.; Mustonen, H.; Puolakkainen, P.; Kylänpää, A. L.; Sorsa, T. (2021)
    Objectives: Severe acute pancreatitis (SAP) has high morbidity and mortality but there are no widely accepted predictive biomarkers in clinical use. Matrix metalloproteinases (MMPs) are active in tissue destruction and inflammatory responses. We studied whether serum levels of activated MMP-8 (aMMP8), MMP-9 and their regulators tissue inhibitor of matrix metalloproteinases (TIMP)-1, myeloperoxidase (MPO) and human neutrophil elastase (HNE) could predict the development of SAP. Methods: The study comprised 214 AP patients (revised Atlanta classification: 142 mild, MAP; 54 moderately severe, MSAP; 18 SAP) referred to Helsinki University Hospital. A venous blood sample was taken within 72 h from the onset of symptoms. Serum levels of aMMP-8 were determined using immunofluorometric assay, and those of MMP-9, TIMP-1, MPO and HNE using enzyme-linked immunosorbent assay. AP groups were compared using Jonckheere-Terpstra test and predictive value for SAP was analyzed using receiver operating characteristics (ROC) analysis. Results: Serum aMMP-8 levels were higher in SAP (median 657 ng/ml, interquartile range 542-738 ng/ ml) compared to MSAP (358 ng/ml, 175-564 ng/ml; p < 0.001) and MAP (231 ng/ml, 128-507 ng/ml; p < 0.001). Similar trend was seen with TIMP-1 and MPO. In ROC analysis aMMP-8, MPO and TIMP-1 emerged as potential markers for the development of SAP (areas under ROC curves 0.83, 0.71 and 0.69, respectively). Conclusions: Serum aMMP-8 measured early in the course of AP (within 72 h of symptom onset) predicted the development of SAP. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • Räisänen, Ismo T.; Sorsa, Timo; van der Schoor, Gerrit-Jan; Tervahartiala, Taina; van der Schoor, Peter; Gieselmann, Dirk-Rolf; Heikkinen, Anna Maria (2019)
    This cross-sectional study compares the effectiveness of an active MMP-8 (aMMP-8) point-of-care (PoC)/chairside mouthrinse test to the conventional bleeding on probing (BOP) (cutoff 20%) test in detecting subclinical periodontitis/pre-periodontitis in Finnish adolescents. The study was carried out at the Kotka Health Center, Finland. A total of 47 adolescents (30 boys/17 girls) aged 15-17 were first tested with the aMMP-8 PoC test, followed by a full-mouth evaluation of clinical parameters of oral health including periodontal, oral mucosal, and caries assessment. A periodontist performed these clinical examinations. The aMMP-8 PoC test result had much stronger association with subclinical periodontitis than the BOP 20% test (2.8-5.3 times stronger in terms of odds ratio). The aMMP-8 PoC test had >= 2 times higher sensitivity than the BOP 20% test with, generally, the same specificity. Further, the aMMP-8 PoC test had generally better accuracy and lower false negative percentages. The aMMP-8 PoC test seemed to be more effective than the conventional BOP test in detecting subclinical periodontitis/pre-periodontitis in adolescents reducing the risk of their undertreatment. However, the sample size may be a limiting factor, and more studies are needed to confirm our results for both adolescents and adults.
  • Rautava, Jaana; Gürsoy, Ulvi K.; Kullström, Adrian; Kononen, Eija; Sorsa, Timo; Tervahartiala, Taina; Gürsoy, Mervi (2020)
    The diagnostic accuracy of point-of-care (PoC) applications may be compromised in individuals with additional inflammatory conditions. This cross-sectional study examined the performance of a commercial oral rinse active matrix metalloproteinase-8 (aMMP-8) PoC immunotest in individuals with (n = 47) and without Crohn's disease (CD) (n = 41). Oral rinse collected from the participants was analyzed by the PoC immunotest. Molecular forms and fragments of salivary MMP-8 were detected by western immunoblotting. The sensitivity of the immunotest for periodontitis was 60.0% in the CD group and 90.0% in the control group. The respective specificity was 75.0% and 80.0%. In both groups, clinical diagnosis of periodontitis exhibited a significant association with the immunotest results, however, the odds ratio (OR) was more than ten-fold in controls (OR 54.3, 95% CI: 3.1-953, p = 0.006) in comparison to CD patients (OR 5.2, 95% CI: 1.3-21.6, p = 0.022). According to Western immunoblot results, the immunotest MMP-8 positivity was not related to elevated levels of molecular forms and fragments of MMP-8 in the CD group, as in the control group. The diagnostic accuracy of the aMMP-8 PoC oral rinse immunotest is reduced in CD patients, which may be related to lower levels or undetectable complexes.
  • Golub, Lorne M.; Räisänen, Ismo T.; Sorsa, Timo; Preshaw, Philip M. (2020)
    Dental implants are widely utilized for the replacement of missing teeth and are increasingly being placed in patients with systemic diseases, as well as in those who are medically healthy. Furthermore, it is recognized that peri-implant mucositis and peri-implantitis are highly prevalent, affecting large numbers of patients with implants, and it is pertinent to consider whether there may be any systemic impact of these conditions, given that there are known links between periodontitis and a number of chronic inflammatory diseases. In this article, we propose that the potential systemic complications of peri-implant diseases should be investigated in future clinical research, together with studies to identify whether systemically-administered host modulation therapies (HMTs) may be of benefit in the treatment of peri-implant diseases. These "HMTs" may prove a useful adjunct to routinely employed debridement and disinfection protocols, as well as potentially being of benefit in reducing risks of systemic complications. We also consider the use of chair-side diagnostic tests for active matrix metalloproteinase-8 (aMMP-8) in the detection of peri-implant disease given the ability of such tests to detect active tissue breakdown associated with peri-implantitis and periodontitis before conventional clinical and radiographic measurements indicate pathologic changes. These novel diagnostic and therapeutic strategies are relevant to consider as they may improve the management of peri-implant disease (beyond local debridement procedures), especially in those patients in whom systemic inflammation might be of concern.
  • Mokkala, Kati; Juhila, Juuso; Houttu, Noora; Sorsa, Timo; Laitinen, Kirsi (2020)
    Lower level of insulin-like growth factor-binding protein (IGFBP-1) has been observed in insulin resistance, while higher level of matrix metalloproteinase-8 (MMP-8) has been linked to obesity. The aim here was to study in overweight and obese women, typically manifesting with insulin resistance, whether IGFBP-1 and MMP-8 are related to and reflect systemic low-grade inflammation, metabolism and diet. Fasting serum from overweight and obese pregnant women (n = 100) in early pregnancy were analysed for IGFBP-1, phosphorylated IGFBP-1 (phIGFBP-1) and MMP-8. High-sensitivity CRP and GlycA were used as markers for low grade inflammation. GlycA and lipids were quantified using NMR. IGFBP-1 associated negatively with GlycA, evidenced by higher concentrations in the lowest quartile (median 1.53 (IQR 1.45-1.72)) compared to the highest (1.46 (1.39-1.55)) (P = 0.03). Several lipid metabolites, particularly HDL-cholesterol, correlated inversely with phIGFBP-1 (FDR
  • Carpen, Timo; Sorsa, Timo; Jouhi, Lauri; Tervahartiala, Taina; Haglund, Caj; Syrjänen, Stina; Tarkkanen, Jussi; Mohamed, Hesham; Mäkitie, Antti; Hagström, Jaana; Mattila, Petri S. (2019)
    Background An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC. Materials and methods A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS). Results High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels. Conclusion Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.
  • Äyräväinen, Leena; Heikkinen, Anna Maria; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Laasonen, Leena; Moilanen, Eeva; Hämäläinen, Mari; Tervahartiala, Taina; Meurman, Jukka H.; Leirisalo-Repo, Marjatta; Sorsa, Timo (2018)
    Objective: To study prospectively the association of salivary and serum matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1 and interleukin (IL)-6 with periodontal and systemic inflammation in rheumatoid arthritis (RA). We hypothesized that biomarker concentrations reflect inflammation. Methods: Fifty three early untreated RA (ERA) and 28 chronic RA (CRA) patients, underwent rheumatological and dental examinations at baseline and one year later after starting first conventional or biological disease modifying antirheumatic drug. We included 43 control subjects. Saliva and serum samples were analyzed for MMP-8, TIMP-1 and IL-6. Periodontal health was assessed by bleeding on probing (BOP), pocket depth (PD) and periodontal inflammatory burden index (PIBI); RA disease activity was assessed by disease activity score DAS28. Joint destruction was analyzed by the modified Sharp-van der Heijde (SHS) method. Results: Serum MMP-8 (p <.001; p <.001) and IL-6 (p <.001; p =.002) were significantly higher in CRA vs. other study groups during the study. Salivary MMP-8 (p =.010) and IL-6 (p =.010) were significantly higher in ERA vs. other study groups at baseline. Salivary MMP-8 was associated with periodontal parameters. Conclusion: Elevated serum concentrations of MMP-8 and IL-6 in CRA patients reflected chronic RA, while elevated salivary concentrations of MMP-8 levels in ERA patients reflected increased periodontal inflammation.
  • Sinervä, Anu-Maria (University of Helsinki, 1997)
  • Niemi, Katriina Viola Elisabeth (Helsingin yliopisto, 2020)
    Matriksin metalloproteinaasi 8 on kollageenia hajottava ihmisen elimistön erittämä entsyymi. Se osallistuu normaaliin kudosten muokkaamiseen ja tulehduksellisiin sairauksiin, kuten syöpään, parodontiittiin ja sydän- ja verisuonitauteihin. Tässä tutkimuksessa aineistona ovat Pubmedistä haetut artikkelit ja FINRISK-tutkimuksessa vuonna 1997 kerätty aineisto 8349 henkilöltä. MMP-8-pitoisuus määritettiin tutkimushenkilöiden seerumista IFMA-menetelmällä. FINRISK-tutkimusaineistoa analysoitiin IMB SPSS Statistics-ohjelman avulla. Tulokseksi saatiin, että seerumin matriksin metalloproteinaasi 8:n pitoisuus on terveillä korkeampi kuin sairailla, kun tarkastellaan koko väestöä. Ikäryhmittäin tarkasteltuna ikäryhmien sisällä pitoisuus on kuitenkin sairailla korkeampi kuin terveillä. Matriksin metalloproteinaasi 8:n pitoisuus laskee iän myötä. Erot pitoisuudessa terveiden ja sairaiden välillä pienentyvät iän myötä. Viitearvot määritettiin tässä tutkimuksessa, ja ne ovat 5,33-241,2 ng/ml kaikille, naisille 5,61-250,1 ng/ml ja miehille 4,96-217,9 ng/ml. Terveillä ja sairailla tupakoitsijoilla pitoisuudet ovat käytännössä samat. Tupakoinnin lopettaneilla erot pitoisuudessa ovat terveiden ja sairaiden välillä suhteellisen suuret. Henkilöillä, joilla on metabolinen oireyhtymä, on matala matriksin metalloproteinaasi 8:n pitoisuus. Pitoisuus on tilastollisesti merkitsevästi matalampi myöhemmin puhkeavan diabeteksen suhteen. Tässä tutkimuksessa MMP-8:n pitoisuudet olivat sydän- ja verisuonisairauksia sairastavilla tutkittavilla henkilöillä matalat. Matriksin metalloproteinaasi 8:n pitoisuus korreloi positiivisesti CRP:n ja erityisen voimakkaasti fibrinogeenin kanssa. Vaikuttaa siltä, että kroonisesti sairailla pitoisuudet ovat matalat, akuutissa tilanteessa pitoisuudet nousevat ja ajan kuluessa laskevat takaisin mataliksi. Tämä koskee erityisesti sydän- ja verisuonitauteja. Hypoteesi tarvitsisi lisää tutkimusta, jotta pystyisimme MMP-8:n avulla seuraamaan ja ennustamaan taudinkulkua paremmin. (212 sanaa)
  • Kelppe, Jetta; Thoren, Hanna; Haglund, Caj; Sorsa, Timo; Hagström, Jaana (2021)
    Objectives Ameloblastoma is a benign, locally aggressive odontogenic tumor with high recurrence rates. Matrix metalloproteinases (MMPs) mediate extracellular integrity in normal and pathological conditions, and exert multiple functions coordinating inflammation and tumor progression. E-cadherin and beta-catenin are adherence junction molecules in cell-to-cell connections. We investigated the involvement of MMP-7, -8, -9, E-cadherin, and beta-catenin in ameloblastoma and the surrounding extracellular matrix. Material and methods Our material consisted of 30-34 tissue samples from ameloblastoma patients of Helsinki University Hospital. We used immunohistochemistry to detect the expression of the biomarkers. Two oral pathologists independently scored the immunoexpression intensities and statistical calculations were made based on the results. Results E-cadherin expression was weaker in the maxillary than in mandibular ameloblastomas. Beta-catenin was expressed in the ameloblastoma cell membranes. We detected MMP-8 and -9 expression in polymorphonuclear neutrophils in the extracellular area and these MMPs correlated positively with each other. Osteoclasts lining bone margins and multinuclear giant cells expressed MMP-9. Neither MMP-8 nor MMP-9 immunoexpression could be detected in ameloblastoma cells. MMP-7 expression was seen in some apoptotic cells. Conclusion The fact that E-cadherin immunoexpression was weaker in maxillary compared to mandibular ameloblastomas might associate to earlier recurrences. It promotes the idea of mandibular and maxillary ameloblastoma exerting differences in their biologies. We detected MMP-8 and -9 in polymorphonuclear neutrophils which relates to these MMPs participating in extracellular remodeling through a mild inflammatory process. Bone degradation around ameloblastoma may be due to MMP-9 in osteoclasts but this phenomenon might be an independent process and needs further investigations.
  • Kiili, Markus Tapio (Helsingfors universitet, 2005)
    Parodontiitti eli hampaan tukikudoksen tulehdus on ihmisten ja koirien yleisin suusairaus, jolle on tunnusomaista hammasta ympäröivä kudostuho. Kudostuhon aiheuttajana ovat plakkibakteereiden tuottamat ja elimistön omiin puolustusreaktioihin liittyvät tulehduksen välittäjäaineet. Elimistön omista kudostuhoa aiheuttavista aineista tärkeimpinä pidetään kolleganolyyttejä eli kollageenin hajottajia ja niistä nimenomaan tiettyjä matriksin metalloproteinaaseja (MMP). Parodontiitille on tyypillistä kroonisuus ja taudin eteneminen pyräyksittäin, joten sen tarkkaa ennustetta on usein vaikea arvioida. Uusimpien MMP- tutkimusten tarkoituksena on löytää tarkempia menetelmiä parodontiittipotilaiden taudin aktiviteetin arviointiin ja siten hoidon suuntaamiseen oikein valituille potilaille. Myös spesifisiä matriksin metalloproteinaasien inhibiittoreita on tutkittu mahdollisina lääkkeinä parodontiitin hoitoon. Nämä syventävät opinnot pohjautuvat artikkeliini matriksin metalloproteinaasien mittauksesta kroonista parodontiittia sairastavien ihmisten iennesteestä ja ikenen kudosnäytteistä. Tutkimuksen tarkoituksena oli selvittää MMP-8:n ja MMP-13:n eri molekyylimuotojen esiintymistä kroonisessa parodontiitissa, sekä tutkia mitkä eri solut niitä erittävät. Kahdeltatoista hoitamatonta parodontiittia sairastavalta keski-ikäiseltä ihmiseltä kerättiin 30 ientaskunäytettä määrämittaisilla imupaperisuikaleilla. Näytteet liuotettiin puskuriliuokseen, joka analysoitiin Western immunoblotting menetelmällä käyttäen kanissa tehtyjä polyklonaalisia MMP-8 ja MMP-13 vasta-aineita. Ienkudosnäytteet kerättiin kuudelta kroonista parodontiittia sairastavalta ihmiseltä. MMP-8 ja MMP-13 paikallistettiin käyttäen samoja vasta-aineita ja avidiini-biotiini-peroksidaasi detektiomenetelmää. Ennen hoitoa otettujen ientaskunestenäytteiden todetusta MMP-8:sta suurin osa oli molekyylipainoltaan 80kD, 75kD ja 60kD vastaten prepro-, pro- ja aktiivista muotoa neutrofiilityypin entsyymistä. 43kD ja 38kD painoiset aktiiviset fibroblastityyppiset entsyymit olivat toiseksi suurin ryhmä. Lisäksi todettiin jonkin verran >100kD ja <30kD painoisia tuotteita vastaten todennäköisesti MMP-8:n kompleksimuotoa ja pilkkoutumistuotteita. MMP-13 pääasiallinen molekyylimuoto oli 60kD proentsyymi, mutta myös 40kD aktiivista muotoa esiintyi. Joissakin näytteissä oli hieman myös >100kD kompleksimuotoja. Sekä MMP-8, että MMP-13 pitoisuudet ennen ja jälkeen hoidon otetuissa näytteissä korreloivat ikenen verenvuoto indeksin kanssa (p<0,05). Immunohistokemiallisessa analyysissä MMP-8 todettiin esiintyvän neutrofiileissä, ientaskuepiteelissä ja ikenen tulehtuneen sidekudoksen plasmasoluissa. MMP-13 immunoreaktiivisuutta havaittiin ientaskuepiteelissä ja makrofagityypin soluissa.
  • Lundmark, Anna; Johannsen, Gunnar; Eriksson, Kaja; Kats, Anna; Jansson, Leif; Tervahartiala, Taina; Rathnayake, Nilminie; Akerman, Sigvard; Klinge, Bjorn; Sorsa, Timo; Yucel-Lindberg, Tulay (2017)
    Aim: Periodontitis is a chronic inflammatory disease, characterized by irreversible destruction of tooth-supporting tissue including alveolar bone. We recently reported mucin 4 ( MUC4) and matrix metalloproteinase 7 (MMP7) as highly associated with periodontitis in gingival tissue biopsies. The aim of this study was to further investigate the levels of MUC4 and MMP7 in saliva and gingival crevicular fluid (GCF) samples of patients with periodontitis. Materials and Methods: Saliva and GCF samples were collected from periodontitis patients and healthy controls. The levels of MUC4, MMP7, and total protein concentrations were analysed using ELISA or Bradford assay. Results: MUC4 levels were significantly lower in saliva and GCF from periodontitis patients relative to healthy controls. MMP7 levels were significantly higher in saliva and GCF from periodontitis patients. Multivariate analysis revealed that MUC4 was significantly associated with periodontitis after adjusting for age and smoking habits and, moreover, that the combination of MUC4 and MMP7 accurately discriminated periodontitis from healthy controls. Conclusions: MUC4 and MMP7 may be utilized as possible novel biomarkers for periodontitis.
  • Räisänen, Ismo T.; Heikkinen, Anna Maria; Nwhator, Solomon O.; Umeizudike, Kehinde A.; Tervahartiala, Taina; Sorsa, Timo (2019)
    This study investigated the diagnostic utility of mouthrinse and saliva in aMMP-8 measurements to analyze patients' risk for active periodontal tissue destruction and progression of periodontal disease among 47 adolescents. Results show that measurements from mouthrinse produce better discrimination and should be used instead of saliva measurements. (C) 2019 Elsevier Inc. All rights reserved.
  • Räisänen, Ismo T.; Umeizudike, Kehinde A.; Pärnänen, Pirjo; Heikkilä, Pia; Tervahartiala, Taina; Nwhator, Solomon O.; Grigoriadis, Andreas; Sakellari, Dimitra; Sorsa, Timo (2020)
    Periodontal disease is a chronic multifactorial infectious and inflammatory disease associated with several chronic systemic diseases, such as diabetes, cardiovascular diseases (CVD), chronic obstructive pulmonary disease, hypertension, Alzheimer's disease and so on. These same systemic diseases have been associated with severe COVID-19 infections. Several recent studies have suggested hypotheses for the potential association between periodontal disease and severe COVID-19. Periodontal disease is also one of the most prevalent diseases globally. All this supports the importance of good oral health, also in the COVID-19 era. Thus, new strategies and approaches to identify patients at risk of periodontal disease could be beneficial to enhance secondary prevention, especially if targeted to COVID-19 risk groups. Diagnostic biomarkers for periodontal disease have been researched extensively. Potential biomarkers in oral fluid with currently available rapid non-invasive point-of-care technology, such as aMMP-8, could help to extend screening and identification of patients at risk for periodontal disease also to situations and places where professional dental expertise and equipment are limited or unavailable. i.e., nursing and care homes, and rural and distant places. The oral fluid point-of-care technologies could also be useful in the hands of medical professionals (diabetes, CVD, etc.) to identify patients at risk for undiagnosed periodontal disease and to refer them to a dentist for examination and evaluation. Finally, if there is a causality between periodontal disease and severe COVID-19 infections, these point-of-care oral fluid biomarker technologies could possibly also help in the assessment of the risk of deterioration and complications.
  • Petain, Sami; Kasnak, Gokhan; Firatli, Erhan; Tervahartiala, Taina; Gürsoy, Ulvi K.; Sorsa, Timo (2021)
    Background and Aims: Chymotrypsin-like-proteinase of Treponema denticola (Td-CTLP) can stimulate the protein expression and activation of matrix metalloproteinase (MMP)-8 (or collagenase-2), a potent tissue destructive enzyme from gingival cells in vitro. The aims of this study were 1) to demonstrate the proMMP-8 (or latent MMP-8) activation by Td-CTLP in vitro and 2) to detect Td-CTLP and MMP-8 protein levels in the tissue samples of peri-implantitis and periodontitis patients. Materials and Methods: proMMP-8 activation by Td-CTLP was analyzed by immunoblots. Tissue specimens were collected from 38 systemically healthy and non-smoking patients; 14 of whom had moderate to severe periodontitis, 10 of whom were suffering from peri-implantitis, and finally 14 of whom showed no sign of periodontal inflammation nor radiological bone decay (control group). The immune-expression levels of MMP-8 and Td-CTLP in the epithelium and the connective tissue were analyzed immunohistochemically. A pixel color-intensity analyze was performed with ImageJ software (version 1.46c; Rasband WS, National Institutes of Health, Bethesda, MD, USA) to obtain a comparable numeral score for each patient's epithelium and connective tissue MMP-8 and Td-CTLP enzyme level. Results: Td-CTLP activated proMMP-8 in vitro by converting the 70 75 kDa proMMP-8 to 65 kDa active MMP-8. Also, lower molecular size 25 50 kDa parts of MMP-8 were formed. There was no statistically significant difference between the study groups in terms of their MMP-8 and Td-CTLP levels in the epithelium or in the connective tissue. Conclusion: Regarding the limits of this study, it can thus be said that the Td-CTLP enzyme can activate the host proMMP-8 enzyme. Tissue protein levels of MMP-8 and Td-CTLP do not seem to be changed in peri-implantitis and in periodontitis.
  • Räisänen, Ismo T.; Heikkinen, Anna Maria; Siren, Eva; Tervahartiala, Taina; Gieselmann, Dirk-Rolf; van der Schoor, Gerrit-Jan; van der Schoor, Peter; Sorsa, Timo (2018)
    Traditional periodontal disease diagnostics are based mainly on clinical examination and radiographs. They assess only past tissue destruction and provide no information on the current disease status or its future progression. The objective is to find out if an active matrix metalloproteinase-8 (aMMP-8) point-of-care (PoC) test could provide a cost-effective way to get around this limitation. This cross-sectional study used 47 adolescents and 70 adults, who were clinically examined and their aMMP-8 PoC tested. The aMMP-8 PoC test results and patients' treatment need, based on the community periodontal index of treatment needs (CPITN), were compared and analyzed using Fisher's exact test. In terms of CPITN, the aMMP-8 PoC test gave no false positives for both adolescents and adults. All healthy patients got a negative test result, while a positive test result indicated periodontal treatment need correctly. Finally, there was a significant association between a patient's aMMP-8 PoC test result and his/her treatment need (p = 0.001 for adolescents, p = 0.001 for adults). In conclusion, more accurate diagnostics of periodontal diseases' activity and progression using an aMMP-8 PoC test may help to reduce oral health care costs by reducing patient overtreatment, improving patient outcome, and reducing the need for complex periodontal therapy.
  • Rathnayake, Nilminie; Akerman, Sigvard; Klinge, Bjorn; Lundegren, Nina; Jansson, Henrik; Tryselius, Ylva; Sorsa, Timo; Gustafsson, Anders (2013)
  • Pakkanen, Pihla P.; Aaltonen, Leena-Maija; Sorsa, Timo A.; Tervahartiala, Taina I.; Hagstroem, Jaana K.; Ilmarinen, Taru T. (2019)
    Background Biomarkers that could predict malignant transformation of recurrent respiratory papillomatosis (RRP) would be useful in patient follow-up. We investigated whether serum matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of metalloproteinase 1 (TIMP-1) could predict malignant transformation of RRP and whether they associate with survival in laryngeal squamous cell carcinoma (LSCC) without preexisting RRP. Methods We analyzed serum MMP-8 (S-MMP-8) and serum TIMP-1 (s-TIMP-1) in 114 patients: 55 were treated for RRP and 59 for LSCC without preexisting RRP. Five patients with RRP developed LSCC during follow-up. Results Elevated S-MMP-8 level in RRP was associated with malignant transformation (P = .01). Compared to patients with RRP, S-MMP-8 in patients with LSCC was significantly higher (P <.001). Increased S-TIMP-1 level in LSCC was associated with poor overall survival (P = .02) and recurrence-free survival (P = .05). Conclusion In RRP, high S-MMP-8 may predict malignant transformation. In LSCC, elevated S-TIMP-1 is connected to poor survival.
  • Palm, Frederick; Pussinen, Pirkko J.; Safer, Anton; Tervahartiala, Taina; Sorsa, Timo; Urbanek, Christian; Becher, Heiko; Grau, Armin J. (2018)
    Background and aims: Matrix metalloproteinase (MMP)-8 and myeloperoxidase (MPO) may contribute to cerebral damage in acute ischemic stroke. We tested the hypothesis that levels of MPO, MMP-8 and the ratio between MMP-8 and its regulator, tissue inhibitor of metalloproteinase (TIMP-1), are increased in acute ischemic stroke and its etiologic subgroups and they correlate with stroke severity. Methods: In a cross-sectional case-control study, serum concentrations of MMP-8, MPO and TIMP-1 were assessed within 24 h after admission in 470 first-ever ischemic stroke patients and 809 age-and sex-matched controls, randomly selected from the population. Odds ratios (OR) per decade of log transformed dependent variables were calculated and adjusted for age, sex and vascular risk factors. Results: Levels of MMP-8 (OR 4.9; 95% CI 3.4-7.2), MMP-8/TIMP-1 ratio (3.0; 2.2-4.1) and MPO (6.6; 4.0-11.0) were independently associated with ischemic stroke. MMP-8 levels differed between etiologic stroke subgroups (p = 0.019, ANOVA), with higher levels in cardioembolic stroke and stroke due to large vessel disease, and lower levels in microangiopathic stroke. MMP-8, MMP-8/TIMP-1 ratio and MPO (p <0.001) concentrations showed positive associations with stroke severity independent of stroke etiology. Conclusions: Concentrations of serum neutrophil markers are increased after ischemic stroke and associate with stroke severity and etiology. The value of these biomarkers in diagnostics and prognostics is worth being evaluated. (C) 2018 Elsevier B.V. All rights reserved.