| 1. |
- Hedenbjörk-Lager, Anders, et al.
(author)
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Caries correlates strongly with salivary levels of Matrix Metalloproteinase-8
- 2015
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In: Caries Research. - : S. Karger. - 0008-6568 .- 1421-976X. ; 49:1, s. 1-8
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Journal article (peer-reviewed)abstract
- The caries process in dentin involves the degradation of both mineral and organic matrix. The demineralization has been demonstrated to be caused by bacterial acids. How-ever, the collagen degradation is considered to be initiated by endogenous proteolytic enzymes, mainly collagenolytic matrix metalloproteinases (MMPs). This paper aims to relate salivary MMP-8 (or salivary collagenase-2) and tissue inhibi-tor of MMP (TIMP-1) levels to manifest caries in a large num-ber of subjects. A random sample of 451 adults (aged 18-87 years) living in the south of Sweden was included in this study. Standard clinical examinations were performed, and stimulated saliva was collected and analyzed for concentra-tions of MMP-8, TIMP-1 and total protein, using an immuno-fluorometric assay, an enzyme-linked immunosorbent assay and the Bradford assay, respectively. Salivary numbers of mutans streptococci and lactobacilli were determined using a chair-side kit. Subjects with manifest caries lesions present-ed with elevated levels of MMP-8 (p < 0.001) as well as total protein, MMP-8/TIMP-1 ratio, bleeding on probing and plaque index (p = 0.05) compared with subjects without manifest caries. Multiple linear regression analysis with car-ies as the dependent variable revealed MMP-8 as the only significant explanatory variable (p < 0.001). TIMP-1 was not significant in any case. Using MMP-8 as the dependent vari-able revealed total protein concentration, caries lesions (p ≤ 0.001) and salivary secretion rate (p = 0.05) as explanatory variables. In conclusion, our data reveal that subjects with manifest caries lesions have elevated levels of salivary MMP-8 relative to subjects with no caries lesions.
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| 2. |
- Bjørndal, Lars, et al.
(author)
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Randomized Clinical Trials on Deep Carious Lesions : 5-Year Follow-up
- 2017
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In: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 96:7, s. 747-753
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Journal article (peer-reviewed)abstract
- Deep caries presents a dilemma in terms of which treatment that will render an optimal prognosis by maintaining pulp vitality with absence of apical pathology. Previously, 2 randomized clinical trials were performed testing the short-term effects of stepwise carious tissue removal versus nonselective carious removal to hard dentin with or without pulp exposure. The aim of this article was to report the 5-y outcome on these previously treated patients having radiographically well-defined carious lesions extending into the pulpal quarter of the dentin but with a well-defined radiodense zone between the carious lesion and the pulp. In this long-term study, 239 of 314 (76.2%) patients were analyzed. The stepwise removal group had a significantly higher proportion of success (60.2%) at 5-y follow-up compared with the nonselective carious removal to hard dentin group (46.3%) ( P = 0.031) when pulp exposures per se were included as failures. Pulp exposure rate was significantly lower in the stepwise carious removal group (21.2% vs. 35.5%; P = 0.014). Irrespective of pulp exposure status, the difference (13.3%) was still significant when sustained pulp vitality without apical radiolucency and unbearable pain was considered (95% confidence interval, 3.1-26.3, P = 0.045). After pulp exposure, only 9% ( n = 4) of the analyzed patients were assessed as successful, indicating that the prognosis is highly dubious following conventional pulp-capping procedures (direct pulp capping or partial pulpotomy) in deep carious lesions in adults. In conclusion, the stepwise carious removal group had a significantly higher proportion of pulps with sustained vitality without apical radiolucency versus nonselective carious removal of deep carious lesions in adult teeth at 5-y follow-up (ClinicalTrials.gov NCT00187837 and NCT00187850).
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| 3. |
- Flink, Håkan, et al.
(author)
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Identification of caries-active individuals in longitudinal data a methodological study using a national registry
- 2024
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In: Acta Odontologica Scandinavica. - : Medical Journals Sweden. - 0001-6357 .- 1502-3850. ; 83, s. 70-75
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Journal article (peer-reviewed)abstract
- ObjectiveThe aim was to identify caries active individuals among adults by using a trajectory model of longitudinal data from the Swedish national registry (SKaPa) and comparing them with published data from the Dunedin cohort.Materials and methodsData from two different age groups (30- and 40-year-olds) followed for 10 years were retrieved from SKaPa and were compared with published longitudinal birth-cohort data from the Dunedin study. Using the trajectory model, the subjects were divided into three different trajectories according to their caries development over time (i.e. high, 15%; moderate, 45%; low, 40%).ResultsCaries experience, as measured by mean decayed, missing, and filled surfaces (DMFS) index, revealed significant differences among the three trajectories in both age groups. The patterns were similar to those observed in the Dunedin cohort. The mean increase in DMFS during the 10-year follow-up period from SKaPa was significantly higher for the high trajectories in both age groups compared with the moderate and low trajectories.ConclusionsThe method using three trajectories for presentation of caries experience over time, may be a useful tool to identify subjects with different disease activities. Identification of subjects in the high caries experience trajectory may increase the possibility to explore and evaluate more effective caries prevention for this group in the future.
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| 4. |
- Flink, Håkan, et al.
(author)
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Identification of Swedish caries active individuals aged 30-90 years using a life course perspective and SKaPa longitudinal national registry data over a 10-year period
- 2024
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In: Acta Odontologica Scandinavica. - : Medical Journals Sweden. - 0001-6357 .- 1502-3850. ; 83, s. 412-418
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Journal article (peer-reviewed)abstract
- Objective: To describe the occurrence of caries disease from a life course perspective using longitudinal data from the Swedish Quality Registry for Caries and Periodontal Disease (SKaPa). Material and Methods: Data from seven age cohorts (ages 30-90 years), each followed over 10 years, were retrieved from the SKaPa. Using a three-trajectory model, individuals were divided into three trajectories according to their caries development over time: high (15%), moderate (45%), or low (40%). Caries experience was expressed as the mean decayed, missing, and filled surfaces (DMFS) index. Results: Significant differences were found for all three trajectories and in all age groups over the 10 years. The mean DMFS index increase was significantly larger for the high trajectory group than for the moderate and low trajectory groups across all age cohorts. An increase in caries experience was observed for the older cohorts across all trajectories. Conclusions: A three-trajectory model appears useful for identifying and quantifying caries experiences in longitudinal studies. Increased caries disease occurs over time, especially in the highest trajectory group and among older cohorts. These findings emphasise the need for greater attention and more efficient caries prevention methods.
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| 5. |
- Hedenbjörk Lager, Anders, et al.
(author)
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Aciduric Bacterial Communities at Three Levels in Dentin Caries
- 2013
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In: Oral Health & Preventive Dentistry. - : Quintessence. - 1602-1622 .- 1757-9996. ; 11:4, s. 359-367
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Journal article (peer-reviewed)abstract
- Purpose: Dentin caries constitute a complex ecosystem with a diverse microbiota adapted to fluctuations in nutrient concentration and acidity. However, knowledge about the acid tolerant microbiota at different levels in the lesion is rather poor. Hence, the purpose of this study was to investigate the acid tolerant microflora at different levels in established dentin caries lesions using solid pH-selective media. Materials and Methods: Primary dentin caries lesions were sampled with a bur at three levels (superficial, centre and the clinically caries-free floor of the lesion) in 10 patients. Samples were incubated on pH-neutral and pH-selective (pH 4.0, 4.5, 5.0, 5.5) agars. Numbers of colony-forming units (cfu) were determined and colonies were subsequently characterised morphologically and isolated. Results: The total number of bacteria in the carious lesions, recovered using blood agar (BA), ranged from 5.88 x 103 to 5.85 x 105 (median 2.64 x 105; range 5.80 x 105) and numbers of recovered bacteria decreased with decreasing agar pH. Fewer bacteria were found in the clinically caries-free dentin (P = 0.042), but the mean number of cfu (BA) was still 5.88 x 103 in those samples. Conclusion: Each of the 10 investigated dentin caries lesions harboured a unique microbial flora, indicating that various combinations of aciduric bacteria can colonise, survive in and probably propagate dentin caries. Solid pH-selective agars can be used successfully to select acid-tolerant microorganisms in dentin caries lesions. This could be used to describe this subset of the total microbiome from a phenotypic point of view, an objective that cannot be accomplished using molecular methods.
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| 6. |
- Hedenbjörk-Lager, Anders, et al.
(author)
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Collagen degradation and preservation of MMP-8 activity in human dentine matrix after demineralization
- 2016
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In: Archives of Oral Biology. - : Elsevier. - 0003-9969 .- 1879-1506. ; 68, s. 66-72
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Dental caries is a process driven by acids produced by oral microorganisms followed by degradation of the dentine collagen matrix by proteolytic enzymes. Matrix metalloproteinases (MMPs) have been suggested to contribute to caries by degrading collagen. The aim of this study was to develop a method for generating demineralized dentine matrix substrate (DDM) maintaining MMP-8 bioactivity and no interference with later assays. Such a substrate would allow study of the effects of various treatments on MMP-8 activity and collagen degradation in demineralized dentine. DESIGN: Human dentine was powderized in a tissue grinder and frozen (-80°C). The powder was demineralized in dialysis tubes, using EDTA or acetic acid. The demineralized dentine matrix (DDM) was harvested and analyzed for collagen content using SDS-PAGE. The DDM was subsequently suspended in PBS or TESCA buffer. Protein, MMP-8 (ELISA) and collagen (HYP) was analyzed directly or after 1 wk. RESULTS: EDTA or acid demineralization of dentine using dialysis yielded a substrate rich in collagen coupled with preserved MMP-8 activity. Collagen degraded in room temperature, assessed by higher HYP amounts in the soluble fraction of DDM after one wk, indicating that the methods used preserved active DDM-components after the demineralization process. CONCLUSIONS: The presented demineralization methods both provided insoluble DDM substrates suitable for further intervention studies. However, it was found that the substrates differed depending on the demineralization method and buffers used. This needs further study to find an optimal technique for generating DDM with retained proteins as well as enzymatic bioactivity.
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| 7. |
- Hedenbjörk Lager, Anders
(author)
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Dentine caries : acid tolerant microorganisms and aspects on collagen degradation
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Karies är en stor folksjukdom, trots att den både kan förebyggas och behandlas effektivt. Om man inte ingriper preventivt och låter det naturliga förloppet råda, kommer kariesangreppet till slut att bryta igenom emaljen och involvera även den underliggande dentinvävnaden. Kariessjukdomen orsakas av orala mikroorganismer, som en konsekvens av dessas nedbrytning av kostrelaterade kolhydrater. Som en biprodukt bildas då syror som löser upp (demineraliserar tandvävnaden), så att synliga hål till slut bildas. Syran kan lösa upp mineralfasen i tanden, men dentin består även till stor del av kollagen, vilket inte kan lösas upp av enbart syror. Man hänförde länge detta till proteinnedbrytande bakterier, men det har visat sig att munhålebakterierna inte har förmågan att lösa upp kollagen, och man tror nu att denna nedbrytning sker med hjälp av kroppsegna enzymer, bland annat matrix metalloproteinaser (MMP). De biologiska mekanismerna bakom kollagennedbrytning vid dentinkaries är emellertid dåligt undersökta, och delar av denna rapport (Studie III och IV) inriktar sig därför på detta område. Syran som bakterierna bildar skapar också en sur närmiljö för dem själva, vilket gör det svårt för dem att överleva, särskilt i ett begränsat utrymme som ett kariesangrepp. Man har länge ansett att endast vissa specifika bakterier har förmågan att leva och trivas i sura miljöer, men nya studier har ifrågasatt detta. I denna rapport (Studie II) undersöks även förekomsten av syratåliga bakterier på olika nivåer i dentinkariesangrepp med hjälp av en ny metod. Målet vid avlägsnande av karies är att ta bort fullständigt förstörd tandvävnad, men att försöka spara så mycket som möjligt av den delvis skadade vävnaden, vilken kan återställas. Detta har också aktualiserats då nya operativa principer och material lanserats under den senaste tioårsperioden. Det är emellertid svårt att avgöra var gränsen går kliniskt, och ett sätt att mäta dentinets ”friskhet” kan vara att mäta antalet bakterier i vävnaden. I den första rapporten (Studie I) undersöks den kvarvarande bakterieförekomsten efter kariesborttagning med två olika operativa metoder. Avhandlingen söker svar på följande frågeställningar: Studie I. Finns det några skillnader vad gäller antal kvarvarande bakterier efter dentinkariesavlägsnande med mekanisk (vanligt borr) eller kemo-mekanisk (Carisolv) metod? Studie II. Hur ser sammansättningen av den syratåliga bakteriefloran ut på tre olika nivåer i olika dentinkariesangrepp? Studie III. Finns det något samband mellan förekomsten av etablerade kariesangrepp och nivåerna av enzymet MMP-8 och dess nedreglerande protein TIMP-1 i saliv? Studie IV. Kan man framställa demineraliserat dentinmatrix med bibehållen biologisk aktivitet inför framtida studier av mekanismerna bakom nedbrytning av kollagen vid dentinkaries? Vad händer spontant med detta demineraliserade dentinmatrix över tid? Huvudfynden i studierna är: 1. Båda metoderna för att avlägsna dentinkaries minskade bakterieantalet radikalt. Det finns dock alltid kvar små mängder av bakterier i kaviteten. 2. Alla de undersökta kaviteterna hade en unik sammansättning av syratåliga bakterier, både till typ och antal, vilket indikerar att ett flertal olika bakterier har förmågan att anpassa sig till sura miljöer och potentiellt bidra till kariesutvecklingen. Vidare, fungerade de pH-specifika odlingsmedierna väl för att få fram de syratåliga bakterierna, något som är svårt med konventionella metoder. 3. Försökspersoner med etablerade dentinkariesangrepp uppvisade mycket högre förekomst av MMP-8 i saliven jämfört med kariesfria försökspersoner. Det nedreglerande proteinet TIMP-1 uppvisade inga samband alls. 4. Dentinmatrix framställt med båda testmetoderna uppvisade förekomst av intakt kollagen, samt aktivt MMP-8. Vidare så uppvisades en spontan nedbrytning av kollagen över tid, vilket tolkades som mestadels ett resultat av det aktiva MMP-8 enzymet. De nyvunna grundkunskaperna bildar underlag för nya studier inom forskningsområdet, samt för nya behandlingsmetoder, framför allt sådana som skulle kunna moderera eller förhindra dentinkariesprogression.
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| 8. |
- Nordström, Marie, et al.
(author)
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Common resilience factors among healthy individuals exposed to chronic adversity : a systematic review
- 2023
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In: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 81:3, s. 176-185
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Research review (peer-reviewed)abstract
- Objective: To identify common resilience factors against non-communicable diseases (dental caries, diabetes type II, obesity and cardiovascular disease) among healthy individuals exposed to chronic adversity.Materials and methods: The databases MEDLINE (via PubMed), Scopus and CINAHL were searched. Observational studies in English assessing resilience factors among populations living in chronic adversity were included. Intervention studies, systematic reviews, non-original articles and qualitative studies were excluded. There were no restrictions regarding publication year or age. No meta-analysis could be done. Quality assessments were made with the Newcastle-Ottawa scale (NOS).Results: A final total of 41 studies were included in this systematic review. The investigated health resilience factors were divided into the following domains: environmental (community and family) and individual (behavioural and psychosocial). A narrative synthesis of the results was made according to the domains.Conclusions: Individual psychosocial, family and environmental factors play a role as health resilience factors in populations living in chronic adversity. However, the inconclusive results suggest that these factors do not act in isolation but interplay in a complex manner and that their interaction may vary during the life course, in different contexts, and over time.
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| 9. |
- Odlén, Karin, et al.
(author)
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Odontoblast-like MDPC-23 cells produce pro-inflammatory IL-6 in response to lipoteichoic acid and express the antimicrobial peptide CRAMP.
- 2020
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In: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 78:3, s. 210-216
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Journal article (peer-reviewed)abstract
- Odontoblasts are thought to be involved in innate immunity but their precise role in this process is not fully understood. Here, we assess effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA), produced by Gram-negative and Gram-positive bacteria, respectively, on matrix metalloproteinase-8 (MMP-8), interleukin-6 (IL-6) and cathelin-related antimicrobial peptide (CRAMP) expression in odontoblast-like MDPC-23 cells. Gene activity and protein production was determined by quantitative real-time RT-PCR and ELISA, respectively. Cellular expression of CRAMP was determined by immunocytochemistry. Stimulation with LTA (5 and 25 µg/ml) but not LPS (1 and 5 µg/ml) for 24 h enhanced IL-6 mRNA expression. The LTA-induced up-regulation of IL-6 mRNA levels was associated with increased IL-6 protein levels. Stimulation with either LPS or LTA for 24 h lacked effect on both MMP-8 transcript and protein expression. Immunocytochemistry disclosed that MDPC-23 cells expressed immunoreactivity for CRAMP. MDPC-23 cells showed mRNA expression for CRAMP, but stimulation with either LPS or LTA did not modulate CRAMP transcript expression. We show that MDPC-23 cells possess immune-like cell properties such as LTA-induced IL-6 production and expression of the antimicrobial peptide CRAMP, suggesting that odontoblasts may modulate innate immunity via these mechanisms.
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