| 1. |
- Esberg, Anders, et al.
(författare)
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LIGHT protein : a novel gingival crevicular fluid biomarker associated with increased probing depth after periodontal surgery
- 2024
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Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 51:7, s. 852-862
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate the protein profiles in gingival crevicular fluid (GCF) in relation to clinical outcomes after periodontal surgery and examine if any selected proteins affect the mRNA expression of pro-inflammatory cytokines in human gingival fibroblasts.Materials and Methods: This exploratory study included 21 consecutive patients with periodontitis. GCF was collected, and the protein pattern (n = 92) and clinical parameters were evaluated prior to surgery and 3, 6 and 12 months after surgery. Fibroblastic gene expression was analysed by real-time quantitative polymerase chain reaction.Results: Surgical treatment reduced periodontal pocket depth (PPD) and changed the GCF protein pattern. Twelve months after surgery, 17% of the pockets showed an increase in PPD. Levels of a number of proteins in the GCF decreased after surgical treatment but increased with early signs of tissue destruction, with LIGHT being one of the proteins that showed the strongest association. Furthermore, LIGHT up-regulated the mRNA expression of pro-inflammatory cytokines interleukin (IL)-6, IL-8 and MMP9 in human gingival fibroblasts.Conclusions: LIGHT can potentially detect subjects at high risk of periodontitis recurrence after surgical treatment. Moreover, LIGHT induces the expression of inflammatory cytokines and tissue-degrading enzymes in gingival fibroblasts.
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| 2. |
- Esberg, Anders, et al.
(författare)
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Peri-implant crevicular fluid proteome before and after adjunctive enamel matrix derivative treatment of peri-implantitis
- 2019
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Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 46:6, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study was to explore which peri‐implant crevicular fluid (PICF) protein pattern is associated with the active peri‐implantitis process.Materials and methods: Peri‐implant crevicular fluid from 25 peri‐implantitis sites were subjected to proteomic analysis using liquid chromatography–tandem mass spectrometry before and at 3, 6 and 12 months after treatment, to identify associations between PICF protein pattern and implant loss, bleeding on probing, pocket depth and enamel matrix derivative (EMD) treatment.Results: Clustering of subjects based on their 3–12 months PICF proteomic profiles by principal component analysis defined two major clusters. Cluster 2 differentiated from cluster 3 by 52 proteins (R2 = 90%, Q2 = 80%) and belonging to cluster 2 was associated with implant loss (p = 0.009) and bleeding on probing (p = 0.001). Cluster 3 was associated with implant survival and EMD treatment (p = 0.044).Conclusion: Here, we demonstrate that a specific PICF proteomic profile associates with active peri‐implantitis process and implant loss.
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| 3. |
- Esberg, Anders, et al.
(författare)
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PICF proteome before and after adjunctive EMD treatment of peri-implantitis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The aim of this study was to explore which peri-implant crevicular fluid (PICF) protein patter that are associated with the active peri-implantitis process.Materials and methods: PICF from 25 peri-implantitis sites were subjected to proteomic analysis using liquid chromatography-tandem mass spectrometry before and at 3, 6 and 12 months after treatment, to identify associations between protein expression and implant loss, radiographic bone level change, bleeding on probing, pocket depth, and enamel matrix derivative (EMD) treatment. Results: Clustering of subjects based on their 3 to 12 months PICF proteomic profiles by principal component analysis defined two major clusters. Cluster 2 was differentiated from cluster 3 by 52 proteins (R2=90%, Q2=80%) and belonging to cluster 2 had an odds ratio for implant loss of 7.9 (95% confidence interval 1.8 to 35.9). Cluster 3 was related to implant survival (p=0.007) after 5 years and associated with EMD treatment (p=0.044). Furthermore, cluster 2 was associated with radiographic bone loss (p<0.0001) and bleeding on probing (p=0.001). Conclusion: EMD treatment was associated with the PICF proteomic profile related to implant survival. EMD reduced number of proteins, dominated by proteins associated with implant loss. However, whether these effects are direct or indirect requires further exploration.
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| 4. |
- Esberg, Anders, et al.
(författare)
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Serum proteins associated with periodontitis relapse post-surgery: A pilot study
- 2021
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Ingår i: Journal of Periodontology. - : John Wiley & Sons. - 0022-3492 .- 1943-3670. ; 92:12, s. 1805-1814
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Tidskriftsartikel (refereegranskat)abstract
- Background: The knowledge of which genes and proteins that are connected to the susceptibility to gingivitis with subsequent local tissue degradation seen in periodontitis is insufficient. Changes of serum proteins associated with recurrence of bleeding on probing (BOP) and increased periodontal pocket depths (PPD) after surgical treatment of periodontitis could reveal molecules that could be early signals of tissue destruction and/or of importance for systemic effects in other tissues or organs.Methods: We performed a longitudinal pilot study and followed 96 inflammation-related proteins over time in serum from patients who underwent surgical treatment of periodontitis (n= 21). The samples were taken before (time 0), and then at 3, 6, and 12 months after surgery. Changes in protein levels were analysed in relation to the clinical outcome measures, that is, proportion of surfaces affected by BOP and PPD. Results: Changes in treatment outcomes with early signs of relapse in periodontitis after surgical treatment, for example, increased BOP and PPDs, were during 12-months follow up associated with increased serum levels of high-sensitivity C-reactive protein (hs-CRP) and programmed death-ligand 1 (PD-L1), and reduced serum levels of cystatin-D protein.Conclusion: This study shows that clinical signs of recurrence of periodontitis after surgery are reflected in serum, but larger studies are needed for verification. Our novel findings of an association between increased PD-L1- and decreased cystatin D-levels and recurrence in periodontitis are interesting because PD-L1 has been shown to facilitate bacterial infections and chronic inflammation and cystatin D to inhibit tissue destruction. Our results justify mechanistic studies regarding the role of these molecules in periodontitis.
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| 5. |
- Isehed, Catrine, et al.
(författare)
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Effectiveness of enamel matrix derivative on the clinical and microbiological outcomes following surgical regenerative treatment of peri-implantitis : A randomized controlled trial
- 2016
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Ingår i: Journal of Clinical Periodontology. - Hoboken, USA : Wiley-Blackwell Publishing Inc.. - 0303-6979 .- 1600-051X. ; 43:10, s. 863-873
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This randomized clinical trial aimed at comparing radiological, clinical and microbial effects of surgical treatment of peri-implantitis alone or in combination with enamel matrix derivative (EMD).Methods: Twenty-six subjects were treated with open flap debridement and decontamination of the implant surfaces with gauze and saline preceding adjunctive EMD or no EMD. Bone level (BL) change was primary outcome and secondary outcomes were changes in pocket depth (PD), plaque, pus, bleeding and the microbiota of the peri-implant biofilm analyzed by the Human Oral Microbe Identification Microarray over a time period of 12 months.Results: In multivariate modelling, increased marginal BL at implant site was significantly associated with EMD, the number of osseous walls in the peri-implant bone defect and a Gram+/aerobic microbial flora, whereas reduced BL was associated with a Gram-/anaerobic microbial flora and presence of bleeding and pus, with a cross-validated predictive capacity (Q(2) ) of 36.4%. Similar, but statistically non-significant, trends were seen for BL, PD, plaque, pus and bleeding in univariate analysis.Conclusion: Adjunctive EMD to surgical treatment of peri-implantitis was associated with prevalence of Gram+/aerobic bacteria during the follow-up period and increased marginal BL 12 months after treatment.
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| 6. |
- Isehed, Catrine, 1958-
(författare)
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Peri-implantitis : treatment and effects of enamel matrix derivative
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biological complications affecting osseointegrated dental implants are a growing treatment problem in clinical practice. Since the number of implant carriers has increased in recent decades, this is an urgent topic in dentistry. Peri-implantitis, inflammatory degradation of the implant-supporting jawbone, affects approximately 20% of all implant carriers and approximately 10% of all implants.Implant surfaces are colonised by microbes that may cause an inflammatory process in the soft tissue around the implant. In some sensitive individuals, the inflammatory response leads to disturbed jawbone remodelling, with increased recruitment and activity of bone-resorbing osteoclasts, which could ultimately lead to implant loss. The corresponding degradation of the bone supporting the teeth is denoted as periodontitis. The current view is that factors such as proinflammatory cytokines and prostaglandins, produced by leukocytes and cells of mesenchymal origin in the inflamed connective tissue, are responsible for local osteoclast recruitment and activation. Pro-inflammatory factors and tissue degradation products will leak into the exudate in the peri-implant sulci and the gingival pockets around the teeth. Analysis of the exudate could be of use for predicting and monitoring peri-implantitis, as well as identifying new targets for treatment.The standard treatment for peri-implantitis is surgery in combination with mechanical cleaning of the implant surface and optimisation of oral hygiene, with the goal of achieving infection control and pocket reduction. This treatment has a moderate effect on healing of the peri-implantitis lesion around the dental implant. The use of adjunctive bone grafts, membranes and antimicrobials has thus far not been shown to achieve a more successful outcome. Adjunctive treatment with enamel matrix derivative (EMD) during regenerative periodontal surgery contributes to wound healing and increased tissue support, but the adjunctive effect of EMD during surgical treatment of peri-implantitis remains unknown.The overall aim of this thesis was to investigate the outcome of a regenerative surgical treatment approach with and without adjunctive EMD treatment from the short- and long-term perspectives and to increase our knowledge of microbial flora and biomarkers in the peri-implant sulci before and after treatment. Furthermore, an additional aim of this work was to investigate whether EMD could directly affect osteoclast formation and activity.We performed a randomised controlled clinical trial of a surgical intervention for peri-implantitis with and without EMD. In multivariate modelling, an increased marginal bone level at the implant site 12 months after surgery was significantly associated with EMD, the number of osseous walls in the peri-implant bone defect and a gram-positive/aerobic microbial flora, whereas a reduced bone level was associated with a gram-negative/anaerobic microbial flora and the presence of bleeding and pus, with a cross-validated predictive capacity (Q2) of 36.4%. Similar trends were observed for bone level, pocket depth, plaque, pus and bleeding, but these associations were statistically non-significant in the univariate analysis. Five years after treatment, no significant differences in bone level changes were observed between groups, but fewer implants were lost to follow-up due to reinfections in the EMD-treated group.We used mass spectrometry to analyse the protein content in peri-implant crevicular fluid (PICF) before and up to 12 months after treatment. The total protein amount and diversity displayed decreasing trends 3, 6 and 12 months after treatment. Multivariate analysis of the PICF protein content revealed two major groups, cluster 2 and cluster 3, of which cluster 2 was associated with an increased risk of implant loss. EMD treatment was associated with cluster 3, which was in turn associated with increased implant survival.To test whether EMD affects osteoclast formation or bone resorption, we added purified EMD to RANKL-stimulated mouse bone marrow macrophage cultures in plastic dishes and counted the number of osteoclasts. We also cultured the cells on bone slices and measured the secretion of TRAP5b and the release of CTX-1 into the culture medium as biomarkers of osteoclast numbers and bone resorption, respectively, but no effect of EMD was observed.In conclusion, adjunctive EMD during surgical treatment of peri-implantitis changed the microbial flora to a less pathogenic microbiota, and similar changes in the inflammatory protein profile of PICF were observed; these effects were associated with implant survival. However, the trend toward a positive healing response after EMD treatment was not associated with a significant radiographic bone gain in this study and needs to be further explored. In addition, our finding that EMD did not affect osteoclast formation or bone resorption in vitro indicates that the effect of EMD on bone regeneration, as seen in periodontitis treatment, does not seem to depend on a direct inhibitory effect on osteoclast formation or bone resorption.
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| 7. |
- Isehed, Catrine, et al.
(författare)
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Surgical treatment of peri-implantitis using enamel matrix derivative, an RCT : 3- and 5-year follow-up
- 2018
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Ingår i: Journal of Clinical Periodontology. - : Wiley-Blackwell. - 0303-6979 .- 1600-051X. ; 45:6, s. 744-753
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the clinical and radiographic outcomes 3 and 5 years after the surgical treatment of peri-implantitis per se or in combination with an enamel matrix derivative (EMD).MATERIALS AND METHODS: At baseline, 29 patients were randomized to surgical treatment with adjunctive EMD or no EMD. One year after the surgical treatment of peri-implantitis, 25 patients remained eligible for survival analyses at the 3- and 5-year follow-up. The primary outcomes were implant loss and bone level (BL) change measured on radiographs, and the secondary outcomes, bleeding on probing, pus and plaque at each implant, were analyzed in 18 and14 patients at the 3- and 5-year follow-up, respectively.RESULTS: After exclusion of 4 patients who discontinued the study, at the 3-year follow-up, 13 (100%) implants survived in the EMD group, and 10 of 12 (83%) in the non-EMD group. At the 5-year follow-up, 11 of 13 (85%) implants in the EMD group and 9 of 12 (75%) in the non-EMD group survived. In multivariate modelling, BL changes and EMD-treatment were positively associated with implant survival. Similarly, the same trend was seen in univariate analysis.CONCLUSIONS: An exploratory analysis suggests that adjunctive EMD is positively associated with implant survival up to five years, but larger studies are needed. This article is protected by copyright. All rights reserved.
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| 8. |
- Lindquist, Susanne, et al.
(författare)
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Enamel matrix derivative does not affect osteoclast formation or bone resorption in cultures of mouse bone marrow macrophages or human monocytes
- 2022
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Ingår i: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 80:7, s. 487-493
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Enamel matrix derivative (EMD) is widely used under the brand name Emdogain® to promote periodontal regeneration in surgical treatment of periodontitis and peri-implantitis. The molecular mechanisms are unclear, but it has been proposed that EMD has stimulatory effects on the root cementum and periodontal ligament cells. Since dental implants lack these structures, we hypothesized that EMD-induced bone gain involve interactions with osteoclast precursor cells, with consequent inhibitory effect on osteoclast formation and/or activity. The aim was to evaluate this hypothesis.Material and methods: Primary mouse bone marrow macrophages (BMMs) and human peripheral blood monocytes were cultured in the presence of receptor activator nuclear factor-κB ligand (RANKL) to stimulate osteoclast formation. A purified Emdogain® fraction was added to the cell cultures and the effect on number and size of newly formed osteoclasts were evaluated. In cultures on natural bone slices, bioanalytical methods were used to assay osteoclast number and bone resorption.Results: EMD had a negative effect on osteoclastogenesis in mouse cultures on plastic surface, whereas addition of EMD to osteoclast precursor cells on bone substrate did not affect osteoclast formation or bone resorption.Conclusions: The results on natural bone matrix contradict a direct effect of EMD on osteoclast precursor cells.
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