| 1. |
- Jönsson, Daniel, et al.
(författare)
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Differential effects of estrogen on DNA synthesis in human periodontal ligament and breast cancer cells.
- 2005
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Ingår i: Journal of Periodontal Research. - : Wiley. - 1600-0765 .- 0022-3484. ; 40:5, s. 401-406
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is important to clarify the biological function of the female sex hormones estrogen and progesterone in periodontal ligament cells, as these hormones may affect periodontal health. We have previously shown that human periodontal ligament cells express estrogen receptor beta (ERbeta) but not ERalpha, whereas human breast cancer cells (MCF7) express both ERalpha and ERbeta. Data on progesterone receptor (PgR) expression in human periodontal ligament cells have not been reported. OBJECTIVES: Determine PgR expression in human periodontal ligament and MCF7 cells and to investigate how estrogen affects DNA and collagen synthesis in these two cell types showing different pattern of expression for ERalpha and beta. METHODS: Periodontal ligament cells were obtained from the periodontal ligament of premolars extracted for orthodontic reasons and MCF7 cells from the American Type Culture Collection (ATCC). PgR expression was determined by immunocytochemistry. DNA and collagen synthesis was determined by [(3)H]thymidine and L-[(3)H]proline incorporation, respectively. RESULTS: PgR immunoreactivity was observed in nuclei of MCF7 but not periodontal ligament cells. Treatment with estrogen (17beta-estradiol, E(2)) at physiological concentrations for 24 h stimulated DNA synthesis by more than two times in MCF7 cells, whereas there was no effect on periodontal ligament cell DNA synthesis. The ER blocker ICI 182780 fully reversed the stimulatory effect of E(2). Not only short-term (24 h) but also long-term (5 days) treatment with E(2) lacked effect on DNA synthesis in periodontal ligament cells. Neither periodontal ligament cell viability nor collagen synthesis was affected by E(2) treatment. Identical results were observed in periodontal ligament cells from male and female subjects. CONCLUSIONS: Human MCF7 but not periodontal ligament cells express PgR, suggesting that progesterone via PgR affects MCF7 but not periodontal ligament cells. Further, estrogen stimulates breast cancer MCF7 cell proliferation, whereas it has no effect on proliferation of periodontal ligament cells, probably reflecting cell type specific ER expression pattern in these two cell types.
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| 2. |
- Jönsson, Daniel, et al.
(författare)
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The antimicrobial peptide LL-37 is anti-inflammatory and pro-apoptotic in human periodontal ligament cells
- 2012
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Ingår i: Journal of Periodontal Research. - : John Wiley & Sons. - 0022-3484 .- 1600-0765. ; 3:47, s. 330-335
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: The antimicrobial peptide LL-37 is expressed in periodontal tissue, and variations in LL-37 levels have been associated with periodontal disease. The effects of LL-37 on periodontal ligament cell function have not been described before. Here, we assess anti-inflammatory properties of LL-37 and investigate the effects of LL-37 on cell differentiation, cell proliferation and apoptosis in human periodontal ligament cells. MATERIAL AND METHODS: Periodontal ligament cells were obtained from teeth extracted for orthodontic reasons. Cytokine (interleukin-6) and chemokine (monocyte chemoattractant protein-1) expression was determined by quantitative PCR, cell differentiation by alkaline phosphatase activity, cell proliferation by counting cells in a Bürker chamber, DNA synthesis by incorporation of radiolabeled thymidine and apoptosis by cell morphology and activated caspase 3 quantities. RESULTS: Treatment with 0.1 and 1 μm of LL-37 totally reversed lipopolysaccharide-induced monocyte chemoattractant protein-1 expression and suppressed lipopolysaccharide-induced interleukin-6 expression by 50-70%. LL-37 had no effect on alkaline phosphatase activity. Incubation with 8 μm LL-37 strongly reduced cell number. DNA synthesis was attenuated by about 90% in response to 8 μm LL-37, confirming its antiproliferative effect. Cell morphology was altered in an apoptosis-like fashion in cells treated with 8 μm LL-37. Furthermore, the quantity of activated caspase 3 was increased in cells treated with 1 and 8 μm of LL-37, suggesting apoptosis. CONCLUSION: LL-37 strongly attenuates lipopolysaccharide-induced cytokine and chemokine expression and, in high concentrations, reduces cell proliferation through inhibition of DNA synthesis and by promoting apoptosis in human periodontal ligament cells.
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| 3. |
- Jönsson, Daniel, et al.
(författare)
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The human periodontal ligament cell : a fibroblast-like cell acting as an immune cell
- 2011
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Ingår i: Journal of Periodontal Research. - : John Wiley & Sons. - 0022-3484 .- 1600-0765. ; 46:2, s. 153-157
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Periodontal ligament cells are fibroblast-like cells characterized by collagen production but also possessing some osteoblastic features. In the light of numerous studies presented during recent times, which show that human periodontal ligament cells also produce cytokines and chemokines in response to inflammation promoters, it is reasonable to suggest that periodontal ligament cells play a role as promoters of periodontal inflammation through these mechanisms. MATERIAL AND METHODS: The periodontal ligament, which harbours the periodontal ligament cells, is a part of the attachment apparatus comprised of periodontal ligament cells, extracellular matrix and fibres, attaching the root cement to the alveolar bone. Periodontal ligament cells are in close proximity to bacteria within the plaque and the pocket, and thus these cells are readily accessible to bacterial endotoxins and other promoters of inflammation. RESULTS: Cytokines and chemokines, released by periodontal ligament cells upon stimulation with inflammation promoters, reach the blood vessels easily thanks to rich vascularization of the periodontium stimulating recruitment of white blood cells to the site of inflammation. In addition to classical inflammatory cells, such as leucocytes, macrophages and mast cells, the periodontal ligament cells also contribute to periodontal inflammation via their production and release of cytokines and chemokines. CONCLUSION: Therefore, pharmacological treatment of periodontitis should aim to reduce the release of proinflammatory agents not only from classical inflammatory cells but also from periodontal ligament cells.
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| 4. |
- Nebel, Daniel, et al.
(författare)
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Differential regulation of chemokine expression by estrogen in human periodontal ligament cells
- 2010
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Ingår i: Journal of Periodontal Research. - : John Wiley & Sons. - 0022-3484 .- 1600-0765. ; 45:6, s. 796-802
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: Estrogen modulates inflammatory responses, but the mechanisms involved have not yet been identified. Periodontal ligament (PDL) cells produce chemokines (a group of chemoattractant molecules that recruit leukocytes) and it has been suggested that estrogen modulates periodontal inflammation by regulating the expression of chemokines by PDL cells. Therefore, the objectives of this study were to investigate the regulation of chemokine ligand 2 [CCL2/monocyte chemoattractant protein 1 (MCP-1)], chemokine ligand 3 [CCL3/macrophage inflammatory protein-1α (MIP-1α)] and chemokine ligand 5 (CCL5/RANTES) by estrogen in human PDL cells.Material and Methods: PDL cells were obtained from the PDL of premolars, extracted for orthodontic reasons, from two boys and two girls (16 and 17 years of age). PDL cell CCL2, CCL3 and CCL5 mRNA transcripts were determined by quantitative real-time PCR. The concentrations of CCL2, CCL3 and CCL5 proteins were determined by ELISAs.Results: Treatment with 0.5 μg/mL of lipopolysaccharide (LPS, from Escherichia coli) + 100 nm 17β-estradiol (E2) for 24 h reduced the expression of CCL3 mRNA by about 40% compared to PDL cells treated with LPS alone. Attenuation of CCL3 mRNA was not associated with a decrease in CCL3 protein within 48 h, suggesting a slow turnover of the CCL3 protein. Interindividual differences in the effects of E2 on CCL5 mRNA expression were observed. E2 (100 nm) increased the expression of CCL5 by 40-60% in PDL cells derived from two subjects but reduced the expression of CCL5 by about 30% in cells from another subject. CCL2 mRNA and CCL2 protein were highly expressed, but not regulated by E2. Similar data were observed in cells obtained from both boys and girls.Conclusion: Regulation, by estrogen, of chemokine expression in PDL cells shows a complex pattern involving the down-regulation as well as the up-regulation of chemokines, suggesting that estrogen exerts both anti-inflammatory and proinflammatory effects through these mechanisms.
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| 5. |
- Nebel, Daniel, et al.
(författare)
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Estrogen regulates DNA synthesis in human gingival epithelial cells displaying strong estrogen receptor β immunoreactivity
- 2011
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Ingår i: Journal of Periodontal Research. - : John Wiley & Sons. - 0022-3484 .- 1600-0765. ; 46:5, s. 622-628
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: Estrogen acts via estrogen receptor (ER) α and β. The expression pattern of ERs and their importance in gingival tissues are not fully understood. In this study, we investigate gingival ER expression and effects of estrogen on gingival epithelial cell proliferation.Material and Methods: Gingival biopsies were obtained from both healthy and diseased sites in three male and three female subjects. Expression of ERα and β was determined by immunohistochemistry. Effects of 17β-estradiol (E 2) on cell proliferation, monitored by measuring DNA synthesis, were studied in cultured human gingival epithelial HGEPp.05 cells.Results: Estrogen receptorβ, but not ERα, immunoreactivity was demonstrated in nuclei of epithelial cells in all layers of the gingival epithelium, but also in cells of the lamina propria. No differences were observed between male and female subjects. The same pattern, i.e. high ERβ expression but no ERα expression, was observed in both healthy and diseased sites within each individual. No differences in the intensity of the ERβ immunoreactive signal and the number of ERβ-positive nuclei were observed between healthy and diseased gingiva. Treatment with a physiological concentration of E 2 (10nm) had no effect on DNA synthesis in ERβ- and ERα-expressing HGEPp.05 cells. In contrast, E 2 at high concentrations (500nm and 10μm) reduced DNA synthesis by 60-70%.Conclusion: Human gingival epithelial cells display strong ERβ but low ERα immunoreactivity both in vivo and in culture. Estrogen attenuates gingival epithelial cell DNA synthesis at high but not low concentrations, suggesting a concentration-dependent mechanism.
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| 6. |
- Olofsson, A, et al.
(författare)
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Relationship between fibrinolytic activity and gingival inflammatory reaction in young individuals
- 2003
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Ingår i: Journal of Periodontal Research. - : Wiley. - 1600-0765 .- 0022-3484. ; 38:1, s. 104-108
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Tidskriftsartikel (refereegranskat)abstract
- The fibrinolytic system (the plasminogen activating system) is involved in several physiological and pathological processes. Through the transformation of plasminogen to the aggressive broad spectrum protease plasmin, potent enzymatic activity is released. Plasmin acts directly on connective tissue components, and indirectly by activating proforms of the metalloproteinases. The destructive potential of the fibrinolytic system may thus be of importance for the initiation and progression of periodontal diseases. Earlier studies have shown high concentrations of the plasminogen activator t-PA and its inhibitor PAI-2 in gingival crevicular fluid (GCF) as well as enhanced concentrations in areas of gingival inflammation. The aim of this study was to investigate a possible relationship between the gingival inflammatory reactivity and the fibrinolytic activity in gingival crevicular fluid. Thirty-one young individuals took part in the study. Gingival Index scores and Plaque Index scores were assessed and used to formulate a score expressing an individuals' inflammatory response to microbial plaque levels (Relative G/P score). The fibrinolytic activity of GCF was assessed with a fibrin gel lysis assay, and the levels of t-PA and PAI-2 were assayed with ELISAs. All samples showed fibrinolytic activity. A positive correlation between the fibrinolytic activity and Relative G/P score was found. Thus, in individuals with an enhanced reactivity to dental plaque, a higher plasminogen activating activity in GCF was seen. This indicates a higher potential for tissue proteolysis in these individuals, possibly facilitating spread and deeper involvement of the lesions.
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| 7. |
- Dahlén, Gunnar, 1944, et al.
(författare)
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Predominant bacterial species in subgingival plaque in dogs.
- 2012
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Ingår i: Journal of periodontal research. - : Wiley. - 1600-0765 .- 0022-3484. ; 47:3, s. 354-364
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Tidskriftsartikel (refereegranskat)abstract
- Dahlén G, Charalampakis G, Abrahamsson I, Bengtsson L, Falsen E. Predominant bacterial species in subgingival plaque in dogs. J Periodont Res 2011; doi: 10.1111/j.1600-0765.2011.01440.x.©2011 John Wiley & Sons A/S Background and Objective: The dog has been used extensively for experimental and microbiological studies on periodontitis and peri-implantitis without detailed knowledge about the predominant flora of the subgingival plaque. This study was designed to evaluate the predominant cultivable bacterial species in dogs and compare them phenotypically and genotypically with corresponding human species. Material and Methods: Four subgingival samples were taken from two upper premolars in each of six Labrador retrievers. The samples from each dog were processed for anaerobic culture. From the samples of each dog, the five or six predominating bacteria based on colony morphology were selected and pure cultured. Each of the strains was characterized by Gram stain, anaerobic/aerobic growth and API-ZYM test. Eighteen strains showing clear-cut phenotypic differences were further classified based on DNA sequencing technology. Cross-reactions of DNA probes from human and dog strains were also tested against a panel of both human and dog bacterial species. Results: Thirty-one strains in the dogs were isolated and characterized. They represented 21 different species, of which six belonged to the genus Porphyromonas. No species was found consistently in the predominant flora of all six dogs. Porphyromonas crevioricanis and Fusobacterium canifelinum were the two most prevalent species in predominant flora in dogs. DNA probes from human and dog species cross-reacted to some extent with related strains from humans and dogs; however, distinct exceptions were found. Conclusion: The predominant cultural subgingival flora in dogs shows great similarities with the subgingival bacteria from humans at the genus level, but distinct differences at the species level; however, a genetic relatedness could be disclosed for most strains investigated.
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| 8. |
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| 9. |
- Brage, Monica, et al.
(författare)
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Humoral immune response to Aggregatibacter actinomycetemcomitans leukotoxin
- 2011
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Ingår i: Journal of Periodontal Research. - : Wiley. - 0022-3484 .- 1600-0765. ; 46:2, s. 170-175
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: Periodontal disease is an inflammatory condition caused by bacterial infections that result in loss of the tooth supporting tissue. The periodontal pathogens produce virulence factors with capacity to affect the host immune response. Aggregatibacter actinomycetemcomitans is a periodontal pathogen that produces a leukotoxin that specifically affects human leukocytes. The aims of the present study were to examine the presence and function of systemic antibodies to the leukotoxin. Material and Methods: One hundred and ninety-seven middle-aged (57 ± 5 years) Swedes with well-documented periodontal status and medical factors related to cardiovascular diseases were studied. These data have been published previously. The serum samples were examined for the presence of leukotoxin antibodies by western blot and the capacity to neutralize leukotoxicity in an activity assay with leukotoxin and cultured leukemic cells. Results: The results showed a high prevalence (57%) of antibodies against A. actinomycetemcomitans leukotoxin in the analyzed population. These antibodies were correlated with leukotoxin neutralizing capacity as well as with the ELISA titers of A. actinomycetemcomitans-specific IgA and IgG. In addition, high levels of leukotoxin antibodies were correlated with increasing age, but not with periodontal disease parameters or cardiovascular risk factors. Conclusion: Systemic antibodies against A. actionmycetemcomitans leukotoxin were common in this adult Swedish population. These antibodies might contribute to limit the systemic effects of the infection.
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| 10. |
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