| 1. |
- Bostrom, E. A., et al.
(författare)
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Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-alpha (TNF-alpha and interleukin-1 beta (IL-1 beta), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-kappa B pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in periodontitis and maybe prevent tooth loss.
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| 2. |
- de Vries, Charlotte, et al.
(författare)
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Antibodies to Porphyromonas gingivalis Are Increased in Patients with Severe Periodontitis, and Associate with Presence of Specific Autoantibodies and Myocardial Infarction
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- There is accumulating data suggesting that periodontitis is associated with increased risk of systemic and autoimmune diseases, including cardiovascular disease, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and there is an unmet need to identify these individuals early. With the periodontal bacteria Porphyromonas gingivalis (Pg) as one of the key drivers of periodontitis, we set out to investigate whether antibodies to Pg virulence factor arginine gingipain (Rgp) could serve as a biomarker for periodontitis patients at increased risk of autoimmunity and systemic disease. We measured serum anti-Rgp IgG in three study populations: PAROKRANK (779 individuals with myocardial infarction (MI); 719 controls), where 557 had periodontitis, and 312 were positive for autoantibodies associated with RA/SLE; the PerioGene North pilot (41 periodontitis; 39 controls); and an SLE case/control study (101 SLE; 100 controls). Anti-Rgp IgG levels were increased in severe periodontitis compared to controls (p < 0.0001), in individuals positive for anti-citrullinated protein antibodies (p = 0.04) and anti-dsDNA antibodies (p = 0.035), compared to autoantibody-negative individuals; and in MI patients versus matched controls (p = 0.035). Our data support longitudinal studies addressing the role of anti-Rgp antibodies as biomarkers for periodontitis patients at increased risk of developing autoimmunity linked to RA and SLE, and mechanisms underpinning these associations.
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| 3. |
- Dyab, Ahed, et al.
(författare)
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Human gingival fibroblasts are a source of B cell-activating factor during periodontal inflammation
- 2024
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Ingår i: Journal of Periodontology. - : John Wiley & Sons. - 0022-3492 .- 1943-3670. ; 95:7, s. 673-681
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Tidskriftsartikel (refereegranskat)abstract
- Background: Host-modulating therapy is a possible treatment for individuals that respond poorly to conventional periodontal therapy. B cells, abundant in periodontitis lesions, require the cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) for survival and maturation. Although mRNA levels of BAFF and APRIL are increased in tissue from periodontitis lesions, it is unknown if periodontal resident cells express BAFF and/or APRIL during periodontal inflammation. In this study, we aim to analyze the expression of BAFF and APRIL in human gingival fibroblasts after stimulation with proinflammatory cytokines. Furthermore, we perform protein analysis in tissues and serum from periodontitis patients and healthy controls.Methods: Human gingival fibroblasts were cultured and stimulated with the proinflammatory cytokines’ tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). The mRNA expression of BAFF and APRIL was analyzed by real-time quantitative polymerase chain reaction (qPCR), and the protein was detected in tissue sections using immune staining. Serum levels of BAFF were analyzed with enzyme-linked immunosorbent assay (ELISA).Results: In gingival fibroblasts, TNF-α upregulated BAFF mRNA, but APRIL was unaffected. IL-1β affected neither BAFF nor APRIL expression. BAFF protein was detected in the oral epithelium and in cells of the underlying connective tissue in periodontitis tissue, and BAFF protein was increased in the serum of periodontitis patients.Conclusion: Periodontal resident cells express BAFF during periodontal inflammation and participate in providing a favorable milieu for the survival and action of B cells.
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| 4. |
- 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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| 5. |
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| 6. |
- Kindstedt, Elin, et al.
(författare)
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Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL
- 2018
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Ingår i: Arthritis & Rheumatology. - : Wiley-Blackwell. - 2326-5191 .- 2326-5205. ; 70:4, s. 508-515
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme‐linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL‐positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL‐positive presymptomatic subjects compared with RANKL‐negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.
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| 7. |
- Kindstedt, Elin, 1991-, et al.
(författare)
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CCL11, a novel mediator of inflammatory bone resorption
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Normal bone homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts is perturbed by inflammation. Inchronic inflammatory disease with disturbed bone remodelling, e.g. rheumatoid arthritis, patients show increased serum levels of the chemokine eotaxin-1 (CCL11). Herein, we demonstrate an inflammatory driven expression of CCL11 in bone tissue and a novel role of CCL11 in osteoclast migration and resorption. Using an inflammatory bone lesion model and primary cell cultures, we discovered that osteoblasts express CCL11 in vivo and in vitro and that expression increased during inflammatory conditions. Osteoclasts did not express CCL11, but the high affinity receptor CCR3 was significantly upregulated during osteoclast differentiation and found to colocalise with CCL11. Exogenous CCL11 was internalised in osteoclast and stimulated the migration of pre-osteoclast and concomitant increase in bone resorption. Our data pinpoints that the CCL11/CCR3 pathway could be a new target for treatment of inflammatory bone resorption.
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| 8. |
- Kindstedt, Elin, et al.
(författare)
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Discovery of Innate Lymphoid Cells in Gingivitis and Periodontitis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- AIM: Innate lymphoid cells (ILCs) are the most recently identified leukocytes of the immune system and these cells are increasingly acknowledged to play important roles in host defence and tissue repair. ILCs can also contribute to inflammatory diseases such as asthma and colitis. We analysed the presence and proportions of the different ILC subsets (ILC1, ILC2 and ILC3) in gingivitis and periodontitis. Furthermore, we investigated if ILCs express nuclear factor kappa-B ligand (RANKL), a cytokine crucial for osteoclast differentiation and bone resorption.MATERIALS AND METHODS: We collected gingivitis and periodontitis soft tissue and characterised ILC subsets including RANKL expression in single cell suspensions using flow cytometry. RESULTS: Although not statistically significant, the total number of ILCs detected was twice as many in periodontitis compared to gingivitis. The majority of ILCs, in both conditions, were ILC1s with a 2.5-fold increase of ILC1s in periodontitis compared to gingivitis. Furthermore, we found RANKL expression exclusively expressed on ILC1s.CONCLUSIONS: Our discovery of the presence of ILCs in gingivitis and periodontitis and concomitant expression of RANKL in ILC1 suggest that these cells may be of importance in periodontal disease. In addition, our findings provide new insights into the field of oral immunology.
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| 9. |
- Kindstedt, Elin, et al.
(författare)
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Innate lymphoid cells are present in gingivitis and periodontitis
- 2019
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Ingår i: Journal of Periodontology. - : Wiley-Blackwell. - 0022-3492 .- 1943-3670. ; 90:2, s. 200-207
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Innate lymphoid cells (ILCs) are the most recently identified leukocytes of the immune system and these cells are increasingly acknowledged to play important roles in host defence and tissue repair. ILCs are also contributors of inflammatory diseases such as asthma and colitis. We analyzed the presence and relative proportions of the different ILC subsets (ILC1, ILC2 and ILC3) in gingivitis and periodontitis. Further, we investigated if ILCs express receptor activator of nuclear factor kappa-B ligand (RANKL), a cytokine crucial for osteoclast differentiation and bone resorption.METHODS: We collected gingivitis and periodontitis soft tissue and characterized ILC subsets including RANKL expression in single-cell suspensions using flow cytometry.RESULTS: ILCs were detected both in gingivitis and periodontitis. The majority of ILCs, in both conditions, were ILC1s. Furthermore, RANKL expression was detected on a fraction of the ILC1s.CONCLUSIONS: Our discovery of the presence of ILCs both in gingivitis and periodontitis and concomitant expression of RANKL on a fraction of the ILC1 population suggest that these cells may be of importance in periodontal disease. In addition, our findings provide a new insight into the field of oral immunology.
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| 10. |
- Kindstedt, Elin, et al.
(författare)
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Marginal jawbone loss is associated with onset of rheumatoid arthritis and is related to plasma level of receptor activator of nuclear factor kappa-B-ligand (RANKL)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- OBJECTIVES: We investigated whether periodontitis, displayed as marginal jawbone loss, preceded onset of symptoms of RA. Furthermore, we analysed plasma levels of receptor activator of nuclear factor kappa-B (RANKL), a cytokine crucial for bone resorption and of anti-citrullinated peptide antibodies (ACPA) in pre-symptomatic individuals compared with controls.METHODS: Marginal jawbone levels were measured on dental radiographs from the premolar/molar regions of the jaws of 176 subjects of whom 93 had developed RA. Of these, 47 had documented radiographs predating symptom onset and for 45 of them sex, age and smoking status referents could be matched. The plasma RANKL concentrations were analysed using ELISA. The receiver operating characteristic curve was used to define the cut-off value.RESULTS: Compared with matched referents, bone loss was significantly higher in never-smoking, pre-symptomatic subjects and increasing levels of bone loss was associated with higher risk to develop subsequent RA (hazard ratio=1.06, 95%CI 1.01, 1.11). No association was found in smokers. In the pre- symptomatic RANKL-positive individuals a significantly higher extent of marginal jawbone loss, and those who were both RANKL- and ACPA positive displayed an even more pronounced jawbone loss.CONCLUSIONS: Marginal jawbone loss preceded clinical onset of symptoms of RA but the difference was only manifested in non-smokers. Moreover, pre- symptomatic RA-individuals, who were RANKL positive, displayed a significantly higher degree of marginal jawbone loss, particularly in ACPA positive individuals.
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