Siggelkow, Heide

[["dc.bibliographiccitation.firstpage","45"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Advances in Clinical and Experimental Medicine"],["dc.bibliographiccitation.lastpage","56"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Koepp, Regine"],["dc.contributor.author","Cortis, Julia"],["dc.contributor.author","Komrakova, Marina"],["dc.contributor.author","Schieker, Matthias"],["dc.contributor.author","Hempel, Ute"],["dc.contributor.author","Siggelkow, Heide"],["dc.date.accessioned","2020-12-10T18:42:47Z"],["dc.date.available","2020-12-10T18:42:47Z"],["dc.date.issued","2018"],["dc.description.abstract","BACKGROUND: Crohn´s disease (CD) is associated with a higher prevalence of osteoporosis. The pathogenesis of bone affliction remains controversial, especially if inflammatory cytokines or glucocorticoid therapy are the main contributors. In postmenopausal osteoporosis, bone resorption is induced by IL-6, IL-1β and TNF-α. In contrast, in children with CD, IL-6 exclusively decreased bone formation without affecting bone resorption. OBJECTIVES: The objective of this study was to further clarify the pathophysiology of bone affliction in adult patients with CD with the use of an osteoblast and osteoclast cell model. MATERIAL AND METHODS: Inflammatory cytokines IL-6, IL-1β, and TNF-α were measured in adult CD patients' serum. Mean values of these cytokines were applied with or without dexamethasone to the human cell line SCP-1 (osteoblastic cell model). Also, the effect of cytokines on primary human osteoclast differentiation and activity was determined. RESULTS: The combined cytokine application increased the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratio 2-fold after 2 and 14 days. Additional application of dexamethasone to SCP-1 cells further increased the RANKL/OPG ratio 3-fold, but decreased IL-6 and IL-1β expression to 10% and 50%, respectively. TNF-α expression was maximally suppressed to 16% by dexamethasone in the presence of cytokines. In osteoclasts, the combined cytokine treatment decreased expression of characteristic genes to approx. 30%, while increasing osteoclast resorption activity to 148%. In addition, a cytokine stimulated osteoblast cell culture-generated supernatant stimulated osteoclast resorption activity by 170%. CONCLUSIONS: Our results suggest that IL-6, IL-1β, and TNF-α only in combination induced osteoclaststimulating activity represented by the RANKL/OPG ratio in osteoblasts. Dexamethasone further increased this effect in osteoblasts, while decreasing cytokine expression. The results in osteoclasts support a direct and osteoblast-mediated effect on bone resorption. Our in vitro results differentiate for the first time the effect of cytokines on bone turnover as measured in adult CD patients from the additional dexamethasone effect on osteoblasts as part of the pathophysiology of osteoporosis."],["dc.identifier.doi","10.17219/acem/67561"],["dc.identifier.issn","1899-5276"],["dc.identifier.pmid","29521042"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15197"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78085"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation.issn","1899-5276"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","IL-6, IL-1β, and TNF-α only in combination influence the osteoporotic phenotype in Crohn’s patients via bone formation and bone resorption"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","26"],["dc.bibliographiccitation.journal","Journal of Clinical & Translational Endocrinology"],["dc.bibliographiccitation.lastpage","38"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Koepp, Regine"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Kruppa, Jochen"],["dc.contributor.author","Jung, Klaus"],["dc.contributor.author","Siggelkow, Heide"],["dc.date.accessioned","2019-07-09T11:45:44Z"],["dc.date.available","2019-07-09T11:45:44Z"],["dc.date.issued","2018"],["dc.description.abstract","Background: Crohn's disease (CD) is associated with a higher prevalence of osteoporosis, a complication that is recognized as a significant cause of morbidity. Its pathogenesis is controversial, but the activity of CD is one contributing factor. Methods: We stimulated SCP-1 cells (mesenchymal stem cell line) under osteogenic conditions with serum from adult patients with CD in the symptomatic phase (SP) and in remission (R) and with control sera. Concentrations of IL-6, IL-1 beta, and TNF alpha in the sera were measured. Patients were classified as normal or osteopenic/osteoporotic based on bone mineral density (BMD) T-score measurements. After 14 days in culture, protein expression and gene ontology (GO) annotation analysis was performed. Results: Cytokine concentrations (IL-6, IL-1 beta, TNF alpha) varied within sera groups. None of the cytokines were significantly increased in the symptomatic phase compared to remission. Protein analysis revealed 17 proteins regulated by the SP versus R phase sera of disease. A linear relationship between CDAI (Crohn's disease activity index) and normalized protein expression of APOA1 and 2, TTR, CDKAL1 and TUBB6 could be determined. Eleven proteins were found to be differentially regulated comparing osteoporosis-positive and osteoporosis-negative sera. Gene annotation and further analysis identified these genes as part of heme and erythrocyte metabolism, as well as involved in hypoxia and in endocytosis. A significant linear relationship between bone mineral density and normalized protein expression could be determined for proteins FABP3 and TTR. Conclusion: Our explorative results confirm our hypothesis that factors in serum from patients with CD change the protein expression pattern of human immortalized osteoblast like cells. We suggest, that these short time changes indeed influence factors of bone metabolism."],["dc.identifier.doi","10.1016/j.jcte.2018.06.002"],["dc.identifier.pmid","30003044"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15299"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59299"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2214-6237"],["dc.rights","CC BY-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Crohn's disease patient serum changes protein expression in a human mesenchymal stem cell model in a linear relationship to patients' disease stage and to bone mineral density"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]