Komrakova, Marina

[["dc.bibliographiccitation.firstpage","443"],["dc.bibliographiccitation.journal","Molecular Therapy - Nucleic Acids"],["dc.bibliographiccitation.lastpage","452"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Hoffmann, Daniel B."],["dc.contributor.author","Gruber, Jens"],["dc.contributor.author","Böker, Kai O."],["dc.contributor.author","Deppe, Delia"],["dc.contributor.author","Sehmisch, Stephan"],["dc.contributor.author","Schilling, Arndt F."],["dc.contributor.author","Lemus-Diaz, Nicolas"],["dc.contributor.author","Komrakova, Marina"],["dc.contributor.author","Schneider, Stefan"],["dc.date.accessioned","2019-07-09T11:45:51Z"],["dc.date.available","2019-07-09T11:45:51Z"],["dc.date.issued","2018"],["dc.description.abstract","Rebalancing of the RANKL/OPG system seems to be an effective treatment strategy in postmenopausal osteoporosis. Here, we evaluate the knockdown of RANKL by in-vivo-delivered siRNA in a rat model of osteoporosis. Virus-like-particles (VLPs) derived from polyoma JC virus were used for delivering RANKL siRNA in ovariectomized (OVX) rats. 48 rats were ovariectomized and treated with either 17β-estradiol (E2), VLPs containing RANKL siRNA (siRANKL), or VLPs containing non-cognate siRNA (siCtrl). All OVX groups were subdivided into the prophylaxis group (PG) and the therapy group (TG). The PG received treatment directly after being OVX for 10 weeks. The TG received treatment 5 weeks after being OVX for 5 weeks. Rats were sacrificed 10 weeks after being OVX. Bone and blood samples were analyzed. E2 and siRANKL showed a significant knockdown of RANKL mRNA. A protein knockdown was observed with E2 and siRANKL in the TG but not in the PG. No distinct improvements in biomechanical and morphological properties of the bones were observed after siRANKL treatment. In the PG, E2 protected the bone structure. We demonstrated successful mRNA and protein knockdown by VLP-mediated RNAi in vivo. Knockdown of membranous RANKL did not result in significant improvements of bone properties in this model of early-stage postmenopausal osteoporosis."],["dc.identifier.doi","10.1016/j.omtn.2018.06.001"],["dc.identifier.pmid","30195781"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15329"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59322"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2162-2531"],["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","Effects of RANKL Knockdown by Virus-like Particle-Mediated RNAi in a Rat Model of Osteoporosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","20"],["dc.bibliographiccitation.journal","The Open Bone Journal"],["dc.bibliographiccitation.lastpage","26"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Komrakova, Marina"],["dc.contributor.author","Stuermer, Ewa K."],["dc.contributor.author","Sturm, Armin"],["dc.contributor.author","Schmelz, Ulrich"],["dc.contributor.author","Tezval, Mohammad"],["dc.contributor.author","Stuermer, Klaus M."],["dc.contributor.author","Sehmisch, Stephan"],["dc.date.accessioned","2019-07-09T11:53:38Z"],["dc.date.available","2019-07-09T11:53:38Z"],["dc.date.issued","2012"],["dc.description.abstract","Daily application of parathyroid hormone (PTH 1-34) is used for treatment of osteoporosis. It was investigated whether orchiectomy-induced osteoporotic changes in spine can be ameliorated by every 48h administration of PTH in aged male rats. Eight-month-old male Sprague-Dawley rats were sham operated (n=24) or orchiectomized (Orx, n=36) and maintained untreated over 12 weeks. Thereafter, both tibia underwent transverse metaphyseal osteotomy (Komrakova et al. 2011, J Endocrinol; 209:9-19) and rats were divided into 5 groups treated s.c. as follows: 1) sham vehicle; 2) sham PTH every 24h (PTH/24h); 3) Orx vehicle; 4) Orx PTH/24h; 5) Orx PTH every 48h (PTH/48h). PTH dosage was 40 􀀁g/kg BW per injection. After 5 weeks, lumbar vertebral bodies were used in computed tomographical, biomechanical, histomorphological, ashing and gene expression analyses. Cortical and trabecular densities, biomechanical properties, serum osteocalcin level increased significantly after PTH treatments in all groups (yield load, sham: 232+17N, sham PTH/24h: 376+12N, Orx: 239+16N, Orx PTH/24h: 324+31N, Orx PTH/48h: 297+17N). Bone inorganic weight enhanced after daily PTH application in Orx rats. Bone gene expression did not differ (P>0.05) among the groups. Both PTH administration regimes (24h and 48h) improved impaired bone structure in osteopenic rats. Every 48h application was less effective, however, it improved bone properties to the level observed in healthy (sham) rats. Considering limitation of daily treatments known in humans, these results may be useful for further clinical studies."],["dc.identifier.doi","10.2174/1876525401204010020"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7843"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60468"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1876-5254"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Efficiency of 48h vs. 24h Injection of Parathyroid Hormone for Amelioration of Osteopenic Spine Properties in Male Rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["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"]]