Siggelkow, Heide

[["dc.bibliographiccitation.journal","Journal of Bone and Mineral Research"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Kluever, A."],["dc.contributor.author","Ponce, M. L."],["dc.contributor.author","Hufner, M."],["dc.contributor.author","Siggelkow, Heide"],["dc.date.accessioned","2018-11-07T10:45:16Z"],["dc.date.available","2018-11-07T10:45:16Z"],["dc.date.issued","2004"],["dc.format.extent","S270"],["dc.identifier.isi","000224326801438"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47469"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Bone & Mineral Res"],["dc.publisher.place","Washington"],["dc.relation.conference","26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research"],["dc.relation.eventlocation","Seattle, WA"],["dc.relation.issn","0884-0431"],["dc.title","Expression of the Human Urea Transporter HUT11 in comparison to the adipogenic marker aP2 in subpopulations of primary human osteoblasts"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","570"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Bone"],["dc.bibliographiccitation.lastpage","576"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Schmidt, E."],["dc.contributor.author","Hennies, B."],["dc.contributor.author","Hufner, M."],["dc.date.accessioned","2018-11-07T10:46:33Z"],["dc.date.available","2018-11-07T10:46:33Z"],["dc.date.issued","2004"],["dc.description.abstract","Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein that was first detected in tumor-induced osteomalacia (TIO). Investigations in mice revealed that MEPE is expressed in bone and teeth in a maturation-dependent manner, reaching its maximum during mineralization. However, from knockout experiments, although it has become clear that MEPE might function as a mineralization inhibitor, the exact mechanism of action is still unclear. Even less is known about the regulation of MEPE in men. Therefore, we have studied the time- and maturation-dependent expression of MEPE in two human osteoblast culture systems, the osteosarcoma cell line HOS 58 and primary trabecular osteoblasts. Cells were cultured for up to 29 days, and the influence of beta-glycerophosphate (bGP), ascorbate, transforming growth factor beta (TGF-beta), BMP-2, and dexamethasone was studied. HOS 58 cells showed no significant effect on MEPE gene expression up to 5.0 mM, but a significant inhibition was revealed at 10 and 20 mM, when osteocalcin (OC) expression was maximal. Under the same conditions, primary human osteoblasts showed no effect on MEPE gene expression. However, when cultured in the presence of 5 mM beta-glycerophosphate, ascorbate, and dexamethasone for 29 days, which are similar conditions to those described by Owen in his differentiation model in rat osteoblasts, a progressive inhibition of MEPE gene expression to 20% of the maximum was observed. Increasing osteocalcin expression indicated advancing differentiation. In conclusion, in contrast to the results in mice, when MEPE was maximally expressed during mineralization, in the human system, this factor seems to be maximally active in the proliferation and early matrix maturation phase. It was, however, strongly suppressed, associated with the mineralization phase. (C) 2004 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.bone.2004.03.033"],["dc.identifier.isi","000223027400029"],["dc.identifier.pmid","15268910"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47773"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.conference","Meeting of the German-Speaking-Societies-of-Osteology"],["dc.relation.eventlocation","Gottingen, GERMANY"],["dc.relation.issn","8756-3282"],["dc.title","Evidence of downregulation of matrix extracellular phosphoglycoprotein during terminal differentiation in human osteoblasts"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Bone"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Eidner, T."],["dc.contributor.author","Lehmann, G."],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Raddatz, Dirk"],["dc.contributor.author","Hein, G."],["dc.contributor.author","Hufner, M."],["dc.date.accessioned","2018-11-07T09:05:34Z"],["dc.date.available","2018-11-07T09:05:34Z"],["dc.date.issued","2001"],["dc.format.extent","S140"],["dc.identifier.isi","000168825000317"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25351"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.issn","8756-3282"],["dc.title","Cytokines, osteoprotegerin and osteoprotegerin-ligand in vitro and histomorphometric indices of bone formation in patients with different bone diseases"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1602"],["dc.bibliographiccitation.issue","30"],["dc.bibliographiccitation.journal","DMW - Deutsche Medizinische Wochenschrift"],["dc.bibliographiccitation.lastpage","1608"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Hufner, M."],["dc.contributor.author","Siggelkow, Heide"],["dc.date.accessioned","2018-11-07T10:37:36Z"],["dc.date.available","2018-11-07T10:37:36Z"],["dc.date.issued","2003"],["dc.identifier.isi","000184373800006"],["dc.identifier.pmid","12884149"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45605"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.relation.issn","0012-0472"],["dc.title","New data on the pathogenesis of steroid-induced osteoporosis: Consequences for therapy and prevention"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","529"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Bone and Mineral Research"],["dc.bibliographiccitation.lastpage","538"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Eidner, T."],["dc.contributor.author","Lehmann, G."],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Raddatz, Dirk"],["dc.contributor.author","Munzel, U."],["dc.contributor.author","Hein, G."],["dc.contributor.author","Hufner, M."],["dc.date.accessioned","2018-11-07T10:40:33Z"],["dc.date.available","2018-11-07T10:40:33Z"],["dc.date.issued","2003"],["dc.description.abstract","Cytokines are supposed to play an essential role in the regulation of the bone metabolic unit. However, information on cytokine production of primary human osteoblasts from patients with metabolic bone disease is scarce, and few attempts have been made to correlate such data to histomorphometric parameters of individual patients. We investigated 11 patients with metabolic bone disease referred to our outpatient department for bone biopsy and analyzed interleukin (IL)-1, IL-6, and TNF-alpha protein release and gene expression in primary osteoblast cultures. Compared with four controls, five patients showed normal cytokine protein release, whereas six patients showed much higher levels of interleukin-6 (26-fold) and TNF-alpha (84-fold). All three cytokines were strongly correlated concerning gene expression and/or protein levels (r = 0.72-0.96). Histomorphometric analysis of the bone samples showed that eroded surface (ES/BS) as a parameter of bone resorption was significantly associated with TNF-alpha. In addition, RANKL gene expression was positively associated with ES/BS and osteoclast surface (Oc.S/BS). Finally, the formation parameters osteold volume and osteoid surface were negatively associated with TNF-alpha. In conclusion, in an in vitro-ex vivo model of bone cells obtained from a group of 11 patients with different forms of metabolic bone disease, cytokine release in conditioned medium was significantly associated with bone resorption and bone formation, as quantified by histomorphometry. TNF-alpha seemed to be the more important cytokine; its effect on bone resorption could be mediated by RANKL."],["dc.identifier.doi","10.1359/jbmr.2003.18.3.529"],["dc.identifier.isi","000181178400018"],["dc.identifier.pmid","12619938"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46326"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Bone & Mineral Res"],["dc.publisher.place","Washington"],["dc.relation.conference","1st Joint Meeting of the International-Bone-and-Mineral-Society/European-Calcified-Tissue-Society"],["dc.relation.eventlocation","MADRID, SPAIN"],["dc.relation.issn","0884-0431"],["dc.title","Cytokines, osteoprotegerin, and RANKL in vitro and histomorphometric indices of bone turnover in patients with different bone diseases"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","205"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Aktuelle Rheumatologie"],["dc.bibliographiccitation.lastpage","212"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Hufner, M."],["dc.contributor.author","Siggelkow, Heide"],["dc.date.accessioned","2018-11-07T08:33:06Z"],["dc.date.available","2018-11-07T08:33:06Z"],["dc.date.issued","2001"],["dc.description.abstract","Controversy continues whether as to and under which conditions fluoride-induced bone is sufficiently stable. The unique selectivity of fluoride ions to induce osteoblast proliferation and matrix synthesis is unquestioned; however, fluoride is accumulated in the newly formed bone in depending on the concentration and, when exceeding a toxic level, deteriorates the mechanical strength by changing the bone crystal structure. In addition, fluorides delay the mineralisation time and, if used above the toxic threshold, induce osteomalacia-like changes which are even worse when calcium deficiency develops. The favourable osteoblast-stimulating effect can be expected in a narrow therapeutic window between 5 and 10 mu mol fluoride while the toxic accumulation in bone increases in linear proposition with the fluoride serum concentration. Hence, sustained-release or retarded sodium fluoride preparations are now preferred which are mainly absorbed in the small bowel and produce fewer gastrointestinal side effects. Another experimental treatment approach used recently is the intermittent application of fluoride. Controlled clinical studies during the last ten years show inconsistent results. Although bone density increased substantially, some controlled studies could not detect a significant effect on the spinal fracture rate. Other studies, however, using low-dose and slow-release preparations or in connection with intermittent, cyclical application with sufficient additional calcium, demonstrated an impressive decrease of the spinal fracture rate in postmenopausal women. In conclusion, several important details of fluoride therapy are still unclear and no standardised therapeutic scheme has been developed so far. Therefore, fluoride does not meet the criteria of evidence-based medicine and continues to be an experimental drug which cannot be recommended for general practice."],["dc.identifier.doi","10.1055/s-2001-18141"],["dc.identifier.isi","000172189000003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17496"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.relation.issn","0341-051X"],["dc.title","Therapy of osteoporosis with fluoride"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","279"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Cellular Biochemistry"],["dc.bibliographiccitation.lastpage","294"],["dc.bibliographiccitation.volume","85"],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Schenck, M."],["dc.contributor.author","Rohde, Manfred"],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Tauber, S."],["dc.contributor.author","Atkinson, M. J."],["dc.contributor.author","Hufner, M."],["dc.date.accessioned","2018-11-07T10:33:19Z"],["dc.date.available","2018-11-07T10:33:19Z"],["dc.date.issued","2002"],["dc.description.abstract","Cultured rodent osteoblastic cells reiterate the phenotypic differentiation and maturation of osteoblasts seen in vivo. As previously shown, the human osteosarcoma cell line HOS 58 represents a differentiated stage of osteoblast development. The potential of HOS 58 for still further in vitro differentiation suggests the line can serve as a model of osteoblast maturation. Using this cell line, we have investigated the influence of 1,25-(OH)(2)-D-3 (D-3), TGF-beta and Dexamethasone (Dex) on proliferation and on the protein and mRNA levels of alkaline phosphatase (AP), procollagen I (Col 1), and osteocalcin (Oc), as well as mineralization during 28 days in culture. AP mRNA and protein were highly expressed throughout the culture period with further increase of protein AP activity at constant gene expression levels. A differentiation inhibiting effect of either TGF-beta or Dex was seen. Col 1 was investigated without the use of ascorbic acid and showed only minor changes during culture time or stimulation. The gene expression for Oc increased continually whereas protein synthesis peaked at confluence and decreased thereafter. TGF-beta and Dex treatments decreased Oc mRNA and protein levels. Stimulation by D3 was maximal at day 7 with a decrease thereafter. HOS 58 cells showed no mineralization capacity when stimulated with different agents, as measured by energy-dispersive X-ray microanalysis. This was not due to absence of Cbfa1 expression. In conclusion, the HOS 58 osteosarcoma cell line represents a differentiated cell line with highly expressed and physiologically regulated AP expression during further differentiation in culture. We observed a dissociation between osteocalcin gene expression and protein secretion which may contribute to the lack of mineralization in this cell line. J. Cell. Biochem. 85: 279-294, 2002. (C) 2002 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/jcb.10122"],["dc.identifier.isi","000174813800006"],["dc.identifier.pmid","11948684"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44581"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0730-2312"],["dc.title","Prolonged culture of HOS 58 human osteosarcoma cells with 1,25-(OH)(2)-D-3, TGF-beta, and dexamethasone reveals physiological regulation of alkaline phosphatase, dissociated osteocalcin gene expression, and protein synthesis and lack of mineralization"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","667"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","DMW - Deutsche Medizinische Wochenschrift"],["dc.bibliographiccitation.lastpage","670"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Harms, E."],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Buchfelder, Michael"],["dc.contributor.author","Saeger, W."],["dc.contributor.author","Hufner, M."],["dc.date.accessioned","2018-11-07T10:39:56Z"],["dc.date.available","2018-11-07T10:39:56Z"],["dc.date.issued","2003"],["dc.identifier.doi","10.1055/s-2003-38281"],["dc.identifier.isi","000181923000003"],["dc.identifier.pmid","12660899"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46174"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.relation.issn","0012-0472"],["dc.title","Macroadenoma of the pituitary gland with moderate hyperprolactinaemia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","467"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","European Journal of Endocrinology"],["dc.bibliographiccitation.lastpage","473"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Melzer, A."],["dc.contributor.author","Nolte, W."],["dc.contributor.author","Karsten, K."],["dc.contributor.author","Hoppner, W."],["dc.contributor.author","Hufner, M."],["dc.date.accessioned","2018-11-07T09:06:03Z"],["dc.date.available","2018-11-07T09:06:03Z"],["dc.date.issued","2001"],["dc.description.abstract","Objective: Booth multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are caused by germline mutations of the RET proto-oncogene. A broad spectrum of malignancy within and between families has been described with no clear genotype-phenotype correlation due to a scarcity of available data of large kindreds. Design: Here we present the only known family with a germline mutation of codon 611 TGC to TTC (exon 10) in the RET proto-oncogene leading to a replacement of cysteine by phenylalanine (Cys611Phe or C611F). Results: Twenty family members of this large kindred are gene carriers (GCs) and seven (5-13 years old) are potential carriers but have yet to be analysed, The clinical course of medullary thyroid carcinoma (MTC) in this family is characterized by a very slow evolution and progression of the tumour with no MTC-related death to date. Of 11 patients (30-69 years old) having undergone thyroidectomy six were classified as pT(1), four as pT(2) and one as C-cell hyperplasia according to the TNM system of the International Union Against Cancer. Due to cervical and mediastinal lymph node metastasis one patient (44 years old) had to be operated on a second time. The seven non-operated GCs of the fourth and fifth generation (17-26 years old) are yearly monitored with pentagastrin stimulation tests; one non-operated GC (43 years old) has refused any further investigations. Screening for primary hyperparathyroidism and phaeochromocytoma was negative in all cases. Conclusion: We suggest from these experiences that the general advice for thyroidectomy in early childhood should be modified in certain families, depending on genotype."],["dc.identifier.doi","10.1530/eje.0.1440467"],["dc.identifier.isi","000168732800004"],["dc.identifier.pmid","11331212"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25469"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bio Scientifica Ltd"],["dc.relation.issn","0804-4643"],["dc.title","Presentation of a kindred with familial medullary thyroid carcinoma and Cys61 1Phe mutation of the RET proto-oncogene demonstrating low grade malignancy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","348"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Cellular Biochemistry"],["dc.bibliographiccitation.lastpage","356"],["dc.bibliographiccitation.volume","86"],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Tauber, S."],["dc.contributor.author","Raddatz, Dirk"],["dc.contributor.author","Schutze, N."],["dc.contributor.author","Hufner, M."],["dc.date.accessioned","2018-11-07T10:33:19Z"],["dc.date.available","2018-11-07T10:33:19Z"],["dc.date.issued","2002"],["dc.description.abstract","Core binding factor alpha 1 (Cbfa1) is air osteoblast-specific transcription factor essential to develop a mature osteoblast phenotype. However, its exact role in the sign a I in g of various osteotropic-differentiating agents is still unclear in this study, we assessed the effects of 1,25-(OH)(2)-D3 (D3), ascorbic acid, bone morphogenetic protein-2 (BMP-2), dexamethasone (Dex), and transforming growth factor-beta (TGF-beta) on Cbfa1 and osteocalcin (OCN) mRNA steady state levels (by semiquantitative RT-PCR) in an in vitro model of osteoblast differentiation. TGF-beta increased Cbfa1 mRNA levels in normal primary human osteoblasts (pHOB) by 2.6-fold in a time-dependent fashion with maximum effect on day 28 (P < 0.001). Similarly, the glucocorticoid Dex enhanced Cbfa1 gene expression by pHOB in a time-dependent fashion by up to 4.6-fold (P < 0.001). In contrast, Dex inhibited OCN gene expression levels by 68% (P < 0.01). Treatment with BMP-2 resulted in an earlier enhancement of Cbfa1 and led to a 4.2-fold increase with a maximum on day 21 (P < 0.001). Ascorbic acid did not modulate Cbfa1 and OCN gene expression, The effect of vitamin D (D3) on Cbfa1 mRNA expression was influenced by the duration of treatment, being inhibitory after 1 h and having a stimulatory effect after 48 h. Time course experiments indicated a stimulatory effect of D3 on Cbfa1 mRNA levels (by 2.5-fold after 48 h; P < 0.01). Analysis of the late cellular differentiation marker osteocalcin revealed that D3 increased OCN gene expression by 1 4-fold (P < 0.001). In conclusion, in normal primary human osteoblasts, the rapid and pronounced increase of OCN after treatment with D3 seems not to be mediated by Cbfa1. These data imply that Cbfa1 gene expression is differentially regulated by various osteoblastic differentiating agents and is dependent on the stage of maturation. (C) 2002 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/jcb.10220"],["dc.identifier.isi","000176690400015"],["dc.identifier.pmid","12112004"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44580"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0730-2312"],["dc.title","Differential regulation of Cbfa1/Runx2 and osteocalcin gene expression by vitamin-D3, dexamethasone, and local growth factors in primary human osteoblasts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]