Siggelkow, Heide

[["dc.bibliographiccitation.firstpage","214"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cells Tissues Organs"],["dc.bibliographiccitation.lastpage","227"],["dc.bibliographiccitation.volume","170"],["dc.contributor.author","Frosch, Karl-Heinz"],["dc.contributor.author","Barvencik, F."],["dc.contributor.author","Lohmann, Christoph H."],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Breme, J."],["dc.contributor.author","Dresing, Klaus"],["dc.contributor.author","Sturmer, K. M."],["dc.date.accessioned","2018-11-07T10:32:53Z"],["dc.date.available","2018-11-07T10:32:53Z"],["dc.date.issued","2002"],["dc.description.abstract","The goal of this study was to characterize growth, mineralization and bone formation of osteoblast-like cells in titanium pore channels of defined diameter. Titanium implants with continuous drill channels of diameters of 300, 400, 500, 600 and 1,000 mum were inserted into human osteoblast-like cell cultures. The ingrowth of the cells into the drill channels was investigated by transmitted-light microscopy and scanning electron microscopy. Immunofluorescence and histological analysis of 15-channel sections of each diameter were used to investigate the growth behavior and the matrix protein patterns. Mineralization was evidenced by Alizarin red staining and high-resolution microradiography. The ingrowth of human osteoblast-like cells in the drill channels occurred in a sequence of four characteristic stages. In stage 1, osteoblast precursor cells adhered to the wall of the channel and migrated three-dimensionally into the channel by forming foot-like protoplasmic processes. For all 15 sample drill channels that were investigated, the cell ingrowth over 20 days amounted on average to 793 mum (+/- 179) into 600-mum-diameter channels, where they migrated significantly faster than in all the other channels. In stage 2, approximately on day 5-7, the osteoblast-like cells began to anchor on the substrate wall by matrix proteins and to build up a dense network of matrix proteins in the drill channel. The mineralization of the extracellular matrix, while depending on cell stimulation, was initiated in stage 3, on average after 4 weeks. In drill channels of a diameter of 1,000 mum the cell growth was incomplete and no mineralization was found by radiological assessment. Starting in week 6, in the drill channels of diameters ranging from 300 to 600 mum, the network of extracellular matrix proteins and osteoblast-like cells began to form an osteon-like structure. Neither the highly developed migration behavior of osteoblastic cells nor the reorganization from a fiber-like matrix to a lamellar structure have so far been described for cell cultures."],["dc.identifier.doi","10.1159/000047925"],["dc.identifier.isi","000174840400002"],["dc.identifier.pmid","11919409"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44464"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.relation.issn","1422-6405"],["dc.title","Migration, matrix production and lamellar bone formation of human osteoblast-like cells in porous titanium implants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","28"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Cellular Biochemistry"],["dc.bibliographiccitation.lastpage","40"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Pannem, Rajeswararao"],["dc.contributor.author","Braulke, Thomas"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Kuebler, Bernd"],["dc.date.accessioned","2018-11-07T10:59:07Z"],["dc.date.available","2018-11-07T10:59:07Z"],["dc.date.issued","2007"],["dc.description.abstract","The insulin-like growth factors I and II (IGF-I, IGF-II), their receptors, and high affinity binding proteins (IGFBPs) represent a family of cellular modulators that play essential roles in the development and differentiation of cells and tissues including the skeleton. Recently, the human osteosarcoma cell line HOS 58 cells were used as an in vitro model of osteoblast differentiation characterized by (i) a rapid proliferation rate in low-density cells that decreased continuously with time of culture and (ii) an increasing secretion of matrix proteins during their in vitro differentiation. In the present paper, HOS 58 cells with low cell density at early time points of the in vitro differentiation (i) displayed a low expression of IGF-I and -II; (ii) synthesized low levels of IGFBP-2, -3, -4, and -5, but (iii) showed high expression levels of both the type I and II IGF receptors. During the in vitro differentiation of HOS 58 cells, IGF-I and -II expressions increased continuously in parallel with an upregulation of IGFBP-2, -3, -4, and -5 whereas the IGF-I receptor and lGF-II/M6P receptor mRNA were downregulated. in conclusion, the high proliferative activity in low cell density HOS 58 cells was associated with high mRNA levels of the IGF-IR, but low concentrations of IGFBP-2. The rate of proliferation of HOS 58 cells continuously decreased during cultivation in parallel with a decline in IGF-IR expression, but increase of mitoinhibitory IGFBP-2. These data are indicative for a role of the IGF axis during the in vitro differentiation of HOS 58 cells. J. Cell. Biochem. 102: 28-40, 2007. (C) 2007 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/jcb.21274"],["dc.identifier.isi","000249263100003"],["dc.identifier.pmid","17372931"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50624"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0730-2312"],["dc.title","Alteration of the insulin-like growth factor axis during in vitro differentiation of the human osteosarcoma cell line HOS 58"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","725"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Cellular Biochemistry"],["dc.bibliographiccitation.lastpage","735"],["dc.bibliographiccitation.volume","84"],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Grundker, Carsten"],["dc.contributor.author","Blaschke, S."],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Emons, G."],["dc.contributor.author","Hofbauer, L. C."],["dc.date.accessioned","2018-11-07T10:33:20Z"],["dc.date.available","2018-11-07T10:33:20Z"],["dc.date.issued","2002"],["dc.description.abstract","The anti-resorptive effects of estrogen on bone metabolism are thought to be mediated through modulation of paracrine factors produced by osteoblastic lineage cells that act on osteoclastic lineage cells. Receptor activator of nuclear factor-kappaB ligand (RANKL) is the essential factor for osteoclast formation and activation and enhances bone resorption. By contrast, osteoprotegerin (OPG), which is produced by osteoblastic lineage cells acts as a decoy receptor that neutralizes RANKL and prevents bone loss. Recently, 17beta-estradiol was found to stimulate OPG mRNA levels and protein secretion in a human osteoblastic cell line through activation of the estrogen receptor (ER)-alpha. In this study, we assessed the effects of the phytoestrogen genistein on OPG mRNA steady state levels (by semiquantitative RT-PCIR and Northern analysis) and protein production (by ELISA) in primary human trabecular osteoblasts (hOB) obtained from healthy donors. Genistein increased OPG mRNA levels and protein secretion by hOB cells by up to two- to six-fold in a dose- (P< 0.0001) and time-dependent (P< 0.0001) fashion with a maximum effect at 10(-7) M. Co-treatment with the pure ER antagonist ICI 182,780 completely abrogated the stimulatory effects of genistein on OPG protein secretion, indicating that these effects were specific and directly mediated through the ER. Pre-treatment with genistein partially prevented the inhibitory effects of the glucocorticoid dexamethasone on OPG mRNA and protein production. The stimulation of OPG mRNA levels by genistein was not affected by the protein synthesis inhibitor, cycloheximide and was shown to be due to enhancement of OPG gene transcription. In conclusion, our data suggest that the phytoestrogen genistein is capable of upregulating the production of OPG by human osteoblasts. Thus, dietary sources of phytoestrogens may help to prevent bone resorption and bone loss by enhanced osteoblastic production of OPG. (C) 2002 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/jcb.10087"],["dc.identifier.isi","000173618800008"],["dc.identifier.pmid","11835398"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44583"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0730-2312"],["dc.title","Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts"],["dc.type","journal_article"],["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","4206"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","The Journal of Clinical Endocrinology & Metabolism"],["dc.bibliographiccitation.lastpage","4213"],["dc.bibliographiccitation.volume","88"],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Grundker, Carsten"],["dc.contributor.author","Blaschke, S."],["dc.contributor.author","Niederkleine, B."],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Frosch, Karl-Heinz"],["dc.contributor.author","Raddatz, Dirk"],["dc.contributor.author","Emons, G."],["dc.contributor.author","Hofbauer, L. C."],["dc.date.accessioned","2018-11-07T10:36:37Z"],["dc.date.available","2018-11-07T10:36:37Z"],["dc.date.issued","2003"],["dc.description.abstract","Raloxifene reduces bone loss and prevents vertebral fractures in postmenopausal women. Its skeletal effects are mediated by estrogen receptors ( ER) and their modulation of paracrine osteoblastic factors. Receptor activator of nuclear factor-kappaB ligand is essential for osteoclasts and enhances bone resorption, whereas osteoprotegerin (OPG) neutralizes receptor activator of nuclear factor-kappaB ligand. Here, we assessed the effects of raloxifene on OPG production in human osteoblasts (hOB). Raloxifene enhanced gene expression of ER-alpha and progesterone receptor. Moreover, raloxifene increased OPG mRNA levels and protein secretion by hOB in a dose- and time-dependent fashion by 2- to 4-fold with a maximum effect at 10(-7) M and after 72 h ( P < 0.001). Treatment with the ER antagonist ICI 182,780 abrogated the effects of raloxifene on OPG production. Moreover, raloxifene enhanced osteoblastic differentiation markers, type 1 collagen secretion, and alkaline phosphatase activity by 3- and 2-fold, respectively ( P < 0.001). In addition, raloxifene inhibited expression of the bone-resorbing cytokine IL-6 by 25 - 45% ( P < 0.001). In conclusion, our data suggest that raloxifene stimulates OPG production and inhibits IL-6 production by hOB. Because OPG production increases with osteoblastic maturation, enhancement of OPG production by raloxifene could be related to its stimulatory effects on osteoblastic differentiation."],["dc.identifier.doi","10.1210/jc.2002-021877"],["dc.identifier.isi","000185258700031"],["dc.identifier.pmid","12970288"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45369"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Endocrine Soc"],["dc.relation.issn","0021-972X"],["dc.title","Raloxifene concurrently stimulates osteoprotegerin and inhibits interleukin-6 production by human trabecular osteoblasts"],["dc.type","journal_article"],["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.journal","Journal of Bone and Mineral Research"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Gruendker, Carsten"],["dc.contributor.author","Blaschke, S."],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Emons, G."],["dc.contributor.author","Hofbauer, L. C."],["dc.date.accessioned","2018-11-07T08:42:58Z"],["dc.date.available","2018-11-07T08:42:58Z"],["dc.date.issued","2001"],["dc.format.extent","S259"],["dc.identifier.isi","000170709000501"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19832"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Bone & Mineral Res"],["dc.publisher.place","Washington"],["dc.relation.issn","0884-0431"],["dc.title","The phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts."],["dc.type","conference_abstract"],["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","68"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Immunobiology"],["dc.bibliographiccitation.lastpage","81"],["dc.bibliographiccitation.volume","202"],["dc.contributor.author","Heinemann, Dagmar E.H."],["dc.contributor.author","Siggelkow, Heide"],["dc.contributor.author","Ponce, Laura M."],["dc.contributor.author","Viereck, Volker"],["dc.contributor.author","Wiese, Karl G."],["dc.contributor.author","Peters, J. Hinrich"],["dc.date.accessioned","2021-06-01T10:50:12Z"],["dc.date.available","2021-06-01T10:50:12Z"],["dc.date.issued","2000"],["dc.description.abstract","Human monocytes (Mo) in culture can be differentiated into macrophages (M phi), dendritic cells (DC) and osteoclasts. In addition, we have established a Mo-derived in vitro granuloma model which here was compared with ex-vivo isolated foreign body granuloma cells. In these models overlapping phenotypes developed between monocyte-derived dendritic cells (MoDC), osteoclasts, M phi, and osteoblasts. In Mo cultures granulomas were induced by immobilized particulate material. AP activity (osteoblast marker) was found to be co-expressed with cytoplasmic tartrate resistant acid phosphatase (TRAP) as a marker of osteoclasts. While proliferating, the number of AP(+) cells decreased, being replaced by cells co-expressing the osteoclast markers vitronectin receptor (VNR) and TRAP. Coexpression of the Mo/M phi marker CD68 with AP or VNR confirmed the monocytic origin of the cells. When Mo were treated with interleukin-4 (IL-4), the number of AP(+) cells markedly increased and remained stably expressed over 12 days. In explants from ex vivo granulomas obtained from endoprosthetic revisions the major cell type was the AP(+) cell co-expressing CD68. The bone-specific alkaline phosphatase (BAP) as a marker of osteoblasts was detected by FAGS analysis in the ex vivo granuloma cells. By RT-PCR the mRNA for osteocalcin, which is a highly specific marker fur osteoblasts, was detected. From our results we conclude an ontogenetic relationship between macrophages, DC and osteoclasts. Furthermore, the data suggest a transdifferentiation between Mo and osteoblasts."],["dc.identifier.doi","10.1016/S0171-2985(00)80054-6"],["dc.identifier.isi","000087597600010"],["dc.identifier.pmid","10879691"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86569"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Gustav Fischer Verlag"],["dc.publisher.place","Jena"],["dc.relation.conference","Conference on Definition of Human Blood Monocytes"],["dc.relation.eventlocation","MUNICH, GERMANY"],["dc.relation.issn","0171-2985"],["dc.title","Alkaline Phosphatase Expression during Monocyte Differentiation Overlapping markers as a link between monocytic cells, dendritic cells, osteoclasts and osteoblasts"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["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"]]