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C. Morsczeck - One of the best experts on this subject based on the ideXlab platform.
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WNT5A supports viability of senescent human dental follicle cells
Molecular and Cellular Biochemistry, 2019Co-Authors: C. Morsczeck, Anja Reck, Torsten E ReichertAbstract:The Osteogenic differentiation of dental follicle cells (DFCs) is inhibited by the onset of cellular senescence, but the cause for this is largely unknown. Recently it was shown that WNT5a, which is an inductor of the non-canonical WNT pathway, stimulates both cellular senescence and Osteogenic differentiation of different cell types. In this study, we investigated the role of WNT5a for viability and Osteogenic differentiation in human DFCs after the induction of cellular senescence. DFCs were cultivated until the induction of cellular senescence. The induction of cellular senescence was confirmed by β-galactosidase staining, estimation of population doubling time, and slightly telomere length shortening. After induction of cellular senescence, the expression of WNT5A and the potential to induce the Osteogenic differentiation decreased. Inhibition of WNT5A by specific siRNAs had significant effect on the viability of DFCs. Cell proliferation was reduced, whereas both cellular senescence and cell death were increased in DFCs. However, an inhibition of WNT5A did only slightly effect the Osteogenic differentiation of DFCs. Our results suggest that WNT5A supports viability during both cell proliferation and Osteogenic differentiation of DFCs.
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The hedgehog-signaling pathway is repressed during the Osteogenic differentiation of dental follicle cells
Molecular and Cellular Biochemistry, 2017Co-Authors: C. Morsczeck, A. Reck, H. C. BeckAbstract:Dental follicle stem cells (DFCs) are precursor cells of alveolar osteoblasts, and previous studies have shown that the growth factor bone morphogenetic protein (BMP)2 induces the Osteogenic differentiation of DFCs. However, the molecular mechanism down-stream of the induction of the Osteogenic differentiation by BMP2 remains elusive. We investigated therefore the phosphoproteome of DFCs after the induction of the Osteogenic differentiation with BMP2. In this study, phosphoproteins of the hedgehog “off” state were differentially expressed. Further analyses revealed that BMP2 induced the expression of repressors of the hedgehog-signaling pathway such as Patched 1 (PTCH1), Suppressor of Fused (SUFU), and Parathyroid Hormone-Related Peptide (PTHrP). Previous studies suggested that hedgehog proteins induce the Osteogenic differentiation of mesenchymal stem cells via a paracrine pathway. Indian hedgehog (IHH) induced the expression of the Osteogenic transcription factor RUNX2. However, a supplementation of the BMP2-based Osteogenic differentiation medium with IHH did not induce the expression of RUNX2. Moreover, IHH inhibited slightly the ALP activity and the mineralization of Osteogenic-differentiated DFCs. In conclusion, our results suggest that BMP2 inhibits the hedgehog signaling after the induction of the Osteogenic differentiation in DFCs.
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a protein kinase a pka β catenin pathway sustains the bmp2 dlx3 induced Osteogenic differentiation in dental follicle cells dfcs
Cellular Signalling, 2015Co-Authors: Sandra Vialebouroncle, Christoph Klingelhoffer, Tobias Ettl, Torsten E Reichert, C. MorsczeckAbstract:The directed expression of Osteogenic transcription factors via a balanced activation of signaling pathways is an important prerequisite for the development of mineralized tissues. A positive-feedback loop of the BMP2-dependent SMAD signaling pathway and the DLX3 transcription factor (BMP2/DLX3 pathway) directs the Osteogenic differentiation of periodontal precursor cells from the dental follicle (DFCs). However, little is known how this BMP2/DLX3 pathway interacts with other crucial signaling pathways such as the WNT/β-catenin signaling pathway. This study investigated the interaction between the BMP2/DLX3 pathway and the WNT pathway during the Osteogenic differentiation of DFCs. BMP2 induced the WNT/β-catenin pathway in DFCs and phosphorylates β-catenin via protein kinase A (PKA). Moreover, only BMP2 facilitated the binding of LEF1/SMAD4/β-catenin complex to the DLX3 promoter, while an inducer of the canonical WNT pathway, WNT3A, act as an inhibitor. Although WNT3A inhibits the Osteogenic differentiation of DFCs the expression of β-catenin was crucial for both the expression of DLX3 and for the Osteogenic differentiation. In conclusion, while the activation of the canonical WNT pathway inhibits the Osteogenic differentiation of DFCs, β-catenin sustains the BMP2/DLX3-mediated Osteogenic differentiation via the activation of PKA.
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genome wide gene expression profiles of dental follicle stem cells
Acta Odontologica Scandinavica, 2015Co-Authors: Tobias Vollkommer, C. Morsczeck, Martin Gosau, Torsten E Reichert, Oliver Felthaus, Werner GotzAbstract:AbstractObjective. Dental stem cells (SCs) will be increasingly used for bone regeneration in the future. Recently, dental follicle cells (DFCs) from retained human third molars have been isolated and characterized as Osteogenic progenitors. Although these results are promising for regenerative dentistry, molecular processes during Osteogenic differentiation are not yet well understood. Materials and methods. This study compared DFCs before and during Osteogenic differentiation. ALP activity was measured and cells were stained with alizarin red. Real-time RT-PCRs for Osteogenic markers were done. The genome-wide expression profile was evaluated using a microarray. Results. DFCs showed strong mineralization and increased expression of Osteogenic marker genes during Osteogenic differentiation. A microarray analysis showed regulated genes before and in the process of Osteogenic differentiation (day 7). Several regulated genes in DFCs were associated with skeletal development. Bioinformatic analysis revealed ...
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laminin regulates the Osteogenic differentiation of dental follicle cells via integrin α2 β1 and the activation of the fak erk signaling pathway
Cell and Tissue Research, 2014Co-Authors: Sandra Vialebouroncle, Martin Gosau, C. MorsczeckAbstract:Dental follicle cells (DFCs) are ideal for studies concerning the differentiation of dental precursor cells into alveolar osteoblasts and cementoblasts. Previous investigations have suggested that the extracellular matrix (ECM) protein laminin and the ECM receptor integrin-α2/-β1 play regulatory roles during the Osteogenic differentiation of DFCs. Our present data indicate that laminin impairs alkaline phosphatase (ALP) activity following Osteogenic induction while inducing integrin-α2/-β1 expression, Osteogenic differentiation marker elevation, and DFC biomineralization. Integrin-α2/-β1 facilitates the laminin-dependent expression of Osteogenic differentiation markers and the laminin-dependent inhibition of ALP activity. Moreover, these laminin-dependent effects on the Osteogenic differentiation of DFCs can be reversed by the inhibition of the FAK/ERK signaling pathway. Thus, laminin regulates the inhibition of early Osteogenic differentiation markers and the induction of late Osteogenic differentiation markers via integrin-α2/-β1 and the activation of the FAK/ERK signaling pathway.
Marcio Mateus Beloti - One of the best experts on this subject based on the ideXlab platform.
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nanotopography drives stem cell fate toward osteoblast differentiation through α1β1 integrin signaling pathway
Journal of Cellular Biochemistry, 2014Co-Authors: Adalberto Luiz Rosa, Rogerio Bentes Kato, L Castro M S Raucci, Lucas Novaes Teixeira, F S De Oliveira, L S Bellesini, P T De Oliveira, Mohammad Q Hassan, Marcio Mateus BelotiAbstract:The aim of our study was to investigate the osteoinductive potential of a titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs) and the mechanism involved in this phenomenon. Polished Ti discs were chemically treated with H2 SO4 /H2 O2 to yield nanotopography and rat MSCs were cultured under Osteogenic and non-Osteogenic conditions on both nanotopography and untreated polished (control) Ti surfaces. The nanotopography increased cell proliferation and alkaline phosphatase (Alp) activity and upregulated the gene expression of key bone markers of cells grown under both Osteogenic and non-Osteogenic conditions. Additionally, the gene expression of α1 and β1 integrins was higher in cells grown on Ti with nanotopography under non-osteogeneic condition compared with control Ti surface. The higher gene expression of bone markers and Alp activity induced by Ti with nanotopography was reduced by obtustatin, an α1β1 integrin inhibitor. These results indicate that α1β1 integrin signaling pathway determines the osteoinductive effect of nanotopography on MSCs. This finding highlights a novel mechanism involved in nanosurface-mediated MSCs fate and may contribute to the development of new surface modifications aiming to accelerate and/or enhance the process of osseointegration.
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nanotopography drives stem cell fate toward osteoblast differentiation through α1β1 integrin signaling pathway
Journal of Cellular Biochemistry, 2014Co-Authors: Adalberto Luiz Rosa, Rogerio Bentes Kato, L Castro M S Raucci, Lucas Novaes Teixeira, F S De Oliveira, L S Bellesini, P T De Oliveira, Mohammad Q Hassan, Marcio Mateus BelotiAbstract:The aim of our study was to investigate the osteoinductive potential of a titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs) and the mechanism involved in this phenomenon. Polished Ti discs were chemically treated with H2SO4/H2O2 to yield nanotopography and rat MSCs were cultured under Osteogenic and non-Osteogenic conditions on both nanotopography and untreated polished (control) Ti surfaces. The nanotopography increased cell proliferation and alkaline phosphatase (Alp) activity and upregulated the gene expression of key bone markers of cells grown under both Osteogenic and non-Osteogenic conditions. Additionally, the gene expression of α1 and β1 integrins was higher in cells grown on Ti with nanotopography under non-osteogeneic condition compared with control Ti surface. The higher gene expression of bone markers and Alp activity induced by Ti with nanotopography was reduced by obtustatin, an α1β1 integrin inhibitor. These results indicate that α1β1 integrin signaling pathway determines the osteoinductive effect of nanotopography on MSCs. This finding highlights a novel mechanism involved in nanosurface-mediated MSCs fate and may contribute to the development of new surface modifications aiming to accelerate and/or enhance the process of osseointegration. J. Cell. Biochem. 115: 540–548, 2014. © 2013 Wiley Periodicals, Inc.
Adalberto Luiz Rosa - One of the best experts on this subject based on the ideXlab platform.
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nanotopography drives stem cell fate toward osteoblast differentiation through α1β1 integrin signaling pathway
Journal of Cellular Biochemistry, 2014Co-Authors: Adalberto Luiz Rosa, Rogerio Bentes Kato, L Castro M S Raucci, Lucas Novaes Teixeira, F S De Oliveira, L S Bellesini, P T De Oliveira, Mohammad Q Hassan, Marcio Mateus BelotiAbstract:The aim of our study was to investigate the osteoinductive potential of a titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs) and the mechanism involved in this phenomenon. Polished Ti discs were chemically treated with H2 SO4 /H2 O2 to yield nanotopography and rat MSCs were cultured under Osteogenic and non-Osteogenic conditions on both nanotopography and untreated polished (control) Ti surfaces. The nanotopography increased cell proliferation and alkaline phosphatase (Alp) activity and upregulated the gene expression of key bone markers of cells grown under both Osteogenic and non-Osteogenic conditions. Additionally, the gene expression of α1 and β1 integrins was higher in cells grown on Ti with nanotopography under non-osteogeneic condition compared with control Ti surface. The higher gene expression of bone markers and Alp activity induced by Ti with nanotopography was reduced by obtustatin, an α1β1 integrin inhibitor. These results indicate that α1β1 integrin signaling pathway determines the osteoinductive effect of nanotopography on MSCs. This finding highlights a novel mechanism involved in nanosurface-mediated MSCs fate and may contribute to the development of new surface modifications aiming to accelerate and/or enhance the process of osseointegration.
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nanotopography drives stem cell fate toward osteoblast differentiation through α1β1 integrin signaling pathway
Journal of Cellular Biochemistry, 2014Co-Authors: Adalberto Luiz Rosa, Rogerio Bentes Kato, L Castro M S Raucci, Lucas Novaes Teixeira, F S De Oliveira, L S Bellesini, P T De Oliveira, Mohammad Q Hassan, Marcio Mateus BelotiAbstract:The aim of our study was to investigate the osteoinductive potential of a titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs) and the mechanism involved in this phenomenon. Polished Ti discs were chemically treated with H2SO4/H2O2 to yield nanotopography and rat MSCs were cultured under Osteogenic and non-Osteogenic conditions on both nanotopography and untreated polished (control) Ti surfaces. The nanotopography increased cell proliferation and alkaline phosphatase (Alp) activity and upregulated the gene expression of key bone markers of cells grown under both Osteogenic and non-Osteogenic conditions. Additionally, the gene expression of α1 and β1 integrins was higher in cells grown on Ti with nanotopography under non-osteogeneic condition compared with control Ti surface. The higher gene expression of bone markers and Alp activity induced by Ti with nanotopography was reduced by obtustatin, an α1β1 integrin inhibitor. These results indicate that α1β1 integrin signaling pathway determines the osteoinductive effect of nanotopography on MSCs. This finding highlights a novel mechanism involved in nanosurface-mediated MSCs fate and may contribute to the development of new surface modifications aiming to accelerate and/or enhance the process of osseointegration. J. Cell. Biochem. 115: 540–548, 2014. © 2013 Wiley Periodicals, Inc.
Kuender D Yang - One of the best experts on this subject based on the ideXlab platform.
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physical shock wave mediates membrane hyperpolarization and ras activation for osteogenesis in human bone marrow stromal cells
Biochemical and Biophysical Research Communications, 2001Co-Authors: Fengsheng Wang, Chingjen Wang, Hueijen Huang, Hou Chung, Rongfu Chen, Kuender D YangAbstract:Physical shock wave (SW) has shown effectiveness on promotion of bone growth. We have recently demonstrated that SW could promote bone marrow stromal cell differentiation toward osteoprogenitor associated with induction of TGF-beta1. We have further demonstrated that SW-induced membrane hyperpolarization and Ras activation acted an early signal for the osteogenesis in human bone marrow stromal cells. An optimal dose of SW treatment at 0.16 mJ/mm(2) for 500 impulses induced a rapid membrane hyperpolarization in 5 min, activation of Ras in 30 min, and cell proliferation in 2 days. The SW-promoted cell growth was related to osteogenesis as demonstrated by increase of bone alkaline phosphatase activity in 6 days and osteocalcin mRNA expression in 12 days. In support that SW-induced Ras activation mediated osteogenesis of human bone marrow stromal cells, we further demonstrated that transfection of bone marrow stromal cells with a dominant negative Ras mutant (Asn-17 ras(H)) abrogated the SW enhancement of Osteogenic transcription factor (CBFA1) activation, osteocalcin mRNA expression, and bone nodule formations. These results suggest that physical SW promotes bone marrow stromal cell differentiation toward Osteogenic lineage via membrane hyperpolarization, followed by Ras activation and specific Osteogenic transcription factor CBFA1 expression. A link between physical SW and biomembrane perturbation-mediated Ras activation may highlight how noninvasive physical agents could be used to promote fracture healing and to rescue patients with osteoporosis and osteopenic disorders in the future.
Sandra Vialebouroncle - One of the best experts on this subject based on the ideXlab platform.
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a protein kinase a pka β catenin pathway sustains the bmp2 dlx3 induced Osteogenic differentiation in dental follicle cells dfcs
Cellular Signalling, 2015Co-Authors: Sandra Vialebouroncle, Christoph Klingelhoffer, Tobias Ettl, Torsten E Reichert, C. MorsczeckAbstract:The directed expression of Osteogenic transcription factors via a balanced activation of signaling pathways is an important prerequisite for the development of mineralized tissues. A positive-feedback loop of the BMP2-dependent SMAD signaling pathway and the DLX3 transcription factor (BMP2/DLX3 pathway) directs the Osteogenic differentiation of periodontal precursor cells from the dental follicle (DFCs). However, little is known how this BMP2/DLX3 pathway interacts with other crucial signaling pathways such as the WNT/β-catenin signaling pathway. This study investigated the interaction between the BMP2/DLX3 pathway and the WNT pathway during the Osteogenic differentiation of DFCs. BMP2 induced the WNT/β-catenin pathway in DFCs and phosphorylates β-catenin via protein kinase A (PKA). Moreover, only BMP2 facilitated the binding of LEF1/SMAD4/β-catenin complex to the DLX3 promoter, while an inducer of the canonical WNT pathway, WNT3A, act as an inhibitor. Although WNT3A inhibits the Osteogenic differentiation of DFCs the expression of β-catenin was crucial for both the expression of DLX3 and for the Osteogenic differentiation. In conclusion, while the activation of the canonical WNT pathway inhibits the Osteogenic differentiation of DFCs, β-catenin sustains the BMP2/DLX3-mediated Osteogenic differentiation via the activation of PKA.
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laminin regulates the Osteogenic differentiation of dental follicle cells via integrin α2 β1 and the activation of the fak erk signaling pathway
Cell and Tissue Research, 2014Co-Authors: Sandra Vialebouroncle, Martin Gosau, C. MorsczeckAbstract:Dental follicle cells (DFCs) are ideal for studies concerning the differentiation of dental precursor cells into alveolar osteoblasts and cementoblasts. Previous investigations have suggested that the extracellular matrix (ECM) protein laminin and the ECM receptor integrin-α2/-β1 play regulatory roles during the Osteogenic differentiation of DFCs. Our present data indicate that laminin impairs alkaline phosphatase (ALP) activity following Osteogenic induction while inducing integrin-α2/-β1 expression, Osteogenic differentiation marker elevation, and DFC biomineralization. Integrin-α2/-β1 facilitates the laminin-dependent expression of Osteogenic differentiation markers and the laminin-dependent inhibition of ALP activity. Moreover, these laminin-dependent effects on the Osteogenic differentiation of DFCs can be reversed by the inhibition of the FAK/ERK signaling pathway. Thus, laminin regulates the inhibition of early Osteogenic differentiation markers and the induction of late Osteogenic differentiation markers via integrin-α2/-β1 and the activation of the FAK/ERK signaling pathway.
