The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Kristi S Anseth - One of the best experts on this subject based on the ideXlab platform.
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the effect of heparin functionalized peg hydrogels on three dimensional human mesenchymal stem cell Osteogenic Differentiation
Biomaterials, 2007Co-Authors: Danielle S W Benoit, Andrew R Durney, Kristi S AnsethAbstract:Poly(ethylene glycol) (PEG) hydrogels functionalized with heparin were utilized as a three-dimensional culture system for human mesenchymal stem cells (hMSCs). Heparin-functionalized hydrogels supported hMSC viability, as quantified through live/dead imaging, and induced Osteogenic Differentiation, as measured by increased alkaline phosphatase (ALP) production and osteopontin (OPN) and collagen I (COL I) gene expression over the 5-week study. Further exploration of the potential mechanism of heparin-induced Osteogenic Differentiation was performed. Specifically, the availability of bone morphogenetic protein 2 (BMP2) and fibronectin (FN) in the culture system was controlled and hMSC Osteogenic Differentiation was evaluated as a function of the microenvironment. BMP2 availability increased both ALP production and OPN gene expression, while FN increased ALP production, but not OPN gene expression. Furthermore, immunostaining of integrin expression revealed that viability and Differentiation were differentially affected by integrin production, where both alpha5beta1 and alphavbeta3 integrin-ligand interactions supported viability, while only the alpha5beta1 integrin played a role in hMSC Osteogenic Differentiation.
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in vitro Osteogenic Differentiation of human mesenchymal stem cells photoencapsulated in peg hydrogels
Journal of Biomedical Materials Research Part A, 2004Co-Authors: Charles R Nuttelman, Kristi S Anseth, Margaret C TripodiAbstract:Much research has focused on the Differentiation of human mesenchymal stem cells (hMSCs) in monolayer culture; however, little is known about their Differentiation potential in three-dimensional culture conditions. In this research, hMSCs were encapsulated in a photocrosslinkable, injectable scaffolding system based on poly(ethylene glycol) (PEG) hydrogels. To demonstrate the ability of hMSCs to differentiate in PEG hydrogels, cell/polymer constructs were cultured in Osteogenic Differentiation media to elicit an osteoblastic response. First, viability of encapsulated hMSCs up to 4 weeks in culture was investigated using a membrane integrity assay. Second, gene expression of encapsulated cells was determined with reverse transcription polymerase chain reaction (RT-PCR) as a function of media composition. After 1 week in Osteogenic Differentiation media, encapsulated hMSCs expressed osteonectin, osteopontin, and alkaline phosphatase, which are all characteristic of osteoblasts. Finally, von Kossa staining was used to evaluate mineralization of the PEG gels. Results support the hypothesis that hMSCs photoencapsulated in PEG hydrogels and cultured in the presence of Osteogenic Differentiation media are able to differentiate to osteoblasts inside the gel and mineralize the matrix. These experiments demonstrate the feasibility of using a PEG-based, photocrosslinkable system to culture and deliver human mesenchymal stem cells for bone tissue regeneration and repair.
C. Morsczeck - One of the best experts on this subject based on the ideXlab platform.
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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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zbtb16 induces Osteogenic Differentiation marker genes in dental follicle cells independent from runx2
Journal of Periodontology, 2014Co-Authors: Oliver Felthaus, Martin Gosau, C. MorsczeckAbstract:Background: Dental follicle cells (DFCs) are neural crest cell–derived cells and the genuine precursor cells of cementoblast and alveolar osteoblasts. After Osteogenic Differentiation, expression levels of the transcription factor zinc factor and BTB domain containing 16 (ZBTB16) were significantly increased. ZBTB16 is associated with the process of Osteogenic Differentiation in bone marrow–derived mesenchymal stem cells and crucial for the expression of the Osteogenic transcription factor runt-related transcription factor 2 (RUNX2). It is proposed that ZBTB16 plays also a crucial role for the Differentiation of DFCs into osteoblasts.Methods: In this study, the Differentiation of DFCs by alkaline phosphatase (ALP) activity measurement, alizarin red staining, and electron-dispersive x-ray spectrometry (EDX) analysis is investigated. The expression of ZBTB16 during Osteogenic Differentiation and the expression of Osteogenic Differentiation markers were assessed by real-time reverse transcription polymerase ...
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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.
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notch1 signaling regulates the bmp2 dlx 3 directed Osteogenic Differentiation of dental follicle cells
Biochemical and Biophysical Research Communications, 2014Co-Authors: Sandra Vialebouroncle, Martin Gosau, C. MorsczeckAbstract:Dental follicle cells (DFCs) are dental stem/progenitor cells and the genuine precursors of alveolar osteoblasts and dental cementoblasts. A previous study showed that the transcription factor DLX3 (distal less homeobox 3) supports the Osteogenic Differentiation in DFCs via a positive feedback loop with the bone morghogenetic protein (BMP) 2. Until today, however, the control of this BMP2/DLX3 pathway by additional signaling pathways remains elusive. Previous studies also suggested that the NOTCH signaling pathway plays a role in the Osteogenic Differentiation of DFCs. In this study we showed that DLX3 overexpression and the initiation of the Osteogenic Differentiation by BMP2 or dexamethasone induced the NOTCH signaling pathway in DFCs. However, the induction of NOTCH-signaling impaired not only the Osteogenic Differentiation (ALP activity and mineralized nodules) but also the expression of the transcription factor DLX3 and the activation of the BMP-signaling pathway. So, NOTCH signaling plays a regulatory role for the Osteogenic Differentiation of DFCs. In conclusion, results of our study suggest that the NOTCH-signaling pathway, which is activated during the Osteogenic Differentiation of DFCs, regulates the BMP2/DLX3 directed Differentiation of DFCs via a negative feed-back loop.
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.
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notch1 signaling regulates the bmp2 dlx 3 directed Osteogenic Differentiation of dental follicle cells
Biochemical and Biophysical Research Communications, 2014Co-Authors: Sandra Vialebouroncle, Martin Gosau, C. MorsczeckAbstract:Dental follicle cells (DFCs) are dental stem/progenitor cells and the genuine precursors of alveolar osteoblasts and dental cementoblasts. A previous study showed that the transcription factor DLX3 (distal less homeobox 3) supports the Osteogenic Differentiation in DFCs via a positive feedback loop with the bone morghogenetic protein (BMP) 2. Until today, however, the control of this BMP2/DLX3 pathway by additional signaling pathways remains elusive. Previous studies also suggested that the NOTCH signaling pathway plays a role in the Osteogenic Differentiation of DFCs. In this study we showed that DLX3 overexpression and the initiation of the Osteogenic Differentiation by BMP2 or dexamethasone induced the NOTCH signaling pathway in DFCs. However, the induction of NOTCH-signaling impaired not only the Osteogenic Differentiation (ALP activity and mineralized nodules) but also the expression of the transcription factor DLX3 and the activation of the BMP-signaling pathway. So, NOTCH signaling plays a regulatory role for the Osteogenic Differentiation of DFCs. In conclusion, results of our study suggest that the NOTCH-signaling pathway, which is activated during the Osteogenic Differentiation of DFCs, regulates the BMP2/DLX3 directed Differentiation of DFCs via a negative feed-back loop.
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the transcription factor dlx3 regulates the Osteogenic Differentiation of human dental follicle precursor cells
Stem Cells and Development, 2012Co-Authors: Sandra Vialebouroncle, Gottfried Schmalz, Torsten Eugen Reichert, Gero Brockhoff, Oliver Felthaus, C. MorsczeckAbstract:The transcription factor DLX3 plays a decisive role in bone development of vertebrates. In neural-crest derived stem cells from the dental follicle (DFCs), DLX3 is differentially expressed during Osteogenic Differentiation, while other Osteogenic transcription factors such as DLX5 or RUNX2 are not highly induced. DLX3 has therefore a decisive role in the Differentiation of DFCs, but its actual biological effects and regulation are unknown. This study investigated the DLX3-regulated processes in DFCs. After DLX3 overexpression, DFCs acquired a spindle-like cell shape with reorganized actin filaments. Here, marker genes for cell morphology, proliferation, apoptosis, and Osteogenic Differentiation were significantly regulated as shown in a microarray analysis. Further experiments showed that DFCs viability is directly influenced by the expression of DLX3, for example, the amount of apoptotic cells was increased after DLX3 silencing. This transcription factor stimulates the Osteogenic Differentiation of DFCs ...
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soft matrix supports Osteogenic Differentiation of human dental follicle cells
Biochemical and Biophysical Research Communications, 2011Co-Authors: Sandra Vialebouroncle, Gottfried Schmalz, Torsten Eugen Reichert, Florian Völlner, Christoph Mohl, Kevin Kupper, Gero Brockhoff, C. MorsczeckAbstract:The Differentiation of stem cells can be directed by the grade of stiffness of the developed tissue cells. For example a rigid extracellular matrix supports the Osteogenic Differentiation in bone marrow derived mesenchymal stem cells (MSCs). However, less is known about the relation of extracellular matrix stiffness and cell Differentiation of ectomesenchymal dental precursor cells. Our study examined for the first time the influence of the surface stiffness on the proliferation and Osteogenic Differentiation of human dental follicle cells (DFCs). Cell proliferation of DFCs was only slightly decreased on cell culture surfaces with a bone-like stiffness. The Osteogenic Differentiation in DFCs could only be initiated with a dexamethasone based Differentiation medium after using varying stiffness. Here, the softest surface improved the induction of Osteogenic Differentiation in comparison to that with the highest stiffness. In conclusion, different to bone marrow derived MSCs, soft ECMs have a superior capacity to support the Osteogenic Differentiation of DFCs.
Hui Zeng - One of the best experts on this subject based on the ideXlab platform.
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berberine promotes bone marrow derived mesenchymal stem cells Osteogenic Differentiation via canonical wnt β catenin signaling pathway
Toxicology Letters, 2016Co-Authors: Ke Tao, Deming Xiao, Jian Weng, Ao Xiong, Bin Kang, Hui ZengAbstract:Berberine (BBR) has recently been reported to be extensively used for musculoskeletal disorders such as osteoporosis through enhancing Osteogenic Differentiation, inhibiting osteoclastogenesis and bone resorption and repressing adipogenesis. Although canonical Wnt signaling plays a crucial role in suppressing bone marrow-derived mesenchymal stem cells (MSCs) commitment to the chondrogenic and adipogenic lineage and enhancing Osteogenic Differentiation, no previous reports have shown an association between BBR-induced osteogenesis and Wnt/β-catenin signaling pathway. In this study, we aimed to investigate the stimulatory effect and the mechanism of BBR on Osteogenic Differentiation of human bone marrow-derived MSCs. MSCs were isolated from bone marrow specimens and treated with different concentration of BBR. Cell viability was measured by the WST-8 assay. Effects of BBR on Osteogenic Differentiation of MSCs were assessed by von Kossa staining, ALP staining and ALP activity. Osteogenic specific genes, chondrogenic and adipogenic related marker genes were determined by quantitative real-time polymerase chain reaction analysis. Western blot and Immunofluorescence staining were performed to analyze OCN and OPN, and β-catenin expression in the presence or absence of BBR combined with DKK-1 or β-catenin siRNA transfection. Increasing concentration of BBR (3, 10 and 30 μM) promoted Osteogenic Differentiation and Osteogenic genes expression after incubation for various days compared with DMSO group, whereas expression levels of chondrogenic and adipogenic related marker genes were dramatically suppressed. After treated with 10μM BBR for 7 days, β-catenin, OPN and OCN expression were significantly induced, which could be effectively suppressed by the addition of DKK-1 or β-catenin siRNA β-catenin. Interestingly, the expression level of Runx2 gene was also decreased by inhibiting the transduction of Wnt/β-catenin signaling. These findings suggest that BBR can stimulate Osteogenic Differentiation of MSCs not only by enhancing Runx2 expression but also by activating canonical Wnt/β-catenin signaling pathway, and canonical Wnt/β-catenin signaling pathway is in part responsible for BBR-induced Osteogenic Differentiation of MSCs in vitro. BBR is a potential pharmaceutical medicine by enhancing Osteogenic Differentiation for bone disorders, such as osteoporosis.
Zhijun Pan - One of the best experts on this subject based on the ideXlab platform.
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igfbp7 regulates the Osteogenic Differentiation of bone marrow derived mesenchymal stem cells via wnt β catenin signaling pathway
The FASEB Journal, 2017Co-Authors: Wei Zhang, Erman Chen, Mo Chen, Qianhai Ding, Deting Xue, Xiang Gao, Zhijun PanAbstract:Insulin-like growth factor-binding protein 7 (IGFBP7), a low-affinity IGF binder, may play an important role in bone metabolism. However, its function in Osteogenic Differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we investigated its effects on Osteogenic Differentiation. Overexpression of IGFBP7 enhanced the expression of osteo-specific genes and proteins, and IGFBP7 knockdown decreased osteogenesis-specific markers. More mineral deposits and higher alkaline phosphatase activity were observed after the up-regulation of IGFBP7. Moreover, β-catenin levels were up-regulated by the overexpression of IGFBP7 or the addition of extracellular IGFBP7 protein and were reduced by the depletion of IGFBP7. The increase in Osteogenic Differentiation due to the overexpression of IGFBP7 was partially decreased by specific Wnt/β-catenin signaling inhibitors. Using a rat tibial osteotomy model, a sheet of IGFBP7-overexpressing BMSCs improved bone healing, as demonstrated by imaging, biomechanical, and histologic analyses. Taken together, these findings indicate that IGFBP7 regulates the Osteogenic Differentiation of BMSCs partly via the Wnt/β-catenin signaling pathway.-Zhang, W., Chen, E., Chen, M., Ye, C., Qi, Y., Ding, Q., Li, H., Xue, D., Gao, X., Pan, Z. IGFBP7 regulates the Osteogenic Differentiation of bone marrow-derived mesenchymal stem cells via Wnt/β-catenin signaling pathway.
