Effects of dynamic tensile loading on TGF and BMP signaling pathways in mesenchymal stem cells on aligned nanofibrous scaffolds

2012 ◽  
Author(s):  
S. J. Heo ◽  
T. P. Driscoll ◽  
R. L. Mauck
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Tensile Loading ◽  
Bmp Signaling ◽  
Nanofibrous Scaffolds ◽  
Dynamic Tensile Loading

Spontaneous osteogenic differentiation of mesenchymal stem cells on electrospun nanofibrous scaffolds

RSC Advances ◽  
2016 ◽  
Vol 6 (26) ◽  
pp. 22144-22152 ◽  
Author(s):  
Ning Zhang ◽  
Qian-Ru Xiao ◽  
Xin-Yao Man ◽  
Hai-Xia Liu ◽  
Lan-Xin Lü ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Signaling Pathways ◽  
Nanofibrous Scaffolds

Hydroxyapatite-containing PHBV nanofibrous scaffolds accelerate osteogenic differentiation of MSCs by activating the related signaling pathways.

Salidroside induces neuronal differentiation of mouse mesenchymal stem cells through Notch and BMP signaling pathways

2014 ◽  
Vol 71 ◽  
pp. 60-67 ◽  
Author(s):  
Hong-Bin Zhao ◽  
She-Ning Qi ◽  
Ju-Zi Dong ◽  
Xiao-Qin Ha ◽  
Xiao-Yun Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Neuronal Differentiation ◽  
Bmp Signaling

Dynamic Tensile Loading Activates TGF and BMP Signaling in Mesenchymal Stem Cells on Aligned Nanofibrous Scaffolds

2012 ◽  
Author(s):  
Su-Jin Heo ◽  
Tristan P. Driscoll ◽  
Robert L. Mauck
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transforming Growth Factor Beta ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Bmp Signaling ◽  
Nanofibrous Scaffolds ◽  
Smad Phosphorylation

Mesenchymal stem cells (MSCs) are a promising cell source for tissue engineering applications, given their ease of isolation and multi-potential differentiation capacity [1]. External mechanical cues directly influence MSC lineage commitment [2]. However, it is not yet clear how these physical cues are transduced to the cell nucleus, an understanding of which may prove essential for orthopaedic tissue engineering. Transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP), members of the TGF beta superfamily, regulate cellular processes including growth and differentiation [3, 4]. TGF and/or BMP ligand binding initiate SMAD phosphorylation, translocation to the nucleus, and transcriptional activation of target genes [4]. Additionally, both ligands can influence the organization of chromatin and the Lamin A/C (LMAC) nucleoskeletal network [5]. For example, we have recently shown that TGF-β3 leads to corticalized LMAC, marked increases in heterochromatin (HTC), and increased nuclear stiffness [6]. Interestingly, dynamic tensile stretch of MSCs on aligned nanofibrous scaffolds, in the absence of these differentiation factors, resulted in many of these same nuclear transformations [6, 7]. The objective of this study was to identify how dynamic tensile stress is transduced in MSCs on aligned nanofibrous scaffolds, and further, to ascertain whether these mechanoregulatory changes are coordinated through TGFβ/BMP signaling pathways.

scholarly journals Akt signaling is activated by TGFβ2 and impacts tenogenic induction of mesenchymal stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sophia K. Theodossiou ◽  
Jett B. Murray ◽  
LeeAnn A. Hold ◽  
Jeff M. Courtright ◽  
Anne M. Carper ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Akt Signaling ◽  
Cell Alignment ◽  
Limited Information ◽  
Akt Inhibitor ◽  
Tenogenic Differentiation

Abstract Background Tissue engineered and regenerative approaches for treating tendon injuries are challenged by the limited information on the cellular signaling pathways driving tenogenic differentiation of stem cells. Members of the transforming growth factor (TGF) β family, particularly TGFβ2, play a role in tenogenesis, which may proceed via Smad-mediated signaling. However, recent evidence suggests some aspects of tenogenesis may be independent of Smad signaling, and other pathways potentially involved in tenogenesis are understudied. Here, we examined the role of Akt/mTORC1/P70S6K signaling in early TGFβ2-induced tenogenesis of mesenchymal stem cells (MSCs) and evaluated TGFβ2-induced tenogenic differentiation when Smad3 is inhibited. Methods Mouse MSCs were treated with TGFβ2 to induce tenogenesis, and Akt or Smad3 signaling was chemically inhibited using the Akt inhibitor, MK-2206, or the Smad3 inhibitor, SIS3. Effects of TGFβ2 alone and in combination with these inhibitors on the activation of Akt signaling and its downstream targets mTOR and P70S6K were quantified using western blot analysis, and cell morphology was assessed using confocal microscopy. Levels of the tendon marker protein, tenomodulin, were also assessed. Results TGFβ2 alone activated Akt signaling during early tenogenic induction. Chemically inhibiting Akt prevented increases in tenomodulin and attenuated tenogenic morphology of the MSCs in response to TGFβ2. Chemically inhibiting Smad3 did not prevent tenogenesis, but appeared to accelerate it. MSCs treated with both TGFβ2 and SIS3 produced significantly higher levels of tenomodulin at 7 days and morphology appeared tenogenic, with localized cell alignment and elongation. Finally, inhibiting Smad3 did not appear to impact Akt signaling, suggesting that Akt may allow TGFβ2-induced tenogenesis to proceed during disruption of Smad3 signaling. Conclusions These findings show that Akt signaling plays a role in TGFβ2-induced tenogenesis and that tenogenesis of MSCs can be initiated by TGFβ2 during disruption of Smad3 signaling. These findings provide new insights into the signaling pathways that regulate tenogenic induction in stem cells.

scholarly journals Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

2015 ◽  
Vol 35 (10) ◽  
pp. 1700-1711 ◽  
Author(s):  
Fenfang Chen ◽  
Xia Lin ◽  
Pinglong Xu ◽  
Zhengmao Zhang ◽  
Yanzhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Nuclear Export ◽  
Stem Cell Differentiation ◽  
Bmp Signaling ◽  
Dependent Manner ◽  
Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

scholarly journals Mesenchymal stem cells regulate maintenance of neural stem cells through VEGFR2 and Notch signaling pathways

Cell Research ◽  
2008 ◽  
Vol 18 (S1) ◽  
pp. S59-S59
Author(s):  
Zhifeng Deng ◽  
Zhumin Liu ◽  
Wei Tu ◽  
Yang Wang ◽  
Yuanlei Lou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neural Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathways

scholarly journals Adenosine Triphosphate Prevents Serum Deprivation-Induced Apoptosis in Human Mesenchymal Stem Cells via Activation of the MAPK Signaling Pathways

Stem Cells ◽  
2014 ◽  
Vol 33 (1) ◽  
pp. 211-218 ◽  
Author(s):  
Jessica L. Berlier ◽  
Sabrina Rigutto ◽  
Antoine Dalla Valle ◽  
Jessica Lechanteur ◽  
Muhammad S. Soyfoo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Adenosine Triphosphate ◽  
Human Mesenchymal Stem Cells ◽  
Mapk Signaling ◽  
Serum Deprivation ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways

scholarly journals SIRT6 promotes osteogenic differentiation of mesenchymal stem cells through BMP signaling

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Ping Zhang ◽  
Yunsong Liu ◽  
Yuejun Wang ◽  
Min Zhang ◽  
Longwei Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bmp Signaling
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