Mechanical stretch inhibits mesenchymal stem cell adipogenic differentiation through TGFβ1/Smad2 signaling

Li, Runguang; Liang, Liang; Dou, Yong-gang; Huang, Zhichao; Mo, Huiting; Wang, Yaning; Yu, Bin

doi:10.1016/j.jbiomech.2015.08.013

Cited by 33 publications

(23 citation statements)

References 46 publications

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“…For example, both BMP and TGF-β signaling increase baseline cellular contractility (Bhadriraju et al, 2007). Our data show that TGF-β expression is highly upregulated with dynamic stretch at early time points and while TGF-β in the media did not reach detectable levels, we did observe increased Smad3 signaling in response to stretch (Figure 6—figure supplement 1e, [Furumatsu et al, 2013; Li et al, 2015]). Thus, elements of the TGF-signaling pathway may be mechano-responsive, in a ligand or ligand-less fashion (Heo et al, 2016).…”

Section: Discussionmentioning

confidence: 69%

Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity

Heo

Driscoll

Thorpe

et al. 2016

eLife

155

124

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Mesenchymal stem cell (MSC) differentiation is mediated by soluble and physical cues. In this study, we investigated differentiation-induced transformations in MSC cellular and nuclear biophysical properties and queried their role in mechanosensation. Our data show that nuclei in differentiated bovine and human MSCs stiffen and become resistant to deformation. This attenuated nuclear deformation was governed by restructuring of Lamin A/C and increased heterochromatin content. This change in nuclear stiffness sensitized MSCs to mechanical-loading-induced calcium signaling and differentiated marker expression. This sensitization was reversed when the ‘stiff’ differentiated nucleus was softened and was enhanced when the ‘soft’ undifferentiated nucleus was stiffened through pharmacologic treatment. Interestingly, dynamic loading of undifferentiated MSCs, in the absence of soluble differentiation factors, stiffened and condensed the nucleus, and increased mechanosensitivity more rapidly than soluble factors. These data suggest that the nucleus acts as a mechanostat to modulate cellular mechanosensation during differentiation.DOI: http://dx.doi.org/10.7554/eLife.18207.001

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Section: Discussionmentioning

confidence: 69%

Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity

Heo

Driscoll

Thorpe

et al. 2016

eLife

155

124

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“…When the cells reached 80%-90% confluence, they were washed with PBS, detached by 0.25% trypsin, and subcultured in new 25 cm 2 flasks at 1 × 10 4 cells/cm 2 . Cells were collected at the second or third generation and sent for flow cytometry analysis (BD, Franklin Lakes, NJ, USA) of CD29, CD34, CD44, and CD45 expression for confirmation of BMSC phenotype [13,14].…”

Section: Isolation and Culture Of Rat Bmscsmentioning

confidence: 99%

“…Previous studies have shown that lack of exercise and the associated reduction in stem cell mechanical stimulation decreases osteogenic differentiation and increases the risk of osteoporosis [11,12]. Indeed, our previous studies have demonstrated that mechanical stress can promote osteogenic differentiation and inhibit adipogenic differentiation of BMSCs [13,14]. Further understanding of how mechanical stimuli, especially mechanical stress, affect skeletal tissue differentiation will provide insight into bone repair processes that may be exploited for novel therapeutic strategies.…”

mentioning

confidence: 96%

Mechanical stimulation regulates differentiation of bone marrow stem cells by modulating miR-140-5p via TGFβ1/Smad2 signaling pathway

Qian¹,

Zhu²,

Ye³

et al. 2020

Preprint

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Background: Osteoporosis is a common progressive bone disease that drastically impairs patient health, independent mobility, and quality of life, and there is an urgent need for improved preventive and therapeutic strategies. A shift in bone marrow mesenchymal stem cell (BMSC) differentiation from osteogenic to adipogenic may contribute to disease pathogenesis. Mechanical stress on BMSCs is reported to promote osteogenesis, so we examined the effects of mechanical stimulation on BMSC differentiation and associated signaling pathways.Methods: A sinusoidal tensile stress loading device was developed and examined effects of mechanical (stretch) stimulation on cultured BMSC (isolated from Sprague-Dawley rats) phenotype under osteogenic and adipogenic culture conditions. Osteogenic differentiation of BMSCs was assessed by alkaline phosphatase (ALP) staining and expression of Runx2 and BMP2, while adipogenic differentiation was evaluated by oil red O staining and expression of PPARγ and C/EBPα.Results: It demonstrated that appropriate mechanical stimulation could promote osteogenic differentiation of BMSCs and inhibit differentiation into adipocytes. The mechanic stimuli could inhibit the expression of miR-140-5P in BMSCs, and the overexpression of miR-140-5P inhibited the osteogenic differentiation, whereas the inhibition of miR-140-5P promoted the osteogenic differentiation. Further, both mechanical stimulation and miR-140-5p knockdown promoted TGFβ1/Smad2 signaling, while miR-140-5p overexpression downregulated TGFβ1/ Smad2 signaling.Conclusions: Appropriate mechanical stimulation promoted osteogenic differentiation and inhibited the adipogenic differentiation of BMSCs by lowering miR-140-5p expression, which in turn upregulates the TGFβ1/Smad2 signaling pathway. Our results provide a foundation for the development of effective strategies to promote bone remodeling, thereby lowering the burden of osteoporosis.

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“…Here, the authors found that by pretreating MSCs with TGFβ1/Smad2 pathway antagonists suppressed this increase in Smad2 phosphorylation, whereas pretreatment with TGFβ1/Smad2 signalling agonists facilitated the inhibitory effect of stretch on the adipogenic differentiation markers, suggesting that the anti-adipogenic effects of stretch are mediated in some way by the activation of the TGFβ1/Smad2 signalling pathway [42]. …”

Section: The Effect Of Tensile Strain On Progenitor Cell Proliferatiomentioning

confidence: 99%

Mechanical stretch and chronotherapeutic techniques for progenitor cell transplantation and biomaterials

Rogers¹,

Pekovic-Vaughan²,

Hunt³

2018

BioMedicine

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In the body, mesenchymal progenitor cells are subjected to a substantial amount external force from different mechanical stresses, each potentially influences their behaviour and maintenance differentially. Tensile stress, or compression loading are just two of these forces, and here we examine the role of cyclical or dynamic mechanical loading on progenitor cell proliferation and differentiation, as well as on other cellular processes including cell morphology, apoptosis and matrix mineralisation. Moreover, we also examine how mechanical stretch can be used to optimise and ready biomaterials before their implantation, and examine the role of the circadian rhythm, the body’s innate time keeping system, on biomaterial delivery and acceptance. Finally, we also investigate the effect of mechanical stretch on the circadian rhythm of progenitor cells, as research suggests that mechanical stimulation may be sufficient in itself to synchronise the circadian rhythm of human adult progenitor cells alone, and has also been linked to progenitor cell function. If proven correct, this could offer a novel, non-intrusive method by which human adult progenitor cells may be activated or preconditioned, being readied for differentiation, so that they may be more successfully integrated within a host body, thereby improving tissue engineering techniques and the efficacy of cellular therapies.

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Mechanical stretch inhibits mesenchymal stem cell adipogenic differentiation through TGFβ1/Smad2 signaling

Cited by 33 publications

References 46 publications

Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity

Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity

Mechanical stimulation regulates differentiation of bone marrow stem cells by modulating miR-140-5p via TGFβ1/Smad2 signaling pathway

Mechanical stretch and chronotherapeutic techniques for progenitor cell transplantation and biomaterials

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