Mechanical stimulation induced osteogenic differentiation of BMSCs through TWIST/E2A/p21 axis

Guo, Qingyuan; Liu, Ying; Sun, Ruyi; Yang, Fang; Qiao, Pengyan; Zhang, Rong; Ling, Song; Lingling, E; Liu, Hongchen

doi:10.1042/bsr20193876

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…Exogenous mechanical stimuli could induce the physiological responsiveness of various cells and play an important role in regulating the structure and function of cells ( Guo et al, 2020 ; Li et al, 2020 ). Flexcell ® FX- 5000™ Tension System is a computer-regulated bioreactor, which applies cyclic or static strain to cells on flexible-bottomed cultures plates through the use of vacuum pressure ( Wu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Here, our results revealed that mechanical tension significantly promoted osteoblastic differentiation and PC2 was critically required for mechanical tension-induced osteogenesis differentiation of hASCs by activating TAZ. Exogenous mechanical stimuli could induce the physiological responsiveness of various cells and play an important role in regulating the structure and function of cells (Guo et al, 2020;. Flexcell ® FX-5000 ™ Tension System is a computerregulated bioreactor, which applies cyclic or static strain to cells on flexible-bottomed cultures plates through the use of vacuum pressure (Wu et al, 2018).…”

Section: Frontiers In Physiology Frontiersinorgmentioning

confidence: 99%

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Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif

Wang

Lu²,

Cai³

et al. 2022

Front. Physiol.

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Human adipose-derived stem cells (hASCs) have multi-directional differentiation potential including osteogenic differentiation. Mechanical stimulation is thought to be a key regulator of bone remodeling and has been proved to promote osteogenic differentiation of mesenchymal stem cells. However, the mechanism how mechanical tension-induced osteogenesis of hASCs still remains poor understood. Polycystin-2 (PC2), a member of the transient receptor potential polycystic (TRPP) family, is involved in cilia-mediated mechanical transduction. To understand the role of PC2 in osteogenic differentiation under mechanical stimuli in hASCs, PKD2 gene was stably silenced by using lentivirus-mediated shRNA technology. The results showed that mechanical tension sufficiently enhanced osteogenic differentiation but hardly affected proliferation of hASCs. Silencing PKD2 gene caused hASCs to lose the ability of sensing mechanical stimuli and subsequently promoting osteogenesis. PC2 knock-out also reduced the cilia population frequency and cilia length in hASCs. TAZ (transcriptional coactivator with PDZ-binding motif, also known as Wwtr1) could mediate the genes regulation and biological functions of mechanotransduction signal pathway. Here, mechanical tension also enhanced TAZ nuclear translocation of hASCs. PC2 knock-out blocked tension-induced upregulation of nuclear TAZ and suppress tension-induced osteogenesis. TAZ could directly interact with Runx2, and inhibiting TAZ could suppress tension-induced upregulation of Runx2 expression. In summary, our findings demonstrated that PC2 mediate mechanical tension-induced osteogenic differentiation of hASCs by activating TAZ.

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Section: Discussionmentioning

confidence: 99%

Section: Frontiers In Physiology Frontiersinorgmentioning

confidence: 99%

Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif

Wang

Lu²,

Cai³

et al. 2022

Front. Physiol.

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“…Several studies have demonstrated that mechanical forces induce the differentiation and maturation of stem cells toward bone 4,24,25 and cartilage cells 11,[26][27][28] . Laminar shear stress mediates early lineage specification of singlecell monolayer-cultured mouse ES cells 6 .…”

Section: Discussionmentioning

confidence: 99%

Application of shear stress for enhanced osteogenic differentiation of mouse induced pluripotent stem cells

Limraksasin

Nattasit

Manokawinchoke

et al. 2022

Sci Rep

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The self-organizing potential of induced pluripotent stem cells (iPSCs) represents a promising tool for bone tissue engineering. Shear stress promotes the osteogenic differentiation of mesenchymal stem cells, leading us to hypothesize that specific shear stress could enhance the osteogenic differentiation of iPSCs. For osteogenesis, embryoid bodies were formed for two days and then maintained in medium supplemented with retinoic acid for three days, followed by adherent culture in osteogenic induction medium for one day. The cells were then subjected to shear loading (0.15, 0.5, or 1.5 Pa) for two days. Among different magnitudes tested, 0.5 Pa induced the highest levels of osteogenic gene expression and greatest mineral deposition, corresponding to upregulated connexin 43 (Cx43) and phosphorylated Erk1/2 expression. Erk1/2 inhibition during shear loading resulted in decreased osteogenic gene expression and the suppression of mineral deposition. These results suggest that shear stress (0.5 Pa) enhances the osteogenic differentiation of iPSCs, partly through Cx43 and Erk1/2 signaling. Our findings shed light on the application of shear-stress technology to improve iPSC-based tissue-engineered bone for regenerative bone therapy.

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“…p21 has different regulatory effects on RUNX2 and BMP2, maintaining a relative balance between osteogenic factors. Meanwhile, p21 acts as a downstream gene of TWIST and E2A, regulating TWIST expression positively and E2A expression negatively [ 124 ] (Fig. 4 ).…”

Section: Mechanisms For Perceiving the Mechanical Environmentmentioning

confidence: 99%

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

Zhang

Wang

2022

Stem Cell Res Ther

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Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostatic pressure, tension, and microgravity. We then detail the currently known signalling pathways that stem cells use to perceive the mechanical environment, including those involving nuclear factor-kB, the nicotinic acetylcholine receptor, the piezoelectric mechanosensitive ion channel, and hypoxia-inducible factor 1α. Using this information in clinical settings to treat diseases is the goal of this research, and we describe the progress that has been made. In this review, we examined the effects of mechanical factors in the stem cell growth microenvironment on stem cell differentiation, how mechanical signals are transmitted to and function within the cell, and the influence of mechanical factors on the use of stem cells in clinical applications.

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Mechanical stimulation induced osteogenic differentiation of BMSCs through TWIST/E2A/p21 axis

Cited by 7 publications

References 43 publications

Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif

Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif

Application of shear stress for enhanced osteogenic differentiation of mouse induced pluripotent stem cells

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

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