Altered osteogenic commitment of human mesenchymal stem cells by ERM protein-dependent modulation of cellular biomechanics

Titushkin, Igor; Cho, Michael

doi:10.1016/j.jbiomech.2011.07.024

Cited by 29 publications

(28 citation statements)

References 33 publications

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“…As RhoA is a member of the GTPase family that has been shown to control actin stress fibers and focal adhesions (Titushkin and Cho, 2011;Titushkin et al, 2010aTitushkin et al, , 2010b, its activation may stabilize actins and form stress fibers and subsequently regulate cellular cytoskeleton and morphology. The important role of cytoskeleton has been repeatedly demonstrated, particularly for the load-bearing cell types, such as muscle cells.…”

Section: Discussionmentioning

confidence: 99%

“…Full experimental details have been provided elsewhere (Titushkin and Cho, 2007;Titushkin and Cho, 2011;Titushkin et al, 2013;Sun et al, 2013). Briefly, to obtain a forcedistance curve, an AFM cantilever (0.12 N/m) with a 5-μm radius microindentor descended toward the cell at$ 2 mm/s to minimize hysteresis and until a trigger force of 3 nN was reached.…”

Section: Measurement On Cell Stiffness Using Afmmentioning

confidence: 99%

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Impact of oxidative stress on cellular biomechanics and rho signaling in C2C12 myoblasts

Sun¹,

Wong²,

Mak³

et al. 2014

Journal of Biomechanics

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Section: Discussionmentioning

confidence: 99%

Section: Measurement On Cell Stiffness Using Afmmentioning

confidence: 99%

Impact of oxidative stress on cellular biomechanics and rho signaling in C2C12 myoblasts

Sun¹,

Wong²,

Mak³

et al. 2014

Journal of Biomechanics

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“…They are known to be specifically involved in the osteogenic differentiation of MSCs [25] and are thought to be of particular importance in osteoblast differentiation on collagen-based substrates [26]. FA formation is also known to be affected by changes in substrate stiffness [7].…”

Section: Introductionmentioning

confidence: 99%

Cell morphology and focal adhesion location alters internal cell stress

Mullen

Vaughan

Voisin

et al. 2014

J. R. Soc. Interface.

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Extracellular mechanical cues have been shown to have a profound effect on osteogenic cell behaviour. However, it is not known precisely how these cues alter intracellular mechanics to initiate changes in cell behaviour. In this study, a combination of in vitro culture of MC3T3-E1 cells and finiteelement modelling was used to investigate the effects of passive differences in substrate stiffness on intracellular mechanics. Cells on collagen-based substrates were classified based on the presence of cell processes and the dimensions of various cellular features were quantified. Focal adhesion (FA) density was quantified from immunohistochemical staining, while cell and substrate stiffnesses were measured using a live-cell atomic force microscope. Computational models of cell morphologies were developed using an applied contraction of the cell body to simulate active cell contraction. The results showed that FA density is directly related to cell morphology, while the effect of substrate stiffness on internal cell tension was modulated by both cell morphology and FA density, as investigated by varying the number of adhesion sites present in each morphological model. We propose that the cells desire to achieve a homeostatic stress state may play a role in osteogenic cell differentiation in response to extracellular mechanical cues.

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“…Abbreviations: FAs, Focal Adhesions; G-Actin, Globular Actin; F-Actin, Filamentous Actin; LIMK, (Lin11/Isl1/Mec3) Kinase; P120 or Catenin Delta 1, A prototypic member of Armadillo protein family; ROCK, Rho-associated protein kinase; Src (Sarcoma), A proto-oncogene which encodes non-receptor tyrosine kinases scription factor A (MRTF). This type of protein, which is found in both cytoplasm and nucleus, interacts with G-actins [188][189][190][191][192][193][194] . In the nucleus the inactive form of MRTF is bound to G-actin.…”

Section: Conclusion and Future Challengesmentioning

confidence: 99%

“…Silencing the expression of ERM genes causes disassembly of actin fibers and FAs. These mechanical changes subsequently lead to impaired osteogenic differentiation 191 . It is also assumed that any changes in the distribution of FAs and cytoskeleton remodeling are translocated to the nucleoskeleton via bridging proteins, including SUN and nesprins, and hence to the DNA through matrix attachment regions 192 .…”

Section: Abbreviationsmentioning

confidence: 99%

The effect of nano-scale topography on osteogenic differentiation of mesenchymal stem cells

Faghihi

Eslaminejad²

2014

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Large bone defects resulting from trauma or disease pose a threat to humans. Thus far, tissue engineering as an important clinical approach uses cells, growth factors and scaffolds to regenerate large areas of damaged bone tissue. Since bone is a nanocomposite structure, it is assumed that nanomaterial scaffolds can induce or promote osteogenesis by mimicking the cell niche at nano level. Methods and Results. In this review we highlighted the effect of nano-scale topography on osteogenic differentiation of Mesenchymal Stem Cells (MSCs) as potent cell candidates in bone engineered constructs. The key point in the induction of differentiation by nanomaterials is the discontinuity in their topography. This leads to alteration in protein adsorption and restriction of extracellular matrix deposition by the cells and consequently leads to changes in cell morphology and the frequency of accessible sites for cell adhesion. Here, we have reviewed the literature on the role of different types of nanomateial scaffolds in osteogenic differentiation of these cells. Since little is known about the underlying molecular networks induced by nanomaterials, we also reviewed possible underlying mechanisms of nanotopographical effects on the osteogenic differentiation of MSCs. Conclusions. Nano-scale materials provide a niche which is very similar to native bone in geometry and stiffness. Such nano-scale topographies improve the function of MSC-based engineered constructs in regeneration of bone defects.

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Altered osteogenic commitment of human mesenchymal stem cells by ERM protein-dependent modulation of cellular biomechanics

Cited by 29 publications

References 33 publications

Impact of oxidative stress on cellular biomechanics and rho signaling in C2C12 myoblasts

Impact of oxidative stress on cellular biomechanics and rho signaling in C2C12 myoblasts

Cell morphology and focal adhesion location alters internal cell stress

The effect of nano-scale topography on osteogenic differentiation of mesenchymal stem cells

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