Undifferentiated human mesenchymal stem cells (hMSCs) are highly sensitive to mechanical strain: transcriptionally controlled early osteo-chondrogenic response in vitro

Friedl, Gerald; Schmidt, Helena; Rehak, I.; Kostner, Gerhard M.; Schauenstein, Konrad; Windhager, Reinhard

doi:10.1016/j.joca.2007.04.002

Cited by 109 publications

(90 citation statements)

References 50 publications

(40 reference statements)

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“…Some study results have shown that mechanical stimulation can promote osteogenic differentiation of MSCs [Sumanasinghe et al, 2006;Friedl et al, 2007;Hanson et al, 2009]; however, the results of our study showed that the increased osteogenic effect on hASCs under combined stimulation decreased after the 5th day. We do not fully understand the reason why this phenomenon occurred in these cells after long-term mechanical stimulation.…”

Section: Discussioncontrasting

confidence: 88%

The Osteogenic Response of Undifferentiated Human Adipose-Derived Stem Cells under Mechanical Stimulation

Zheng²,

Wang

et al. 2012

Cells Tissues Organs

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The purpose of this study was to investigate the osteogenic response of human adipose-derived stem cells (hASCs) under mechanical and/or chemical stimulation. hASCs were divided into three groups. In group A, the cells were cultured without any stimulation, in group B, the cells were induced with chemical stimulation, and in group C, the cells were induced with a combination of chemical stimulation and stretch loading. Stretch loading and chemical stimulation were applied using a four-point bending apparatus (0.5 Hz, 2,000 µε, 2 h/day) and osteogenic differentiation medium, respectively. At the 1st, 2nd, 3rd, 5th and 7th day following initiation of stretch loading, we detected alkaline phosphatase activity, mRNA expression (RUNX2, ALPL, osteonectin, osteopontin and type I collagen) and protein expression (RUNX2 and osteopontin) by colorimetric assay, real-time PCR and Western blot methods, respectively. Alkaline phosphatase activity, mRNA expression and protein expression all increased in groups B and C along with the culture time, but were observed to be downregulated by the 7th day in group C (p < 0.05). Compared to group A, most of the above markers were significantly higher in groups B and C (p < 0.05). All of the above markers in group C were higher than those in group B before the 5th day (p < 0.05), except at the 1st day. These results indicated that stretch loading promoted osteogenic differentiation of hASCs and that the combination of mechanical and chemical stimulation could enhance the osteogenic capability up to the 5th day relative to chemical stimulation alone.

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Section: Discussioncontrasting

confidence: 88%

The Osteogenic Response of Undifferentiated Human Adipose-Derived Stem Cells under Mechanical Stimulation

Zheng²,

Wang

et al. 2012

Cells Tissues Organs

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“…In fact, although a dilatational component can always be identified for any given loading regime, many tissues of interest experience in vivo stress states that depart very substantially from purely hydrostatic pressure [Potier et al, 2010]. To drive osteogenesis, there are still numerous other forms of mechanical stimulation including but not limited to: substrate strain in uniaxial [Diederichs and van Freiberger, 2009], biaxial or equiaxial directions [Qi et al, 2008;Friedl et al, 2007] and shear stress [Stiehler et al, 2009;Kreke et al, 2008], each having been proven to contribute to new bone formation and maturation. Further research is required to know if estrogen has a synergistic effect with all types of mechanical stimulation that BMSCs encounter, or if its effects are limited to only a few forms of mechanical strain.…”

Section: Discussionmentioning

confidence: 99%

Estrogen and Its Receptor Enhance Mechanobiological Effects in Compressed Bone Mesenchymal Stem Cells

Zhang

Chen²,

Wang³

et al. 2011

Cells Tissues Organs

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Mechanical stimulation and estrogen have been proven to be two important factors in promoting mesenchymal stem cell activity, which is closely associated with bone formation, mass maintenance and remodeling. However, the superposition effects of mechanical stimulation and estrogen on stem cells remain unknown. It is also unclear if the estrogen receptor (ER) plays only a key role in estrogen signaling or if it is also involved in the mechanotransduction of stem cells. To investigate the role of estrogen and its receptors in the mechanobiological effects in bone mesenchymal stem cells (BMSCs), isolated mesenchymal stem cells from bone marrow were exposed to mechanical pressure under additional estrogen treatment or ER blockade. Cell proliferation was examined using an MTT assay and alkaline phosphatase (ALP) activity was determined by a modified enzyme kinetic method. Alignment of the cytoskeleton was observed by Coomassie brilliant blue staining and F-actin fluorescent staining. Cellular ultrastructure was observed under transmission electron microscope. Expression of ERα was investigated using Western blot analysis. Results indicated that mechanical pressure promoted cell proliferation, ALP activity, ERα expression and F-actin stress fiber formation. Overall, this effect was enhanced by the addition of estrogen and inhibited by ER blockade. We concluded that pressure stimulated proliferation and differentiation capability via F-actin transduction in BMSCs. The effects were enhanced by the addition of estrogen, and the ER plays an important role in regulating mechanobiological effects and the mechanotransduction processes of BMSCs.

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“…FosB is implicated in playing a profibrotic role in that it can induce tenascin-C and CTGF in smooth muscle cells after loading (35). Fos proteins (both c-Fos and FosB), together with Jun, form a complex, AP-1, which is important in cell proliferation and differentiation (8,25), and both genes are important during differentiation of cells with mesenchymal origin such as osteoblasts and chondrocytes (14,15,17,19,36), and might therefore also be involved in tenocyte differentiation. The AP-1 complex also has a binding site in the promoter for collagen type 1 (15), which is the predominating collagen in normal tendons.…”

Section: Fosb and C-fos: Transcription Factors Involved In Proliferatmentioning

confidence: 99%

Primary gene response to mechanical loading in healing rat Achilles tendons

Eliasson

Andersson

Hammerman

et al. 2013

Journal of Applied Physiology

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Eliasson P, Andersson T, Hammerman M, Aspenberg P. Primary gene response to mechanical loading in healing rat Achilles tendons. J Appl Physiol 114: 1519 -1526, 2013. First published March 21, 2013 doi:10.1152/japplphysiol.01500.2012.-Loading can stimulate tendon healing. In healing rat Achilles tendons, we have found more than 150 genes upregulated or downregulated 3 h after one loading episode. We hypothesized that these changes were preceded by a smaller number of regulatory genes and thus performed a microarray 15 min after a short loading episode, to capture the primary response to loading. We transected the Achilles tendon of 54 rats and allowed them to heal. The hind limbs were unloaded by tail-suspension during the entire experiment, except during the loading episode. The healing tendon tissue was analyzed by mechanical testing, microarray, and quantitative real-time polymerase chain reaction (qRT-PCR). Mechanical testing showed that 5 min of loading each day for 4 days created stronger tissue. The microarray analysis after one loading episode identified 15 regulated genes. Ten genes were analyzed in a repeat experiment with new rats using qRT-PCR. This confirmed the increased expression of four genes: early growth response 2 (Egr2), c-Fos, FosB, and regulation of G protein signaling 1 (Rgs1). The other genes were unaltered. We also analyzed the expression of early growth response 1 (Egr1), which is often coregulated with c-Fos or Egr2, and found that this was also increased after loading. Egr1, Egr2, c-Fos, and FosB are transcription factors that can be triggered by numerous stimuli. However, Egr1 and Egr2 are necessary for normal tendon development, and can induce ectopic expression of tendon markers. The five regulated genes appear to constitute a general activation machinery. The further development of gene regulation might depend on the tissue context. tail-suspension; treadmill walking; tendon repair; early growth response; microarray TENDONS ADAPT TO CHANGES IN mechanical loading (5,6,20), and sufficient mechanical stimulation appears to be required for appropriate healing of ruptured tendons (11,12,34). Yet there is always a risk of re-rupture if too much loading is applied after injury. In rats, short daily episodes of loading of an otherwise unloaded healing Achilles tendon increases the strength of the healing tissue (1, 9, 10). In human patients, early weight bearing after surgical repair of Achilles tendon ruptures has been suggested to improve the clinical outcome (26,43).Mechanical loading stimulates collagen expression during tendon healing (11). At least in rats, it results in an increased cross-sectional area of the callus tissue, leading to an increase in strength (11). The mechanisms behind the effect of mechanical stimulation are not fully understood, and the signaling pathways involved in tendon mechano-transduction in vivo are not well described. We previously studied the changes in gene expression that arise when an unloaded healing tendon is exposed to 30 min of loading (10). We ...

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Undifferentiated human mesenchymal stem cells (hMSCs) are highly sensitive to mechanical strain: transcriptionally controlled early osteo-chondrogenic response in vitro

Abstract: Undifferentiated hMSCs are highly sensitive to mechanical strain with a transcriptionally controlled osteo-chondrogenic differentiation response in vitro.

Cited by 109 publications

References 50 publications

The Osteogenic Response of Undifferentiated Human Adipose-Derived Stem Cells under Mechanical Stimulation

The Osteogenic Response of Undifferentiated Human Adipose-Derived Stem Cells under Mechanical Stimulation

Estrogen and Its Receptor Enhance Mechanobiological Effects in Compressed Bone Mesenchymal Stem Cells

Primary gene response to mechanical loading in healing rat Achilles tendons

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