Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness

Pongkitwitoon, Suphannee; Uzer, Gunes; Rubin, Janet; Judex, Stefan

doi:10.1038/srep34791

Cited by 42 publications

(50 citation statements)

References 59 publications

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“…The HF vibration has been especially popular in inducing the osteogenic responses of stem cells [9][10][11]35] and in differentiation of the vocal fold tissues [16]. However, these stimulation effects have been studied with methods, which require special treatments of the samples and don't allow live cell imaging.…”

Section: Applicability For Mechanobiology Research With Live Cellsmentioning

confidence: 99%

Mechanical impact stimulation platform tailored for high-resolution light microscopy

2019

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High frequency (HF) mechanical vibration has been used in vitro to study the cellular response to mechanical stimulation and induce stem cell differentiation. However, detailed understanding of the effect of the mechanical cues on cellular physiology is lacking. To meet this limitation, we have designed a system, which enables monitoring of living cells by high-resolution light microscopy during mechanical stimulation by HF vibration or mechanical impacts. The system consists of a commercial speaker, and a 3D printed sample vehicle and frame. The speaker moves the sample in the horizontal plane, allowing simultaneous microscopy. The HF vibration (30-200 Hz) performances of two vehicles made of polymer and aluminum were characterized with accelerometer. The mechanical impacts were characterized by measuring the acceleration of the aluminum vehicle and by time lapse imaging. The lighter polymer vehicle produced higher HF vibration magnitudes at 30-50 Hz frequencies than the aluminum vehicle. However, the aluminum vehicle performed better at higher frequencies (60-70 Hz, 90-100 Hz, 150 Hz). Compatibility of the system in live cell experiments was investigated with epithelial cells (MDCKII, expressing Emerald-Occludin) and HF (0.56 G peak, 30 Hz and 60 Hz) vibration. Our findings indicated that our system is compatible with highresolution live cell microscopy. Furthermore, the epithelial cells were remarkable stable under mechanical vibration stimulation. To conclude, we have designed an inexpensive tool for the studies of cellular biophysics, which combines versatile in vivo like mechanical stimuli with live cell imaging, showing a great potential for several cellular applications.

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Section: Applicability For Mechanobiology Research With Live Cellsmentioning

confidence: 99%

Mechanical impact stimulation platform tailored for high-resolution light microscopy

2019

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“…Flow shear stress (FSS) can also induce a variety of responses such as recruitment, proliferation, and osteogenic differentiation of BMSCs, thus promoting bone formation . Low intensity vibrations signal enhanced BMSC proliferation, osteogenic differentiation, and up‐regulation of genes associated with cytoskeletal structure . These responses to mechanical stimuli are reduced with aging, and the age‐related loss of osteogenic potential in BMSCs can be attributed in part to the impairment in IGF‐1 signaling in BMSCs.…”

Section: Role Of Igf‐1 In the Mesenchymal Stem Cell Response To Mechamentioning

confidence: 99%

“…23 Low intensity vibrations signal enhanced BMSC proliferation, osteogenic differentiation, and up-regulation of genes associated with cytoskeletal structure. 24 These responses to mechanical stimuli are reduced with aging, and the age-related loss of osteogenic potential in BMSCs can be attributed in part to the impairment in IGF-1 signaling in BMSCs. On the other hand IGF-1 overexpression in aging BMSCs facilitates the formation of cell clusters in scaffolds, increases cell survival inside the cell clusters, induces the expression of osteoblast markers, and enhances the biomineralization of cell clusters.…”

mentioning

confidence: 99%

IGF‐1 signaling mediated cell‐specific skeletal mechano‐transduction

Tian

Wang

Bikle

2017

Journal Orthopaedic Research

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Mechanical loading preserves bone mass and stimulates bone formation, whereas skeletal unloading leads to bone loss. In addition to osteocytes, which are considered the primary sensor of mechanical load, osteoblasts, and bone specific mesenchymal stem cells also are involved. The skeletal response to mechanical signals is a complex process regulated by multiple signaling pathways including that of insulin-like growth factor-1 (IGF-1). Conditional osteocyte deletion of IGF-1 ablates the osteogenic response to mechanical loading. Similarly, osteocyte IGF-1 receptor (IGF-1R) expression is necessary for reloading-induced periosteal bone formation. Transgenic overexpression of IGF-1 in osteoblasts results in enhanced responsiveness to in vivo mechanical loading in mice, a response which is eliminated by osteoblastic conditional disruption of IGF-1 in vivo. Bone marrow derived stem cells (BMSC) from unloaded bone fail to respond to IGF-1 in vitro. IGF-1R is required for the transduction of a mechanical stimulus to downstream effectors, transduction which is lost when the IGF-1R is deleted. Although the molecular mechanisms are not yet fully elucidated, the IGF signaling pathway and its interactions with potentially interlinked signaling cascades involving integrins, the estrogen receptor, and wnt/β-catenin play an important role in regulating adaptive response of cancer bone cells to mechanical stimuli. In this review, we discuss recent advances investigating how IGF-1 and other interlinked molecules and signaling pathways regulate skeletal mechano-transduction involving different bone cells, providing an overview of the IGF-1 signaling mediated cell-specific response to mechanical stimuli. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:576-583, 2018.

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“…Exogenous application of small magnitude mechanical regimes in the form of low intensity vibrations (LIV) ranging between 0.1-2g acceleration magnitudes and 20-200Hz frequencies were shown to be effective in improving bone and muscle indices in clinical and preclinical studies 17 . At the cellular level, our group has reported that application of LIV increases MSC contractility 18 , activates RhoA signaling 19 , and results in increased osteogenic differentiation and proliferation of MSCs 20 .…”

Section: Introductionmentioning

confidence: 99%

Low Intensity Vibration Restores Nuclear YAP Levels and Acute YAP Nuclear Shuttling in Mesenchymal Stem Cells Subjected to Simulated Microgravity

Thompson

Woods

Newberg

et al. 2020

Preprint

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27Reducing the bone deterioration that astronauts experience in microgravity requires 28 countermeasures that can improve the effectiveness of rigorous and time-expensive exercise 29 regimens under microgravity. The ability of low intensity vibrations (LIV) to activate force-30 responsive signaling pathways in cells suggests LIV as a potential countermeasure to improve 31 cell responsiveness to subsequent mechanical challenge. Mechanoresponse of mesenchymal 32 stem cells (MSC) that maintains bone-making osteoblasts is in part controlled by the 33 "mechanotransducer" protein YAP (Yes-associated protein) which is shuttled into the nucleus in 34 response cyto-mechanical forces. Here, using YAP nuclear shuttling as a measure of MSC 35 mechanoresponse, we tested the effect of 72 hours of simulated microgravity (SMG) and daily 36 LIV application (LIV DT ) on the YAP nuclear entry driven by either acute LIV (LIV AT ) or 37Lysophosphohaditic acid (LPA), applied at the end of the 72h period. We hypothesized that 38 SMG-induced impairment of acute YAP nuclear entry will be alleviated by daily application of 39 LIV DT . Results showed that while both acute LIV AT and LPA treatments increased nuclear YAP 40 entry by 50% and 87% over the basal levels in SMG-treated MSCs, nuclear YAP levels of all 41 SMG groups were significantly lower than non-SMG controls. Daily dosing of LIV DT , applied in 42 parallel to SMG, restored the SMG-driven decrease in basal nuclear YAP to control levels as 43 well as increasing the LPA-induced but not LIV AT -induced YAP nuclear entry over the non-LIV DT 44 treated, SMG only, counterparts. These cell level observations suggest that utilizing daily LIV DT 45 treatments is a feasible countermeasure for increasing the YAP-mediated anabolic 46 responsiveness of MSCs to subsequent mechanical challenge under SMG. 47 48

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Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness

Cited by 42 publications

References 59 publications

Mechanical impact stimulation platform tailored for high-resolution light microscopy

Mechanical impact stimulation platform tailored for high-resolution light microscopy

IGF‐1 signaling mediated cell‐specific skeletal mechano‐transduction

Low Intensity Vibration Restores Nuclear YAP Levels and Acute YAP Nuclear Shuttling in Mesenchymal Stem Cells Subjected to Simulated Microgravity

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