Mechanisms of Gravitational Sensitivity of Osteogenic Precursor Cells

Буравкова, Л. Б.; Gershovich, Pavel; Gershovich, J. G.; Григорьев, А. И.

doi:10.32607/20758251-2010-2-1-28-35

Cited by 22 publications

(14 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under low gravity environment, actin stress fibers are reduced in number, length, and thickness (178, 179). Actin is often redistributed and has either a more perinuclear or more cortical localization (180, 181). Focal adhesion proteins no longer align well with the stress fibers; instead, they appear as bigger clusters without radial orientation in the cortical layer, resulting in reduced cell spreading (15).…”

Section: Cytoskeletonmentioning

confidence: 99%

Mechanotransduction as an Adaptation to Gravity

Najrana

Sanchez‐Esteban

2016

Front. Pediatr.

View full text Add to dashboard Cite

Gravity has played a critical role in the development of terrestrial life. A key event in evolution has been the development of mechanisms to sense and transduce gravitational force into biological signals. The objective of this manuscript is to review how living organisms on Earth use mechanotransduction as an adaptation to gravity. Certain cells have evolved specialized structures, such as otoliths in hair cells of the inner ear and statoliths in plants, to respond directly to the force of gravity. By conducting studies in the reduced gravity of spaceflight (microgravity) or simulating microgravity in the laboratory, we have gained insights into how gravity might have changed life on Earth. We review how microgravity affects prokaryotic and eukaryotic cells at the cellular and molecular levels. Genomic studies in yeast have identified changes in genes involved in budding, cell polarity, and cell separation regulated by Ras, PI3K, and TOR signaling pathways. Moreover, transcriptomic analysis of late pregnant rats have revealed that microgravity affects genes that regulate circadian clocks, activate mechanotransduction pathways, and induce changes in immune response, metabolism, and cells proliferation. Importantly, these studies identified genes that modify chromatin structure and methylation, suggesting that long-term adaptation to gravity may be mediated by epigenetic modifications. Given that gravity represents a modification in mechanical stresses encounter by the cells, the tensegrity model of cytoskeletal architecture provides an excellent paradigm to explain how changes in the balance of forces, which are transmitted across transmembrane receptors and cytoskeleton, can influence intracellular signaling pathways and gene expression.

show abstract

Section: Cytoskeletonmentioning

confidence: 99%

Mechanotransduction as an Adaptation to Gravity

Najrana

Sanchez‐Esteban

2016

Front. Pediatr.

View full text Add to dashboard Cite

show abstract

“…It has been consistently observed, however, that bone cells exposed to real microgravity display major alterations of their cytoskeleton integrity (3)(4)(5). Cytoskeleton integrity is essential for a variety of cell processes, such as proliferation, migration, signal transduction, apoptosis (6,7), fibrillogenesis, and differentiation (8). The cytoskeleton is responsive to changes in the mechanical environment because it is physically connected to the extracellular matrix through focal adhesions (FAs).…”

mentioning

confidence: 99%

Rac1 GTPase silencing counteracts microgravity‐induced effects on osteoblastic cells

et al. 2014

View full text Add to dashboard Cite

Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras homology (Rho) family. We investigated the effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under microgravity conditions. Human MG-63 osteoblastlike cells silenced for RhoGTPases were cultured in the automated Biobox bioreactor (European Space Agency) aboard the Foton M3 satellite and compared to replicate ground-based controls. The cells were fixed after 69 h of microgravity exposure for postflight analysis of focal contacts, F-actin polymerization, vascular endothelial growth factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did not affect sensitivity to microgravity but that Rac1 and, to a lesser extent, Cdc42 abrogation was particularly efficient in counteracting the spaceflight-related reduction of the number of focal contacts [؊50% in silenced, scrambled (SiScr) controls vs. ؊15% for SiRac1], the number of F-actin fibers (؊60% in SiScr controls vs. ؊10% for SiRac1), and the depletion of matrix-bound VEGF (؊40% in SiScr controls vs. ؊8% for SiRac1). Collectively, these data point out the role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated signaling pathways as potential targets for counteracting microgravity effects.-Guignandon, A., Faure, C., Neutelings, T., Rattner, A., Mineur, P., Linossier, M.-T., Laroche, N., Lambert, C., Deroanne, C., Nusgens, B., Demets, R., Colige, A., Vico, L. Rac1 GTPase silencing counteracts microgravityinduced effects on osteoblastic cells. FASEB J. 28, 4077-4087 (2014). www.fasebj.org

show abstract

“…Interestingly, we found the formation of numerous nascent lipid droplets in rBMSCs on PEI and PEU surface, which indicates the early adipogenic differentiation without any additional induction. Previous studies have suggested that adipogenesis could be triggered by high cell density and cytoskeleton reorganization [4,5,20,31,46]. In the present study, the high cell density was excluded as the possible reason for adipogenesis since on both PEU and PEI surfaces the cell densities were sparse and lower than that on TCP when the differentiation occurred.…”

Section: Discussionmentioning

confidence: 61%

“…The morphological change might be one of the factors for driving the spontaneous differentiation. It was suggested that cell shape might regulate the dedicated adipogenic/osteogenic MSCs fate decisions [5,31]. The different cytoskeleton rearrangement might influence the cell spreading and cellular conformation, the signal of which could be further transferred into the nucleus and alter the gene transcription of cells, which might result in the outcome of spontaneous adipogenesis [12].…”

Section: Discussionmentioning

confidence: 99%

Cultivation and spontaneous differentiation of rat bone marrow-derived mesenchymal stem cells on polymeric surfaces

Kratz

Wang

et al. 2013

Clinical Hemorheology and Microcirculation

View full text Add to dashboard Cite

Accumulating evidence demonstrated many physical and chemical cues from the local microenvironment could influence mesenchymal stem cells (MSCs) maintenance and differentiation. In this study, we systematically investigated the interaction of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and polymeric substrates. Adhesion, proliferative capacity, cytoskeleton alteration, cytotoxicity, apoptosis, senescence, and adipogenesis potential of rBMSCs were determined on these polymeric inserts prepared from polyetherurethane (PEU) and poly(ether imide) (PEI). Inserts for culture plates were applied to ensure that the rBMSCs were solely in contact to the tested material. The explored inserts exhibited advancing contact angles of 84 • (PEU) and 93 • (PEI). Finally, the micromechanical properties determined by atomic force microscopy (AFM) indentation varied in the range from 6 GPa (PEU) to 13 GPa (PEI). We found that both PEU and PEI showed a good cell compatibility to rBMSCs. rBMSCs could adherent on both polymeric surfaces with the similar adhesion ratio and subsequent division rate. However, cells cultured on PEU exhibited higher apoptosis level and senescence ratio, which resulted in lower cell density (22061 ± 3000/cm 2 ) compared to that on PEI (68395 ± 8000/cm 2 ) after 20 days cultivation. Morphological differences of rBMSCs were detected after 5 days cultivation. Cells on PEU exhibited flat and enlarged shape with rearranged filamentous actin (F-actin) cytoskeleton, while cells on PEI and tissue culture plate (TCP) had similar spindle-shape morphology and oriented F-actin. After 20 days, lipid droplets were spontaneously formed in rBMSCs on PEU and PEI but not on TCP. Both PEU and PEI might trigger rBMSCs towards spontaneous adipogenic commitment, whereas PEI provided better cell compatibility on rBMSCs apoptosis, senescence and proliferation.

show abstract

Mechanisms of Gravitational Sensitivity of Osteogenic Precursor Cells

Cited by 22 publications

References 91 publications

Mechanotransduction as an Adaptation to Gravity

Mechanotransduction as an Adaptation to Gravity

Rac1 GTPase silencing counteracts microgravity‐induced effects on osteoblastic cells

Cultivation and spontaneous differentiation of rat bone marrow-derived mesenchymal stem cells on polymeric surfaces

Contact Info

Product

Resources

About