Effects of microgravity on cell cytoskeleton and embryogenesis

Crawford-Young, Susan J.

doi:10.1387/ijdb.052077sc

Cited by 147 publications

(104 citation statements)

References 73 publications

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“…These changes are likely due to the integrated signalling network that couples mechanosensitive receptors and pathways to gene and transcription modulation [38], and may furthermore be associated with structural adjustments on the cell level (e.g. actin cytoskeleton reorganization) [39].…”

Section: Discussionmentioning

confidence: 99%

TRPC6 in simulated microgravity of intervertebral disc cells

et al. 2018

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Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5 days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3 days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies.Graphical abstract These slides can be retrieved under Electronic Supplementary Material.

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Section: Discussionmentioning

confidence: 99%

TRPC6 in simulated microgravity of intervertebral disc cells

et al. 2018

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“…These phenotypes may relate to the effects of microgravity on the cytoskeleton (summarized in Crawford-Young, 2006). A further, not mutually exclusive, possibility is that the observed phenotypes could result from an altered proliferation of the anterior neural system.…”

Section: Microgravity Embryonic Stem Cells and Developmentmentioning

confidence: 99%

Microgravity, Stem Cells, and Embryonic Development: Challenges and Opportunities for 3D Tissue Generation

Andreazzoli

Angeloni

Broccoli

et al. 2017

Front. Astron. Space Sci.

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Space is a challenging environment for the human body, due to the combined effects of reduced gravity (microgravity) and cosmic radiation. Known effects of microgravity range from the blood redistribution that affects the cardiovascular system and the eye to muscle wasting, bone loss, anemia, and immune depression. About cosmic radiation, the shielding provided by the spaceship hull is far less efficient than that afforded at ground level by the combined effects of the Earth atmosphere and magnetic field. The eye and its nervous layer (the retina) are affected by both microgravity and heavy ions exposure. Considering the importance of sight for long-term manned flights, visual research aimed at devising measures to protect the eye from environmental conditions of the outer space represents a special challenge to meet. In this review we focus on the impact of microgravity on embryonic development, discussing the roles of mechanical forces in the context of the neutral buoyancy the embryo experiences in the womb. At variance with its adverse effects on the adult human body, simulated microgravity may provide a unique tool for understanding the biomechanical events involved in the development and assembly in vitro of three-dimensional (3D) ocular tissues. Prospective benefits are the development of novel safety measures to protect the human eye from cosmic radiation in microgravity during long-term manned spaceflights in the outer space, as well as the generation of human 3D-retinas with its supporting structures to develop innovative and effective therapeutic options for degenerative eye diseases.

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“…In addition to actin microfilaments and intermediate filaments, they form the cell skeleton (cytoskeleton) that gives shapes and biomechanical properties to the cells. Actin filaments and microtubules don't only constitute simple static structures; these fibers react, grow or shrink, forming that way dynamical structures that self-adapt to the changes of cell states-particularly changes of energy levels-and to the mechanical, electrical or magnetic exogenous stimuli (Vassilev et al 1982;Tabony 1994;Tabony and Job 1992a;Papaseit et al 2000;Glade andTabony 2002, 2005;Glade et al 2006;Crawford-Young 2006;Roesner et al 2006;Galimberti et al 2006;Kroupova et al 2007;Coleman et al 2007;Tabony et al 2007;Ingber 2008;Qian et al 2008;Yang et al 2008;Sieberer et al 2009;Qian et al 2009a, b). Microtubules get also involved in numerous cell functions, often constituting organelles: they form the centriole, the organizing center of the cell from which the microtubules radiate, the mitotic spindle that drives the chromosomal segregation during cell division, the elastic 'motorized arms' of cilia and flagella.…”

Section: Microtubulesmentioning

confidence: 99%

On the Nature and Shape of Tubulin Trails: Implications on Microtubule Self-Organization

Glade

2012

Acta Biotheor

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Microtubules, major elements of the cell skeleton are, most of the time, well organized in vivo, but they can also show self-organizing behaviors in time and/or space in purified solutions in vitro. Theoretical studies and models based on the concepts of collective dynamics in complex systems, reaction-diffusion processes and emergent phenomena were proposed to explain some of these behaviors. In the particular case of microtubule spatial self-organization, it has been advanced that microtubules could behave like ants, self-organizing by 'talking to each other' by way of hypothetic (because never observed) concentrated chemical trails of tubulin that are expected to be released by their disassembling ends. Deterministic models based on this idea yielded indeed like-looking spatio-temporal self-organizing behaviors. Nevertheless the question remains of whether microscopic tubulin trails produced by individual or bundles of several microtubules are intense enough to allow microtubule self-organization at a macroscopic level. In the present work, by simulating the diffusion of tubulin in microtubule solutions at the microscopic scale, we measure the shape and intensity of tubulin trails and discuss about the assumption of microtubule self-organization due to the production of chemical trails by disassembling microtubules. We show that the tubulin trails produced by individual microtubules or small microtubule arrays are very weak and not elongated even at very high reactive rates. Although the variations of concentration due to such trails are not significant compared to natural fluctuations of the concentration of tubuline in the chemical environment, the study shows that heterogeneities of biochemical composition can form due to microtubule disassembly. They could become significant when produced by numerous microtubule ends located in the same place. Their possible formation could play a role in certain conditions of reaction. In particular, it gives a mesoscopic basis to explain the collective dynamics observed in excitable microtubule solutions showing the propagation of concentration waves of microtubules at the millimeter scale, although we doubt that individual microtubules or bundles can behave like molecular ants.

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Effects of microgravity on cell cytoskeleton and embryogenesis

Cited by 147 publications

References 73 publications

TRPC6 in simulated microgravity of intervertebral disc cells

TRPC6 in simulated microgravity of intervertebral disc cells

Microgravity, Stem Cells, and Embryonic Development: Challenges and Opportunities for 3D Tissue Generation

On the Nature and Shape of Tubulin Trails: Implications on Microtubule Self-Organization

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