Function of the cytoskeleton in gravisensing during spaceflight

doi:10.1016/S0273-1177(03)90399-1

Advances in Space Research

Volume 32, Issue 8, October 2003, Pages 1585-1593

https://doi.org/10.1016/S0273-1177(03)90399-1 Get rights and content

Abstract

Since astronauts and cosmonauts have significant bone loss in microgravity we hypothesized that there would be physiological changes in cellular bone growth and cytoskeleton in the absence of gravity. Investigators from around the world have studied a multitude of bone cells in microgravity including Ros 17/2.8, Mc3T3-E1, MG-63, hFOB and primary chicken calvaria. Changes in cytoskeleton and extracellular matrix (ECM) have been noted in many of these studies. Investigators have noted changes in shape of cells exposed to as little as 20 seconds of microgravity in parabolic flight. Our laboratory reported that quiescent osteoblasts activated by sera under microgravity conditions had a significant 60% reduction in growth (p<0.001) but a paradoxical 2-folf increase in release of the osteoblast autocrine factor PGE₂ when compared to ground controls. In addition, a collapse of the osteoblast actin cytoskeleton and loss of focal adhesions has been noted after 4 days in microgravity.

Later studies in Biorack on STS-76, 81 and 84 confirmed the increased release of PGE₂ and collapse of the actin cytoskeleton in cells grown in microgravity conditions, however flown cells under 1g conditions maintained normal actin cytoskeleton and fibronectin matrix. The changes seen in the cytoskeleton are probably not due to alterations in fibronectin message or protein synthesis since no differences have been noted in microgravity. Multiple investigators have observed actin and microtubule cytoskeletal modifications in microgravity, suggesting a common root cause for the change in cell architecture. The inability of the Og grown osteoblast to respond to sera activation suggests that there is a major alteration in anabolic signal transduction under microgravity conditions, most probably through the growth factor receptors and/or the associated kinase pathways that are connected to the cytoskeleton. Cell cycle is dependent on the cytoskeleton. Alterations in cytoskeletal structure can block cell growth either in G1 (F-actin microfilament collapse), or in G2/M (inhibition of microtubule polymerization during G2/M-phase). We therefore hypothesize that microgravity would inhibit growth in either G1, or G2/M.

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¹: www.labofcellgrowth.com

View full text

Function of the cytoskeleton in gravisensing during spaceflight

Abstract

Bone

Matrix Biol

J Biotechnol

Exp Cell Res

J Biomech

Exp Cell Res

Cytoskeletal integrity is required throughout the mitogen stimulation phase of the cell cycle and mediates the anchorage-dependent expression of cyclin D1

Mol Biol Cell

Growth factor-induced signal transduction in adherent mammalian cells is sensitive to gravity

FASEB J

The effect of microgravity on morphology and gene expression of osteoblasts in vitro

FASEB J

Epidermal growth factorinduced expression of c-fos is influenced by altered gravity conditions

Aviat Space Environ Med

Microgravity decreases c-fos induction and serum response element activity

J. Cell Sci.

Transduction of mechanical strain in bone

ASGSB Bull

Mechanotransduction and the functional response of bone to mechanical strain

Calcif Tissue Int

Shape changes of osteoblastic cells under gravitational variations during parabolic flight-relationship with PGE2 synthesis

Cell Struct Funct

Rho GTPases and the actin cytoskeleton

Science

Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton

Philos Trans R Soc Lond B Biol Sci

Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle

Physiol Genomics