Evaluation of the three-dimensional clinostat as a simulator of weightlessness

Hoson, Takayuki; Kamisaka, Seiichiro; Masuda, Yoshio; Yamashita, Masamichi; Buchen, Brigitte

doi:10.1007/pl00008108

Cited by 212 publications

(161 citation statements)

References 57 publications

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“…Control samples (1 g) were treated as those kept in the RPM and placed close to the RPM. In the RPM probes are fixed as close as possible to the center of two frames rotating one inside the other, driven by separate motors [13]. The rotation of each frame is random and autonomous under computer control.…”

Section: Methodsmentioning

confidence: 99%

Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals

Morbidelli

Monici²,

Marziliano

et al. 2005

Biochemical and Biophysical Research Communications

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Health hazards in astronauts are represented by cardiovascular problems and impaired bone healing. These disturbances are characterized by a common event, the loss of function by vascular endothelium, leading to impaired angiogenesis. We investigated whether the exposure of cultured endothelial cells to hypogravity condition could affect their behaviour in terms of functional activity, biochemical responses, morphology, and gene expression. Simulated hypogravity conditions for 72 h produced a reduction of cell number. Genomic analysis of endothelial cells exposed to hypogravity revealed that proapoptotic signals increased, while antiapoptotic and proliferation/survival genes were down-regulated by modelled low gravity. Activation of apoptosis was accompanied by morphological changes with mitochondrial disassembly and organelles/cytoplasmic NAD(P)H redistribution, as evidenced by autofluorescence analysis. In this condition cells were not able to respond to angiogenic stimuli in terms of migration and proliferation. Our study documents functional, morphological, and transcription alterations in vascular endothelium exposed to simulated low gravity conditions, thus providing insights on the occurrence of vascular tissue dysregulation in crewmen during prolonged space flights. Moreover, the alteration of vascular endothelium can intervene as a concause in other systemic effects, like bone remodelling, observed in weightlessness. Ó 2005 Elsevier Inc. All rights reserved.Keywords: Endothelial cell; Hypogravity; Gene expression; Autofluorescence; Apoptosis; Angiogenesis; Migration; Proliferation Angiogenesis, a process which leads to formation of new vessels, has a relevant physiological role during development and in the adult life [1,2]. Endothelial cells are the true player of the angiogenesis process. Several cardiovascular pathologies are caused by endothelial dysfunction (myocardial ischemia, atherosclerosis), thus growth factors and strategies able to restore the integrity of the endothelium and to promote angiogenesis can be viewed as innovative therapeutic approaches [3,4].Indications that mechanical stimulation of cells, and endothelium in particular, is able to change some of their functions at biochemical and molecular level are reported in the literature [5]. In spite of the evidence that cells are sensitive to mechanical stimuli, the molecular mechanisms by which individual cells recognize and respond to external forces are not well understood. Our interest on hypogravity originates from the recognition that several disturbances associated to endothelium-0006-291X/$ -see front matter Ó

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Section: Methodsmentioning

confidence: 99%

Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals

Morbidelli

Monici²,

Marziliano

et al. 2005

Biochemical and Biophysical Research Communications

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“…5a, b. In 1986 Japanese researchers developed the first modern version of a 3D clinostat used initially for plant research (Murakami and Yamada 1988;Hoson et al 1992Hoson et al , 1997. In 1994 the notion of "true random positioning" was advocated by Dr. D Mesland of the European Space Agency, ESA (Mesland 1996).…”

Section: D Random Modementioning

confidence: 99%

Technology and Developments for the Random Positioning Machine, RPM

Borst¹,

Loon

2008

Microgravity Sci. Technol.

209

197

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A Random Positioning Machine (RPM) is a laboratory instrument to provide continuous random change in orientation relative to the gravity vector of an accommodated (biological) experiment. The use of the RPM can generate effects comparable to the effects of true microgravity when the changes in direction are faster than the object's response time to gravity. Thus, relatively responsive living objects, like plants but also other systems, are excellent candidates to be studied on RPMs. In this paper the working principle, technology and control modes will be explained and an overview of the previously used and available experiment systems will be presented. Current and future developments like a microscope facility or fluid handling systems on the RPM and the option to provide partial gravity control modes simulating for instance Mars or Moon gravity will be discussed.

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“…In the RPM, introduced by Hoson et al [1997], probes are fixed as close as possible to the center of two frames rotating one inside the other, driven by separate motors. The rotation of each frame is random and autonomous under computer control.…”

Section: Random Positioning Machinementioning

confidence: 99%

Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

et al. 2006

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Gravity acts permanently on organisms as either static or dynamic stimulation. Understanding the influence of gravitational and mechanical stimuli on biological systems is an intriguing scientific problem. More than two decades of life science studies in low g, either real or modeled by clinostats, as well as experimentation with devices simulating different types of controlled mechanical stimuli, have shown that important biological functions are altered at the single cell level. Here, we show that the human leukemic line FLG 29.1, characterized as an osteoclastic precursor model, is directly sensitive to gravitational unloading, modeled by a random positioning machine (RPM). The phenotypic expression of cytoskeletal proteins, osteoclastic markers, and factors regulating apoptosis was investigated using histochemical and immunohistochemical methods, while the expression of the corresponding genes was analyzed using RT-PCR. A quantitative bone resorption assay was performed. Autofluorescence spectroscopy and imaging were applied to gain information on cell metabolism. The results show that modeled hypogravity may trigger both differentiation and apoptosis in FLG 29.1 cells. Indeed, when comparing RPM versus 1 Â g cultures, in the former we found cytoskeletal alterations and a marked increase in apoptosis, but the surviving cells showed an osteoclastic-like morphology, overexpression of osteoclastic markers and the ability to resorb bone. In particular, the overexpression of both RANK and its ligand RANKL, maintained even after return to 1 Â g conditions, is consistent with the firing of a differentiation process via a paracrine/autocrine mechanism. J. Cell. Biochem. 98: 65-80, 2006. ß 2005 Wiley-Liss, Inc.Key words: weightlessness; preosteoclastic differentiation; apoptosis; bone resorption; osteoporosis; gene expressionThe importance of gravity in modulating some biological processes, such as plant gravitropism and the adaptation of the vertebrate skeleton in relation to its load-bearing function, has long been known. Nevertheless, the role of gravity and other mechanical factors in biological processes is far from clear. A weightless environment is a powerful tool for understanding this role and for studying the related cellular and molecular mechanisms. Several investigations conducted in space laboratories and with instruments averaging the gravity vector, and thus simulating conditions of reduced gravity, have shown that isolated cells may change their behavior under altered gravitational conditions. Loss of cell activation [Cogoli et al., 1984], perturbation of signal transduction [Schmitt et al., 1996;Hashemi et al., 1999] and modification of genetic expression [Walther et al., 1998;Hammond et al., 1999] have been described. This suggests that some of the mechanisms at the roots of the systemic effects observed in weightlessness, such as depression of the immune system [Gmü nder and Cogoli, 1996]

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Evaluation of the three-dimensional clinostat as a simulator of weightlessness

Cited by 212 publications

References 57 publications

Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals

Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals

Technology and Developments for the Random Positioning Machine, RPM

Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

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