Continuous Exposure to Simulated Hypergravity-Induced Changes in Proliferation, Morphology, and Gene Expression of Human Tendon Cells

Abstract

Gravity influences physical and biological processes, especially during development and homeostasis of several tissues in the human body. Studies under altered gravity have been receiving great attention toward a better understanding of microgravity-, hypogravity (<1 g)-, or hypergravity (>1 g)-induced alterations. In this work, the influence of simulated hypergravity over human tendon-derived cells (hTDCs) was studied at 5, 10, 15, and 20 g for 4 or 16 h, using a large diameter centrifuge. Main results showed that 16 h of simulated hypergravity limited cell proliferation. Cell area was higher in hTDCs cultured at 5, 10, and 15 g for 16 h, in comparison to 1 g control. Actin filaments were more pronounced in hTDCs cultured at 5 and 10 g for 16 h. Focal adhesion kinase (FAK) was mainly expressed in focal adhesion sites upon hypergravity stimulation, in comparison to perinuclear localization in control cells after 16 h; and FAK number/cell increased with increasing g-levels. A tendency toward an upregulation of tenogenic markers was observed; scleraxis (SCX), tenascin C (TNC), collagen type III (COL3A1), and decorin (DCN) were significantly upregulated in hTDCs cultured at 15 g and COL3A1 and DCN were significantly upregulated in hTDCs cultured at 20 g. Overall, simulated hypergravity affected the behavior of hTDCs, with more pronounced effects in the long-term period (16 h) of stimulation.

Gravitational Influence on Human Living Systems and the Evolution of Species on Earth

“…In a similar study, an increase in actin fiber density, but not in number, was pointed even in low g forces [ 59 ]. The results of both studies are in accordance with even more recent research performed on human tendon cells, cultured in 15–20 g for 16 h [ 60 ].…”

“…In a similar study, an increase in actin fiber density, but not in number, was pointed even in low g forces [59]. The results of both studies are in accordance with even more recent research performed on human tendon cells, cultured in 15-20 g for 16 h [60]. Bradamante et al (2018) studied osteogenic stem cell differentiation in microgravity in order to discover how human bone marrow stem cells (hBMSCs) react to a two week exposure in ISS when treated with the osteo-inducer 1,25-dihydroxy vitamin D. Their results provide evidence of cell cycle arrest, although without any indications of adipogenesis, senescence and apoptosis.…”

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

“…Until now, a number of studies were carried out under simulated conditions of unnatural gravity using ground-based facilities such as clinostats, random positioning machines, bioreactors, and parabolic flights for simulated microgravity (sµg) research [298][299][300], and well-designed centrifuges for hyper-gravity experiments [301,302]. Some real microgravity (µg) investigations were conducted in space on the International Space Station or onboard sounding rockets [303].…”

Transcriptomic Analysis of Planarians under Simulated Microgravity or 8 g Demonstrates That Alteration of Gravity Induces Genomic and Cellular Alterations That Could Facilitate Tumoral Transformation

“…At the cellular level, it has been shown that microgravity alters the structure of cells, as well as their apoptotic and mitotic responses [6,7,8]. Hypergravity also has a relevant impact in cells behavior and gene expression [10,11,12,13]. However, specific modifications in gene expression, gene products, and related structural-functional phenotypic diversification due to sustained changes in gravity conditions remain poorly understood.…”