Conditioned Media from Microvascular Endothelial Cells Cultured in Simulated Microgravity Inhibit Osteoblast Activity

Abstract

Background and Aims. Gravity contributes to the maintenance of bone integrity. Accordingly, weightlessness conditions during space flight accelerate bone loss and experimental models in real and simulated microgravity show decreased osteoblastic and increased osteoclastic activities. It is well known that the endothelium and bone cells cross-talk and this intercellular communication is vital to regulate bone homeostasis. Because microgravity promotes microvascular endothelial dysfunction, we anticipated that the molecular cross-talk between endothelial cells exposed to simulated microgravity and osteoblasts might be altered. Results. We cultured human microvascular endothelial cells in simulated microgravity using the rotating wall vessel device developed by NASA. Endothelial cells in microgravity show growth inhibition and release higher amounts of matrix metalloproteases type 2 and interleukin-6 than controls. Conditioned media collected from microvascular endothelial cells in simulated microgravity were used to culture human osteoblasts and were shown to retard osteoblast proliferation and inhibit their activity. Discussion. Microvascular endothelial cells in microgravity are growth retarded and release high amounts of matrix metalloproteases type 2 and interleukin-6, which might play a role in retarding the growth of osteoblasts and impairing their osteogenic activity. Conclusions. We demonstrate that since simulated microgravity modulates microvascular endothelial cell function, it indirectly impairs osteoblastic function.

Spaceflight Induced Disorders: Potential Nutritional Countermeasures

“…Actin rearrangements of endothelia l cells (Siamwala et al, 2010) Changes in vasoresponsiveness (White et al, 2010) Heart Arrhythmias (Respress et al, 2014) Myocardial abnormalities (Liang et al, 2020) casein kinase-2 interacting protein-1 (CKIP-1) as a Suppressor of cardiac remodeling under microgravity (Ling et al, 2018) Changes of mitochondria, ribosornes, and endoplasmic reticulum in cardiomyocytes (Feger et al, 2016) Impairment of neural crest-derived cardiac structures with alterations in the autonomic nervous system (Hatzistergos et al, 2018) Bone Involvement of matrix metalloproteases type 2 and interleukin-6 in the defect of osteogenesis (Cazzaniga et al, 2014). Role of miR-494 in the defect of osteogenesis (Qin et al, 2019).…”

“…Interestingly, in microgravity, rapamycin induces transcriptional activation of blood-derived stem cells towards osteogenic differentiation by influencing bone formation (Gambacurta et al, 2019). Moreover, due to the delay of microvascular endothelial cell growth and the release of a high amounts of matrix metalloproteases type 2 and interleukin-6, the growth of osteoblasts is retarded and their osteogenic activity is impaired (Cazzaniga et al, 2014). Also miR-494 is correlated with a decrease in osteogenesis due to a marked reduction in osteoblast differentiation genes (Qin et al, 2019).…”

Culture of human cells in experimental units for spaceflight impacts on their behavior

“…[13][14][15][16] We have also shown that microvascular endothelial cells in simulated microgravity release proteins that affect osteoblast behavior in a co-culture system. 17 Recently, both macrovascular 18 and microvascular endothelial cells were flown to the International Space Station (ISS), which offers unique opportunities to study the effect of space on the cells.…”

Scalable Microgravity Simulator Used for Long-Term Musculoskeletal Cells and Tissue Engineering

“…Among the bioreactors, the rotating wall vessel (RWV), a suspension culture system that permits the cultivation of cells under low physiological fluid shear conditions, has been widely utilized [ 5 , 6 ]. The RWV requires to grow adherent cells on microcarrier beads so that they rotate at the same speed of the vessel wall around a horizontal axis, a condition that produces a vector-averaged gravity comparable with that of the near-earth free-fall orbit [ 7 ].…”