The combined effects of simulated microgravity and X-ray radiation on MC3T3-E1 cells and rat femurs

Abstract

Microgravity is well-known to induce Osteopenia. However, the combined effects of microgravity and radiation that commonly exist in space have not been broadly elucidated. This research investigates the combined effects on MC3T3-E1 cells and rat femurs. In MC3T3-E1 cells, simulated microgravity and X-ray radiation, alone or combination, show decreased cell activity, increased apoptosis rates by flow cytometric analysis, and decreased Runx2 and increased Caspase-3 mRNA and protein expressions. In rat femurs, simulated microgravity and X-ray radiation, alone or combination, show increased bone loss by micro-CT test and Masson staining, decreased serum BALP levels and Runx2 mRNA expressions, and increased serum CTX-1 levels and Caspase-3 mRNA expressions. The strongest effect is observed in the combined group in MC3T3-E1 cells and rat femurs. These findings suggest that the combination of microgravity and radiation exacerbates the effects of either treatment alone on MC3T3-E1 cells and rat femurs.

A Current Overview of the Biological Effects of Combined Space Environmental Factors in Mammals

“…Female BALB/cByJ 4-month-old mice were exposed to low dose and high LET silicon ion radiation (0.17 Gy single radiation, 0.5 Gy single radiation and fractionated radiation) under partial weightlessness (G/6 to simulate lunar gravity). It was noted that the combination of the two factors had a negative effect on the maintenance of bone mass by both reducing bone formation and increasing bone resorption, and the impaired bone formation response was related to the inhibited Wnt signaling ( Macias et al, 2016 ), the increased Runx2 and decreased Caspase-3 mRNA expression ( Dong et al, 2021 ). On the whole, most studies showed that microgravity-induced bone loss and impaired bone mechanical properties were aggravated by ionizing radiation exposure.…”

The effects of microgravity on bone structure and function

“…Congruent to spaceflight observations, most of the current literature consistently suggest that simulated-µG inhibits the proliferation and differentiation of MSC towards osteoblasts, despite using different methods of µG simulation (Table 5). This is indicated by the suppressed gene expression of osteoblast differentiation markers such as bone morphogenic protein (BMP) and Runt-related transcription factor 2 (Runx2) 18,[90][91][92][93][94][95][96][97][98][99][100][101] , in addition to the lowered expression of other osteoblastogenesis-related genes 18,97,99,[101][102][103] . The marker for osteoblast maturation from MSC progenitors -ALP, is also expressed at lower levels in preosteoblasts and osteoblasts exposed to various forms of simulated-µG [95][96][97]99,104 .…”

“…It is suggested that simulated-µG prevents extracellular calcium from entering osteoblasts, thus reducing intracellular free calcium levels which impairs calcium deposition and bone formation 102,106 . Furthermore, simulated-µG has been shown to cause cell cycle arrest at G2 and even induce apoptosis in osteoblasts 100,102 . HLUinduced bone loss in mice is consistently accompanied by a reduction in the number of viable osteoblasts and osteocytes in mice 107 .…”