Temporal effects of three-dimensional clinostat treatment on bone and serum metabolome in C57BL/J mice: a new method of simulating microgravity effect

Abstract

Microgravity is an unavoidable aspect of space flight. A three-dimensional (3D) clinostat is a great method to simulate the effects of microgravity on Earth. The impact of microgravity on plants, cells, and Caenorhabditis elegans has been extensively studied. However, no study has used a 3D clinostat apparatus to simulate the effects of microgravity on mouse models. Therefore, we conducted a study to produce a space microgravity mouse models using 3D clinostat treatment and explored the time effect of 3D clinostat treatment on the skeleton and metabolome of C57BL/J mice. Thirty 8-week-old male C57BL/J mice were randomly assigned to three groups: mice in individually ventilated cages (MC group, n = 6), mice in survival boxes (SB group, n = 12), and mice in survival boxes receiving 3D clinostat treatment (CS group, n = 12). Bone loss was assessed using microcomputed tomography of the left femur, whereas the changes in serum metabolites were monitored using untargeted metabolomics. A marked reduction in the trabecular number (p < 0.05) and an increased trabecular spacing (p < 0.1) were observed to occur in a time-dependent manner in the CS group compared with the SB group. Compared with the metabolome of the SB group, the metabolome of the CS group showed significant differences at Ⅰ and Ⅳ stages. Furthermore, the common pathways involved in differential metabolites in the Ⅰ and Ⅳ stages were valine, leucine, isoleucine degradation, and 2-oxocarboxylic acid metabolism. The KEGG pathways in the Ⅳ stages were mainly related to the nervous system, which was a result of microgravity.