The Impact Of Sema3A On Bone Loss Under Simulated Gravity Changes

Microgravity during space flight will seriously endanger the normal physiological system of the human body.Osteoporosis caused by bone metabolism disorder is one of the main risks faced by astronauts in microgravity.The main mechanism of osteoporosis is due to the broken balance between osteoclasts and osteoblasts,that is,the enhanced function of osteoclasts,weakened function of osteoblasts,osteolysis greater than synthesis,and loss of bone mass.As research progressed,endothelial cells（ECs）were found to be highly sensitive to gravity,and angiogenesis has been shown to be closely associated with new bone formation,indicating an interaction between endothelial cells and bone cells.Studies have shown that Sema3 A has a regulatory effect on bone metabolism,which includes two aspects:on the one hand,Sema3 A inhibits the differentiation and function of osteoclasts.This can slow down the osteopenia caused by bone resorption;On the other hand,Sema3 A promotes the differentiation and function of osteoblasts,which makes up for the decrease of osteoblasts and promotes bone formation.So the absence of Sema3 A can lead to osteoporosis.Therefore,we believe that microgravity or hypergravity will cause changes in Sema3 A expression,and the results under the two conditions should be the opposite,that is,the decrease of Sema3 A expression in microgravity leads to osteoporosis,and the increase of Sema3 A in hypergravity state leads to bone sclerosis.The purpose of this study was to investigate the changes of Sema3 A expression in microgravity and hypergravity,and explore the mechanism of Sema3 A in bone mass loss induced by microgravity,so as to provide effective countermeasures for preventing osteoporosis in astronauts during space activities.In this paper,mouse lymphocyte endothelial cells and mouse vascular endothelial cells are selected as research objects in vitro experiments,and cell models are established under the simulated hypergravity state.First,the effects of cell cycle and apoptosis of the two cells in the hypergravity state were detected by flow cytometry.Then,western blot and real-time fluorescent quantitative PCR were used to detect the effects of Sema3 A,M-CSF and RANKL on protein and gene expression in the control group and ultra-recombinant cells.In animals,hind limb unloading（HLU）method was used to simulate microgravity to establish mouse osteoporosis model,and Mico-CT was used to detect the osteoporosis in mice.Then the content changes of Sema3 A,M-CSF and RANKL in the blood of osteoporosis mice were detected.The results showed that hypergravity did not affect apoptosis of mouse lymphocytes and mouse vascular endothelial cells in vitro,but affected cell cycle growth.Moreover,under the hypergravity condition,the contents of Sema3 A in both cells were higher than that in the control group（and the increasing trend of Sema3 A content in mouse vascular endothelial cells was more significant）,which caused a significant decrease of RANKL content.The results of the established animal model showed that most of the weightless mice had osteoporosis.In addition,the content of Sema3 A in mice with osteoporosis was significantly decreased,and the increase of RANKL and M-CSF contents（the increase of RANKL was more significant）.To sum up,under the hypergravity condition,the expression of Sema3 A in cells was increased,and the level of Sema3 A was significantly reduced under the microgravity condition.Osteoporosis caused by microgravity was closely related to the down-regulation of Sema3 A.