Mechanical unloading triggers glutamine influx and catabolism to suppress osteoclast apoptosis

External mechanical stimuli are pivotal for the maintenance of bone homeostasis via enhancing bone formation and inhibiting bone resorption. Lack of mechanical loading during prolonged bed rest or exposure to long-term microgravity environment in space leads to a rapid decline in bone mass and bone strength. Osteoblast lineage cells are capable of sensing and transmitting mechanical signals through a variety of pathways. However, the mechanisms by which osteoclasts perceive and respond to mechanical disturbances remain largely unclear. Here, through integrating the data of single-cell transcriptome, metabolome, proteome and ubiquitinome of bone tissues from hindlimb unloading (HLU) and control mice, we clarify that in the absence of mechanical force, osteoclasts are characterized by significant increase in Gln influx and catabolism, as well as suppression of intrinsic apoptosis. To investigate the mechanism of bone loss in weightlessnessrole, we utilized control and hindlimb unloading mice. To more fully understand the response of different cell types in bone tissue to weightlessness, we performed single-cell RNA-sequencing of control and hindlimb unloading mice at postnatal day 28.