Excess glucocorticoids inhibit murine bone turnover via modulating the immunometabolism of the skeletal microenvironment
Elevated bone resorption and diminished bone formation have been recognized as the primary features of glucocorticoid-associated skeletal disorders. However, the direct effects of excess glucocorticoids on bone turnover remains unclear. Here, we explored the outcomes of exogenous glucocorticoid treatment on bone loss and delayed fracture healing in mice and found that reduced bone turnover was a dominant feature, resulting in a net loss of bone mass. We investigated the single-cell gene expression profiles of these two models. In the glucocorticoid-induced bone loss model, we sequenced the cell population digested from the bone surface. In the glucocorticoid-associated fracture healing model, we sequenced the cell population digested from the callus. Overall, the cell population on the bone surface was predominantly composed of hematopoietic cells, while only a small fraction represented the bone progenitor cells. In the fracture healing model, the callus contained a significant number of osteogenic and osteoclastic lineage cells. We primarily analyzed the gene expression of functional genes in the fracture healing model and characterized the metabolic profiles. These data provide insights into the multifactorial metabolic mechanisms by which glucocorticoids generate skeletal disorders. Overall design: We utilized single-cell RNA-sequencing (scRNA-seq; 10x genomics) to investigate the principal cell types involved that modulate bone turnover during glucocorticoids exposure.