Glucocorticoid-induced expansion of classical monocytes contributes to bone loss

Classical monocytes are commonly involved in the innate inflammatory response and are the progenitors of osteoclasts. Excess endogenous glucocorticoids (GCs) can increase the levels of classical monocytes in blood and bone marrow. The role of this cell population in high-dose exogenous GC-induced osteoporosis (GIOP) remains to be elucidated. In this study, GIOP was established in rats and mice by daily methylprednisolone injection, and monocyte subsets were analyzed by flow cytometry. We demonstrated that classical monocytes accumulate in bone marrow during GIOP. Similarly, the monocyte proportion among bone marrow nucleated cells was also increased in patients with steroid treatment history. We sorted classical monocytes and analyzed their transcriptional profile in response to GCs by RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that classical monocytes isolated from GC-treated rats exhibited osteoclast differentiation potential. Deletion of classical monocytes by clodronate liposome treatment prevented GIOP via inhibition of osteoclastogenesis and restoration of CD31 Hi endomucin Hi vessels. Regarding the molecular mechanism, classical monocytes express high levels of glucocorticoid receptors. In vitro treatment with GCs increased both the percentage and absolute number of monocytes and promoted their proliferation. In summary, classical monocytes mediated GC-induced bone loss and are a potential target for therapeutic intervention in GIOP treatment. Osteoporosis: Steroid-induced bone loss fueled by immune cell activity Immune cells involved in innate inflammatory responses are key mediators of steroid-induced osteoporosis, a finding that could inform development of new therapies for this common bone disease. Pei Liu from Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, China, and colleagues studied the role of immune cells known as classical monocytes in rodent models of steroid-induced osteoporosis. The researchers showed that the monocytes express receptors for the steroid hormone, which results in promoting their proliferation. The immune cells then accumulate in the bone marrow, where they spur bone degradation. Experimental depletion of the monocytes helped reduce steroid-triggered bone loss in mice by preventing bone resorption and eliciting growth of blood vessels that support bone formation. The authors suggest that similar therapeutic strategies could be of promise in humans.