Up-regulation of Ifi27l2a expression in bone marrow monocytes contributes to glucocorticoid-induced bone loss.

Glucocorticoid-induced osteoporosis (GIO) is the most common complication of prolonged, high-dose glucocorticoid therapy. The enhancement of osteoclast differentiation is a key factor in the pathogenesis of GIO. Osteoclasts originate from the bone marrow, and a disorder of the bone marrow microenvironment is closely linked to the development of GIO. However, alterations in the components and RNA transcripts of bone marrow cells during GIO remain unclear. Here, we perform single-cell analysis and report that the expansion of monocytes is a characteristic alteration in the bone marrow of GIO mice, accompanied by monocyte-biased hematopoiesis. The expression of Ifi27l2a is significantly upregulated in bone marrow cells from GIO mice, particularly within monocyte clusters. We demonstrate that Ifi27l2a plays a crucial role in the enhancement of osteoclast differentiation induced by glucocorticoid in vitro and in vivo experiments. Furthermore, we perform bioinformatics analysis of bone marrow cell clusters and monocyte subclusters in GIO mice. This study provides insights into the molecular mechanisms underlying osteoclast differentiation in bone marrow monocytes during GIO and suggests a potential therapeutic target.