Single-cell RNA sequencing analysis dissected the osteo-immunology microenvironment and revealed key regulators in osteoporosis.

Osteoporoticfractures become increasingly common in postmenopausal women over age 55 years and men after age 65 years, bringing about substantial bone-associated morbidities, and augmented mortality and health-care costs. Advanced researches have led to a more accurate assessment of osteoporosis (OP) and have broadened the range of therapeutic approaches available to prevent osteoporotic fractures. Single-cell RNA sequencing (scRNA-seq) analysis is an evolutionary method that quantifies the majority of transcripts in individual cells at isoform resolution, paving the way for more detailed analyses of gene regulation in biology and medicine. We have extracted 19,102 cells and 4097 dynamical genes with significant expression changes. Several new subtypes of macrophages and differentially over-expressed genes were discovered in the trajectory of osteoclasts formation. The zinc finger protein 36, C3H type-like 1 (ZFP36L1) and defensin alpha 3 (DEFA3) were identified as novel bone metabolism-related genes. RETN-CAP1 was newly found to be involved in the interaction between osteoclasts and immunocytes, indicating that osteo-immunology microenvironment substantially contributed to the pathology of osteoporosis or osteopenia. In this research, we have performed Single-cell RNA sequencing analysis to display the trajectory of osteoclast formation and reveal the possible gene targets and signaling pathways that probably play an important role in osteoporosis.