Single-cell sequencing reveals the immune microenvironment in osteoarthritis: from heterogeneity to therapeutic targets.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. Its pathophysiological mechanisms are shifting from the traditional "mechanical wear and tear" theory to the "immune-inflammatory driven" paradigm. The advent of single-cell RNA sequencing (scRNA-seq) technology has provided an unprecedented resolution for dissecting the complex immune microenvironment within OA joints. This review systematically summarizes the key advances of scRNA-seq in dissecting OA immunity, with a focus on the heterogeneity of immune cell subsets, maps the dynamic trajectory of immune cells from quiescence to activation, and reveals the complex ligand-receptor network between immune cells and joint-resident cells (synovial fibroblasts, chondrocytes, and subchondral osteoblasts). This study discusses the challenges and prospects of translating mechanistic insights into clinically viable diagnostic biomarkers and immunotherapeutic targets based on findings from scRNA-seq, and further deepens the understanding of the immune microenvironment in OA to advance clinical translation and lays a theoretical foundation for the development of precise diagnosis and treatment strategies targeting immune regulation.