Single-cell RNA-sequencing analysis reveals the molecular mechanism of subchondral bone cell heterogeneity in the development of osteoarthritis

Abstract

The cellular composition and underlying spatiotemporal transformation processes of subchondral bone in osteoarthritis (OA) remain unknown. Herein, various cell subsets from tibial plateau of patients with OA are identified, and the mechanism of subchondral microstructure alteration is elaborated using single-cell RNA sequencing technique. We identified two novel endothelial cell (EC) populations characterised by either exosome synthesis and inflammation response or vascular function and angiogenesis. Three osteoblast (OB) subtypes are introduced, separately related to vascularisation, matrix manufacturing and matrix mineralisation. The distinct roles and functions of these novel phenotypes in OA development are further discussed as well as interaction network between these subpopulations. The variation tendency of each population is testified in a destabilisation of the medial meniscus mouse model. The identification of cell types demonstrates a novel taxonomy and mechanism for ECs and OBs inside subchondral bone area provides new insights into the physiological and pathological behaviours of subchondral bone in OA pathogenesis.