Deciphering chondrocyte diversity in diabetic osteoarthritis through single-cell transcriptomics

Abstract

The pathophysiological distinctions between osteoarthritis (OA) and diabetic osteoarthritis (DOA) are critical yet not well delineated. In this study, we employed single-cell RNA sequencing to clarify the unique cellular and molecular mechanisms underpinning the progression of both conditions. We identified a novel subpopulation of chondrocytes in DOA, termed 'Heat Shock' chondrocytes, marked by the expression of distinct molecular markers including HSPA1A, HSPA1B, HSPB1, and HSPA8. Our comprehensive gene expression analysis revealed a pronounced upregulation of inflammatory pathways associated with oxidative stress—namely the MAPK, NF-κB, and PI3K signaling pathways—in the effector and proliferating chondrocyte subpopulations, with a predominance in DOA. Further, our investigation into cell-cell communication demonstrated a significant diminution of intercellular signaling in DOA compared to OA. These insights not only elucidate distinct cellular heterogeneities and potential pathogenic mechanisms differentiating OA from DOA but also enhance our understanding of their molecular pathophysiology, offering novel avenues for targeted therapeutic strategies.