Decoding transcriptional, metabolic and cell death signatures in osteoarthritis and endemic osteoarthritis at single-cell resolution

The molecular differences between osteoarthritis (OA) and endemic OA (Kashin-Beck disease, KBD), have been investigated at bulk-level, inherently masking cellular heterogeneity and critical discriminative markers.We conducted single-cell RNA sequencing (scRNA-seq) on a total of 139,943 chondrocytes isolated from 17 human cartilage samples, including 3 healthy controls, 8 patients with OA, and 6 patients with KBD. Chondrocyte populations were identified and compared.

Differentially expressed gene, functional enrichment, metabolic activity, and cell death signature analyses were performed, with validation by immunohistochemistry staining and quantitative real-time PCR. We found that the preHTC, FC, preInfC, and InfC populations were enriched in OA, whereas ProC and HomC populations predominated in KBD. The HTC population, located in the deep cartilage zone, showed no major differences between the two diseases.