Single-cell transcriptomics reveals chondrocyte state transitions and ECM remodeling in osteoarthritic knee cartilage

Authors

Bo, Z., Xu, H., Liang, Y.

Abstract

Osteoarthritis cartilage has heterogeneous chondrocyte states, yet their transitions remain unresolved from public single-cell data. We retrospectively reanalyzed a public knee cartilage single-cell RNA-seq dataset GSE255460 from 8 osteoarthritis and 3 non-osteoarthritis donors totaling 19 samples. After sample-wise quality control and doublet removal we performed batch-corrected clustering, chondrocyte subclustering with marker-based annotation, and trajectory inference using Slingshot. Regulatory chondrocytes were tested for osteoarthritis versus control differential expression, followed by Gene Ontology and KEGG enrichment with Benjamini-Hochberg false discovery rate <0.05, and protein-protein interaction hub screening. We retained 27,036 cells. Chondrocytes exhibited branching continuous states; regulatory cells localized near the main manifold and adjacent to inferred branches, suggesting a transition-adjacent state. In regulatory cells, osteoarthritis-upregulated genes were enriched for collagen-containing extracellular matrix organization, endoplasmic reticulum secretory/proteostasis, cell-matrix adhesion including focal adhesion, and TGFbeta/SMAD signaling. Protein-protein interaction analysis identified five high-connectivity hubs: COL5A1, COL5A2, COL6A1, COL1A2, and COL3A1. Our findings support a transition-adjacent regulatory program in OA with coordinated extracellular matrix remodeling and secretory/adhesion/TGFbeta signatures, nominating collagen hubs for validation.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 30 Jun 2026.

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