Single-cell RNA sequencing reveals extensive fibrotic remodeling and pathogenic chondrocyte subpopulations in developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a common pediatric orthopedic disorder that predisposes affected children to early-onset osteoarthritis (OA), yet the cellular heterogeneity and fibrotic remodeling of acetabular cartilage are poorly understood. We performed single-cell RNA sequencing (scRNA-seq) on acetabular cartilage obtained from three children with DDH and two age-matched controls, thereby generating a transcriptomic atlas of 10,550 chondrocytes. Nine chondrocyte subpopulations were identified, including four previously unrecognized subsets (C1-C4). Compared with controls, DDH cartilage exhibited a marked shift toward fibrocartilage-like phenotypes, characterized by upregulation of fibrotic and matrix-remodeling genes, such as COL1A1, COL1A2, COL3A1, POSTN, MMP13, and MMP14, together with downregulation of key cartilage matrix genes, including COL2A1, ACAN, CHAD, and CNMD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed enrichment of extracellular matrix (ECM) organization and related pathways. Pseudotime analysis demonstrated a trajectory toward fibrotic and proliferative states, and CellChat analysis identified enhanced collagen and TGF-β signaling among fibrotic subsets. These transcriptional findings were validated by polymerase chain reaction (PCR), immunohistochemistry (IHC), and histological staining. These findings reveal molecular remodeling of cartilage obtained from dislocated hips in DDH and identify fibrosis-associated chondrocyte subpopulations that may contribute to early degenerative changes.