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

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 <i>COL1A1</i>, <i>COL1A2</i>, <i>COL3A1</i>, <i>POSTN</i>, <i>MMP13</i>, and <i>MMP14</i>, together with downregulation of key cartilage matrix genes, including <i>COL2A1</i>, <i>ACAN</i>, <i>CHAD</i>, and <i>CNMD</i>. 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.<h4>Conclusions</h4>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.