Dysregulated Mechanotransduction via CCNB2 Underlies Fibroblast Hypoplasia in Developmental Dysplasia of the Hip

Purpose: Developmental dysplasia of the hip (DDH) involves structural and functional impairments in the joint capsule; however, the molecular mechanisms underlying these changes remain unclear. This study aimed to identify biomarkers associated with fibroblast mechanical signaling in the joint capsule of patients with DDH and explore their potential roles in disease pathogenesis. Methods: Joint capsule tissues were collected from DDH patients and age‐ and sex‐matched healthy controls. RNA sequencing (RNA-seq) identified differentially expressed cell-cell mechanical communication-related genes (DE-CMRGs). Five bioinformatics algorithms (MCC, MNC, Degree, Closeness, and Eccentricity) were applied to identify key biomarkers from DE-CMRGs correlated with fibroblast function. Biomarker validation was performed using reverse transcription quantitative PCR (RT-qPCR), Western blot, immunohistochemistry (IHC), and hematoxylin-eosin (HE) staining. Additionally, immune infiltration analysis and regulatory network construction (TF-mRNA and lncRNA-miRNA-mRNA ceRNA networks) were conducted to elucidate potential regulatory mechanisms. Results: Transcriptomic analysis revealed 155 DE-CMRGs, from which five biomarkers (KIF20A, BUB1, CCNB2, AURKB, and BUB1B) were identified. These biomarkers were significantly downregulated in DDH samples. Functional enrichment analyses highlighted their involvement in pathways related to muscle contraction, extracellular matrix interactions, cell cycle regulation, and immune responses. Immune infiltration analysis showed correlations between biomarkers and specific immune cell populations, particularly memory-activated CD4 T cells, macrophages, neutrophils, dendritic cells, and monocytes. Experimental validation confirmed that CCNB2 was significantly downregulated at both mRNA and protein levels in DDH tissues compared with controls. Histopathological examinations revealed reduced fibroblast density and altered cellular architecture associated with decreased CCNB2 expression. Conclusion: This study identifies and validates novel biomarkers, particularly CCNB2, associated with mechanical communication in joint capsule fibroblasts in DDH. These biomarkers, together with their related immune and regulatory networks, offer new insights into DDH pathogenesis and highlight potential targets for early diagnosis and therapeutic intervention.