FOXO1 modulates proliferation and apoptosis of chondrocytes isolated from developmental dysplastic hips

Developmental dysplasia of the hip (DDH) is a prevalent pediatric and adult hip disorder that leads to hip dysfunction, but its pathogenesis remains incompletely understood. The role of FOXO1, a key regulator of cell proliferation and apoptosis, in DDH chondrocyte homeostasis has not been thoroughly investigated. This study aimed to clarify FOXO1’s regulatory mechanism in DDH chondrocytes and evaluate its clinical diagnostic and prognostic value. We first performed transcriptomic analysis of the GSE169495 dataset to identify dysregulated genes in DDH chondrocytes. Then, we verified FOXO1 expression and function in human DDH chondrocytes using siRNA knockdown, flow cytometry (cell cycle/apoptosis), CCK-8 (proliferation), and RT-PCR. Finally, we analyzed clinical data from 120 DDH patients (40 mild/40 moderate/40 severe) and 60 healthy controls to assess FOXO1’s clinical utility. Transcriptomic analysis showed FOXO1 and its regulatory network (Akt1, Gsk3b) were persistently dysregulated in DDH chondrocytes. Functional assays confirmed FOXO1 inhibited proliferation via G0/G1 arrest (mediated by PCNA/Cyclin D1/p21 downregulation) and promoted apoptosis. Clinically, preoperative FOXO1 correlated negatively with DDH severity, showed high within-cohort diagnostic performance (AUC = 0.994, 95% CI 0.986–0.999), and predicted postoperative Harris score improvement. FOXO1 acts as a candidate regulator of DDH pathogenesis and a promising clinical biomarker within the studied cohort, providing a potential target for DDH diagnosis and treatment that warrants independent validation.