Phd2 Orchestrates Condylar Fracture Repair In Mice

Condylar fractures pose significant clinical challenges due to risks of malunion and functional impairment, necessitating deeper understanding of molecular repair mechanisms. Prolyl hydroxylase 2 (PHD2), a hypoxia-sensing regulator is implicated in skeletal repair, yet its interplay in condylar fracture healing remains unexplored. This study investigates PHD2’s role in regulating PDGF-BB secretion by osteocytes to balance osteogenesis and chondrogenesis during mandibular condylar fracture repair. A murine condylar fracture model was established without fixation, with healing monitored via micro-CT, histology (H&E, Masson), and immunofluorescence at postoperative days 14, 21, and 28. PHD2 inhibition was achieved using intraperitoneal IOX2. In vitro, human nasal chondrocytes and jawbone-derived bone marrow mesenchymal stem cells (BMSCs) were treated with IOX2 to assess chondrogenic/osteogenic differentiation via scratch assays, qPCR, Western blotting, and Alizarin Red/ALP staining. PHD2 expression peaked at postoperative day 14 (POD14) in osteocytes, correlating with osteoblast activation but minimal chondrogenic changes. IOX2 administration impaired fracture healing in vivo, reducing trabecular bone volume and delaying mineralization while increasing cartilaginous tissue retention. In vitro, IOX2 enhanced chondrocyte proliferation, proteoglycan deposition, and COL2A1/SOX9 expression but suppressed BMSC osteogenesis. PHD2 critically regulates condylar fracture repair by modulating PDGF-BB-driven crosstalk between osteocytes and chondrocytes. These findings identify PHD2-PDGF-BB signaling as a therapeutic target to optimize bone regeneration and functional recovery in condylar fractures.