Abstract
Background/aim:
To investigate the role of epidermal growth factor receptor (EGFR) inhibition in enhancing bone fracture healing by modulating box transcription factor 9 (SOX9) and bone metabolism.
Materials and methods:
A rat femoral fracture model was used. Techniques included histological analysis, X-ray scoring, micro-computed tomography, immunohistochemistry, and biomechanical testing. Serum markers were analyzed with enzyme-linked immunosorbent assay, while quantitative real-time polymerase chain reaction and western blotting assessed molecular pathways. Metabolic changes were measured using a Seahorse analyzer. An EGFR inhibitor, gefitinib, was used to examine its impact on periosteal stem cell differentiation and metabolism.
Results:
EGFR inhibition improved bone callus formation and quality, increased cartilage callus, and upregulated bone formation markers. Gefitinib enhanced oxidative phosphorylation and fatty acid oxidation, counteracting negative effects from lipid-reduced serum on osteoblastic differentiation of periosteal stem cell. SOX9 overexpression reduced the benefits of EGFR inhibition.
Conclusion:
Gefitinib enhances bone fracture healing by modulating lipid metabolism through SOX9, suggesting its potential as a therapeutic agent for improving fracture outcomes.
Keywords:
Bone metabolism; EGFR; SOX9; SRY-box transcription factor 9; epidermal growth factor receptor; fracture healing; gefitinib.