Regulation of Vascular Endothelial Growth Factor (VEGF) Expression by Hypoxia-inducible Factor-1 in the Femoral Head Cartilage Following Ischemia Osteonecrosis

INTRODUCTOIN: Legg-Calve-Perthes disease (LCPD) is a common juvenile form of ischemic osteonecrosis of the femoral head that affects children between the ages of 2 to 14 years and has the attack rate of 1 in 740 boys and 1 in 3700 girls. LCPD is due to blood supply disruption to the femoral head. Ischemic osteonecrosis of the femoral head remains one of the most challenging conditions to treat due to the lack of understanding of the biology of the disease and our inability to modulate the repair process. Pig model of juvenile ischemic osteonecrosis of the femoral head has been shown to have radiographic and histopathologic changes resembling Legg-Calve-Perthes disease. In the model, the induction of total femoral head ischemia produced extensive cell death in the hypertrophy zone of the epiphyseal cartilage and produced growth arrest of the secondary center of ossification, the bony epiphysis. Angiogenesis is an essential component for the healing of damaged head. Hypoxia-inducible factor-1 α (HIF-1α) is a master regulator of cellular response to hypoxia. Our preliminary histological studies showed increased vessel formation in cartilage in the ischemic group compared to the control group in a pig model of femoral head osteonecrosis. The mechanism underlying this angiogenesis response to ischemic in the cartilage and its significance to the repair process is an interesting area of research that may provide new insights into how we can stimulate revascularization and repair following femoral head