Juvenile femoral head osteonecrosis is due to disruption of blood supply which results in ischemic injury. Angiogenesis is an essential component for the healing of damaged head. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator of cellular response to hypoxia. Our 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. Microarray and RT-PCR indicated that VEGF expression was upregulated along with HIF-1α in the ischemic side. Immunohistochemistry assay demonstrated that HIF-1α and VEGF were upregulated in chondrocytes in ischemic femoral heads. Both HIF-1α and VEGF expression increased in primary chondrocytes under hypoxia station. Interestingly, an HIF-1α activator DFO further enhanced VEGF expression. Moreover, transfection of siRNA directed against HIF-1α led to inhibition of VEGF expression. Taken together, our data indicated that upregulation of VEGF during hypoxia in chondrocyte is mediated partially through HIF-1α.

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