title: Regulation of VEGF expression by HIF-1α in the femoral head cartilage following ischemia osteonecrosis.
abstract: 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.
authors.affiliation: Department of Research, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA. Chi5.Zhang@utsouthwestern.edu
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Reuel
authors.initials: R
authors.lastname: Cornelia
authors.forename: Susanne
authors.initials: S
authors.lastname: Swisher
authors.forename: Harry
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D005270:Femur Head / Q000098:blood supply / Q000473:pathology; D005271:Femur Head Necrosis / Q000401:mortality*; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism; D018919:Neovascularization, Physiologic; D034421:Sus scrofa; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A