Department of Research, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA.
Sci Rep. 2012;2:650. doi: 10.1038/srep00650. Epub 2012 Sep 11.
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.
青少年股骨头坏死是由于血液供应中断导致缺血性损伤。血管生成是受损头部愈合的必要组成部分。缺氧诱导因子-1α（HIF-1α）是细胞对缺氧反应的主要调节因子。我们的组织学研究表明，在猪股骨头坏死模型中，与对照组相比，缺血组软骨中的血管形成增加。微阵列和 RT-PCR 表明，VEGF 表达与 HIF-1α 在缺血侧一起上调。免疫组织化学检测表明，缺血性股骨头中的软骨细胞中 HIF-1α 和 VEGF 上调。在低氧状态下，原代软骨细胞中的 HIF-1α 和 VEGF 表达均增加。有趣的是，HIF-1α 激活剂 DFO 进一步增强了 VEGF 的表达。此外，针对 HIF-1α 的 siRNA 转染导致 VEGF 表达受到抑制。总之，我们的数据表明，软骨细胞在低氧环境下 VEGF 的上调部分是通过 HIF-1α 介导的。
