Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
PLoS One. 2013 May 13;8(5):e63628. doi: 10.1371/journal.pone.0063628. Print 2013.
Although corticosteroid-induced osteonecrosis of the femoral head (ONFH) is common, the treatment for it remains limited and largely ineffective. We examined whether implantation of hypoxia inducible factor-1α (HIF-1α) transgenic bone marrow cells (BMCs) can promote the repair of the necrotic area of corticosteroid-induced ONFH. In this study, we confirmed that HIF-1α gene transfection could enhance mRNA expression of osteogenic genes in BMCs in vitro. Alkaline phosphatase activity assay and alizarin red-S staining indicated HIF-1α transgenic BMCs had enhanced osteogenic differentiation capacity in vitro. Furthermore, enzyme linked immunosorbent assay (ELISA) for VEGF revealed HIF-1α transgenic BMCs secreted more VEGF as compared to normal BMCs. An experimental rabbit model of early-stage corticosteroid-induced ONFH was established and used for an evaluation of cytotherapy. Transplantation of HIF-1α transgenic BMCs dramatically improved the bone regeneration of the necrotic area of the femoral head. The number and volume of blood vessel were significantly increased in the necrotic area of the femoral head compared to the control groups. These results support HIF-1α transgenic BMCs have enhanced osteogenic and angiogenic activity in vitro and in vivo. Transplantation of HIF-1α transgenic BMCs can potentially promote the repair of the necrotic area of corticosteroid-induced ONFH.
尽管激素诱导性股骨头坏死(ONFH)很常见,但治疗方法仍然有限且效果不佳。我们研究了缺氧诱导因子-1α(HIF-1α)转基因骨髓细胞(BMCs)的植入是否可以促进激素诱导性 ONFH 坏死区域的修复。在这项研究中,我们证实 HIF-1α 基因转染可以增强 BMCs 中成骨基因的 mRNA 表达。碱性磷酸酶活性测定和茜素红-S 染色表明 HIF-1α 转基因 BMCs 在体外具有增强的成骨分化能力。此外,血管内皮生长因子(VEGF)的酶联免疫吸附测定(ELISA)显示 HIF-1α 转基因 BMCs 分泌的 VEGF 比正常 BMCs 多。建立了早期激素诱导性 ONFH 的实验兔模型,并用于细胞治疗评估。HIF-1α 转基因 BMCs 的移植显著改善了股骨头坏死区域的骨再生。与对照组相比,坏死区域的血管数量和体积明显增加。这些结果支持 HIF-1α 转基因 BMCs 在体外和体内具有增强的成骨和成血管活性。HIF-1α 转基因 BMCs 的移植可能有助于促进激素诱导性 ONFH 坏死区域的修复。