Desferoxamine protects against glucocorticoid-induced osteonecrosis of the femoral head via activating HIF-1α expression
Desferoxamine protects against glucocorticoid-induced osteonecrosis of the femoral head via activating HIF-1α expression
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DOI：
10.1002/jcp.29799
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发表时间：
2020-05-21
影响因子：
5.6
通讯作者：
Jiang, Zhensong
中科院分区：
文献类型：
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作者：
Jing, Xingzhi;Du, Ting;Jiang, Zhensong
糖皮质激素引起的股骨头坏死（GIOFH）是糖皮质激素给药最常见的并发症之一。据报道，通过螯合 Fe2+，去铁胺 (DFO) 能够激活 HIF-1 α/VEGF 通路并促进血管生成。在本研究中，我们检查了 DFO 给药是否可以促进 GIOFH 的血管生成和骨修复。甲泼尼龙与脂多糖联合诱导大鼠发生 GIOFH。通过组织学分析和显微计算机断层扫描（micro-CT）评估骨修复。通过 Microfil 灌注和 micro-CT 分析评估血管化。进行免疫组织化学染色来分析HIF-1α、VEGF和CD31的表达。我们的体内研究表明，DFO 增加了 GIOFH 中 HIF-1 α/VEGF 的表达并促进了血管生成和成骨。此外，我们的体外研究表明，DFO 可以恢复地塞米酮诱导的 HIF-1 α 下调和血管生成抑制。此外，我们的体外研究还表明，DFO 可以通过促进线粒体自噬和线粒体裂变，保护骨髓干细胞免受地塞米酮诱导的细胞凋亡和线粒体功能障碍。总之，我们的数据为开发治疗 GIOFH 的新疗法提供了有用的信息。
Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is one of the most common complications of glucocorticoid administration. By chelating Fe2+, desferoxamine (DFO) was reported to be able to activate the HIF-1 alpha/VEGF pathway and promote angiogenesis. In the present study, we examined whether DFO administration could promote angiogenesis and bone repair in GIOFH. GIOFH was induced in rats by methylprednisolone in combination with lipopolysaccharide. Bone repair was assessed by histologic analysis and microcomputed tomography (micro-CT). Vascularization was assessed by Microfil perfusion and micro-CT analysis. Immunohistochemical staining was performed to analyze the expression of HIF-1 alpha, VEGF, and CD31. Our in vivo study revealed that DFO increased HIF-1 alpha/VEGF expression and promoted angiogenesis and osteogenesis in GIOFH. Moreover, our in vitro study revealed that DFO restored dexamethone-induced HIF-1 alpha downregulation and angiogenesis inhibition. Besides, our in vitro study also demonstrated that DFO could protect bone marrow-derived stem cells from dexamethone-induced apoptosis and mitochondrial dysfunction by promoting mitophagy and mitochondrial fission. In summary, our data provided useful information for the development of novel therapeutics for management of GIOFH.