Desferoxamine protects against glucocorticoid‐induced osteonecrosis of the femoral head via activating HIF‐1α expression

• Published in: Journal of cellular physiology 2020-12, Vol.235 (12), p.9864-9875
• Main Authors: Jing, Xingzhi, Du, Ting, Yang, Xiaoxia, Zhang, Weimin, Wang, Guodong, Liu, Xiaoyang, Li, Tao, Jiang, Zhensong
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Apoptosis; Biomedical materials; Bone healing; Bone marrow; Bone Regeneration - drug effects; Chelation; Computed tomography; Deferoxamine; Deferoxamine - pharmacology; desferoxamine; Drug development; Femur; Femur Head - drug effects; Femur Head - growth & development; Gene Expression Regulation - drug effects; Glucocorticoids; Glucocorticoids - toxicity; HIF‐1α; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; In vivo methods and tests; Iron; Lipopolysaccharides; Methylprednisolone; Mitochondria; mitophagy; Neovascularization, Physiologic - drug effects; Osteogenesis; Osteogenesis - drug effects; Osteonecrosis; Osteonecrosis - chemically induced; Osteonecrosis - drug therapy; Osteonecrosis - pathology; osteonecrosis of the femoral head; Perfusion; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Rats; Repair; Stem cell transplantation; Stem cells; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascularization; X-Ray Microtomography
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29799

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‐1α/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‐1α, VEGF, and CD31. Our in vivo study revealed that DFO increased HIF‐1α/VEGF expression and promoted angiogenesis and osteogenesis in GIOFH. Moreover, our in vitro study revealed that DFO restored dexamethone‐induced HIF‐1α 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. By chelating Fe2+, desferoxamine (DFO) was reported to be able to activate the HIF‐1α/VEGF pathway and promote angiogenesis. In the present study, we demonstrated that DFO administration could promote angiogenesis and bone repair in glucocorticoid‐induced osteonecrosis of the femoral head.