Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is one of the most common complications of glucocorticoid administration. By chelating Fe , 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.
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Article Synopsis
- Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) leads to bone damage and hip dysfunction, with sclerostin playing a key role in bone health and breakdown.
- The study used various cell models and animal models to examine how sclerostin affects bone cells under glucocorticoid treatment.
- Results showed that high levels of sclerostin contribute to the progression of GA-ONFH by hindering bone growth and blood vessel formation, highlighting its potential as a target for treatment.
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