Changes in Hif-1α/ VEGF signal axis and type-H vessels in steroid-induced osteonecrosis of the femoral head
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1. Gansu University of Chinese Medicine, Lanzhou 730000, China. 2. Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000. 3. Chengdu University of Chinese Medicine, Chengdu 610000. 4. Baoji Hospital of Chinese Medicine, Baoji 721000

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    Abstract:

    Objective To observe the changes in the hypoxia-inducible factor 1α (Hif-1α) / vascular endothelial growth factor (VEGF) signaling axis and specific type H vessels in the femoral head of steroid-induced osteonecrosis of the femoral head ( SONFH) model rats and explore the role of these changes in the development of osteonecrosis. Methods Thirty specific pathogen-free grade male Sprague-Dawley rats were randomly divided into a control group ( CG), model group ( MG) and deferoxamine group ( DFOG), with 10 rats in each group. The MG and DFOG were treated with methylprednisolone combined with lipopolysaccharide for SONFH modeling, the CG and MG received intraperitoneal injections of normal saline, and the DFOG received intraperitoneal injections of 250 mg / kg deferoxamine mesylate. Six weeks after modeling, micro-computed tomography was performed to observe the microstructural changes of the femoral head, hematoxylin / eosin staining was used to observe the histopathological changes of the femoral head, immunofluorescence staining was used to analyze the changes of type H vessels in the femoral head, and reverse- transcription polymerase chain reaction (RT-PCR) was used to analyze expression of HIF-1α/ VEGF signaling axis-related factors in the femoral head. Results Micro-computed tomography analysis showed that the femoral head in the MG and DFOG had sparse bone trabeculae, but the bone trabeculae in the MG exhibited fractures and the femoral head showed subchondral cystic degeneration. Hematoxylin / eosin staining showed that compared with the CG, both the MG and DFOG had obvious femoral head necrosis (P< 0. 01). Immunofluorescence staining showed that compared with the CG, the amount of type H vessels in the femoral head was significantly lower in the MG (P< 0. 05) and significantly higher in the DFOG (P< 0. 01). Compared with the CG, the amount of Osterix+ osteoblast (progenitor) cells was significantly lower in the MG (P< 0. 01) and significantly higher in the DFOG (P< 0. 01). RT-PCR showed that the expression of HIF-1α, VEGF, osterix, and Runx2 (mRNA) in the femoral head was significantly lower in the MG than CG (P< 0. 01) and significantly higher in the DFOG than MG ( P< 0. 01). Conclusions Steroid-induced HIF-1α/ VEGF signaling axis dysregulation and specific type H vessel damage were observed in this SONFH rat model, suggesting that bone-specific type H vessel damage may be a key pathogenetic factor of SONFH.

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  • Received:March 06,2022
  • Revised:
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  • Online: January 19,2023
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