α2-macroglobulin alleviates glucocorticoid-induced avascular necrosis of the femoral head in mice by promoting proliferation, migration and angiogenesis of vascular endothelial cells
10.12122/j.issn.1673-4254.2024.04.13
- VernacularTitle:α2-巨球蛋白通过调控血管内皮细胞改善小鼠激素性股骨头坏死
- Author:
Qi ZHU
1
;
Yunxiang LU
;
You PENG
;
Jiale HE
;
Zeyu WEI
;
Zhiyong LI
;
Yuxian CHEN
Author Information
1. 中山大学附属第三医院关节外科创伤骨科,广东 广州 510630
- Keywords:
α2-macroglobulin;
steroid-induced avascular necrosis of the femoral head;
endothelial dysfunction;
vascular endothelial growth factor-A
- From:
Journal of Southern Medical University
2024;44(4):712-719
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.
