Endothelial Cell-Derived Exosomes Inhibit Osteoblast Apoptosis and Steroid-Induced Necrosis of Femoral Head Progression by Activating the PI3K/Akt/Bcl-2 Pathway

The aim of the study was to investigate the therapeutic potential of exosomes secreted by endothelial cells (EC-exos) on steroid-induced osteonecrosis of femoral head (SNFH). First, we successfully obtained EC-exos through differential centrifugation. Then, the effects of EC-exos on mouse embryo ost...

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Published in:Journal of tissue engineering and regenerative medicine 2024-05, Vol.2024, p.1-11
Main Authors: Sun, Jie, Yao, Chen, Luo, Wanxin, Ge, Xingyu, Zheng, Wenjie, Sun, Chi, Zhang, Yafeng
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Antibodies
Apoptosis
Bcl-2 protein
Cell growth
Cell migration
Cell viability
Centrifugation
Computed tomography
Dexamethasone
Disease
Endothelial cells
Exosomes
Femur
Flow cytometry
Kinases
Laboratory animals
Microscopy
Necrosis
Osteoblasts
Osteocytes
Osteonecrosis
Proteins
Signal transduction
Steroids
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Summary:The aim of the study was to investigate the therapeutic potential of exosomes secreted by endothelial cells (EC-exos) on steroid-induced osteonecrosis of femoral head (SNFH). First, we successfully obtained EC-exos through differential centrifugation. Then, the effects of EC-exos on mouse embryo osteoblast precursor (MC3T3-E1) cells under high concentration of dexamethasone (Dex) were analysed in vitro, which included cell migration, viability, and apoptosis. In vivo, a SNFH rat model was successfully established and treated with EC-exos. Micro-computed tomography (micro-CT) and haematoxylin and eosin (H&E) were used to observe femoral trabeculae. Our in vitro results showed that EC-exos improved cell viability and migration of osteoblasts and reduced the apoptotic effect of high concentration of Dex on osteoblasts in vitro. Phosphoinositide 3-kinase (PI3K)/Akt/Bcl-2 signalling pathway was activated in MC3T3-E1 cells under the response to EC-exos. In vivo, increased bone volume per tissue volume (BV/TV) p=0.031, trabecular thickness (Tb.Th) p=0.020, and decreased separation (Tb.Sp) p=0.040 were observed in SNFH rats treated with EC-exos. H&E staining revealed fewer empty lacunae and pyknotic osteocytes in trabeculae. The expression of Bcl-2 and Akt in EC-exos group was significantly increased in trabeculae tissue. Overall, our finding indicated that EC-exos could attenuate SNFH by inhibiting osteoblast apoptosis via the PI3K/Akt/Bcl-2 pathway.
ISSN:1932-6254
1932-7005
DOI:10.1155/2024/3870988