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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container_title Journal of tissue engineering and regenerative medicine
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creator Sun, Jie
Yao, Chen
Luo, Wanxin
Ge, Xingyu
Zheng, Wenjie
Sun, Chi
Zhang, Yafeng
description 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.
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H&amp;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. 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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
title Endothelial Cell-Derived Exosomes Inhibit Osteoblast Apoptosis and Steroid-Induced Necrosis of Femoral Head Progression by Activating the PI3K/Akt/Bcl-2 Pathway
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