The Proosteogenic and Proangiogenic Effects of Small Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Are Attenuated in Steroid-Induced Osteonecrosis of the Femoral Head

被引:15
作者
Li, Jia [1 ]
Ge, Zhaogang [2 ]
Ji, Wenchen [1 ]
Yuan, Na [3 ]
Wang, Kunzheng [4 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Orthoped, Xian 710061, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Honghui Hosp, Dept Joint Surg, Xian 710054, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Ultrasonog, Xian 710061, Shaanxi, Peoples R China
[4] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Orthoped 1, Xian 710004, Shaanxi, Peoples R China
关键词
PPAR-GAMMA; EXOSOMES; ANGIOGENESIS; DIFFERENTIATION; MICROVESICLES; OSTEOGENESIS; APOPTOSIS; RATS;
D O I
10.1155/2020/4176926
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Small extracellular vesicles (sEVs) derived from bone marrow mesenchymal stem cells (BMMSCs) from individuals with steroid-induced osteonecrosis of the femoral head (ONFH) have not been studied. The objective of the present study was to compare the proosteogenic and proangiogenic effects of sEVs derived from BMMSCs from rats with steroid-induced ONFH (oBMMSCs-sEVs) and sEVs derived from BMMSCs from normal rats (nBMMSCs-sEVs). BMMSCs were isolated from steroid-induced ONFH rats and healthy rats. sEVs were isolated and characterized by Western blotting analysis of exosomal surface biomarkers and by transmission electron microscopy. The impacts of nBMMSCs-sEVs and oBMMSCs-sEVs on the proliferation and osteogenic differentiation of BMMSCs were determined via cell proliferation assay, alizarin red staining, and alkaline phosphatase activity assay. Enzyme-linked immunosorbent assay and tube formation assay were conducted to investigate the effect of nBMMSCs-sEVs and oBMMSCs-sEVs on the angiogenic potential of human umbilical vein endothelial cells (HUVECs). The expression of relevant genes was detected by quantitative real-time polymerase chain reaction analysis, and the expression of beta-catenin was detected by immunofluorescence. Both nBMMSCs-sEVs and oBMMSCs-sEVs promoted proliferation, osteogenic differentiation, and beta-catenin expression of BMMSCs and enhanced angiogenesis of HUVECs. However, compared with nBMMSCs-sEVs, oBMMSCs-sEVs exhibited attenuated effects. Our findings indicated that the proosteogenic and proangiogenic effects of sEVs were partially attenuated in steroid-induced ONFH. Therefore, this study might offer guidance for the selection of source cells for sEV therapy in the future.
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页数:11
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