Pro-angiognetic and pro-osteogenic effects of human umbilical cord mesenchymal stem cell-derived exosomal miR-21-5p in osteonecrosis of the femoral head

被引:22
|
作者
Fang, Shanhong [1 ]
Liu, Zhaoliang [2 ]
Wu, Songye [3 ]
Chen, Xinjie [3 ]
You, Mengqiang [3 ]
Li, Yongfeng [3 ]
Yang, Fuhui [3 ]
Zhang, Shuhuan [3 ]
Lai, Yiqun [3 ]
Liu, Peiyao [3 ]
Jiang, Weijiawen [3 ]
Chen, Peng [1 ]
机构
[1] Fujian Med Univ, Fujian Orthopaed Res Inst, Dept Orthopaed, Affiliated Hosp 1, Fuzhou 350005, Peoples R China
[2] Fujian Med Univ, Res Inst Plast & Aesthet Surg, Dept Plast Surg, Affiliated Hosp 1, Fuzhou 350005, Peoples R China
[3] Fujian Med Univ, Fuzhou 350122, Peoples R China
关键词
GLUCOCORTICOID-INDUCED OSTEONECROSIS; EXTRACELLULAR VESICLES; SOX5; DIFFERENTIATION; ANGIOGENESIS; REGENERATION; EXPRESSION;
D O I
10.1038/s41420-022-00971-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mesenchymal stem cell (MSC)-derived exosomes (Exos) enhanced new bone formation, coupled with positive effects on osteogenesis and angiogenesis. This study aims to define the role of microRNA (miR)-21-5p delivered by human umbilical MSC-derived Exos (hucMSC-Exos) in the osteonecrosis of the femoral head (ONFH). We first validated that miR-21-5p expression was downregulated in the cartilage tissues of ONFH patients. Besides, hucMSCs delivered miR-21-5p to hFOB1.19 cells and human umbilical vein endothelial cells (HUVECs) through the secreted Exos. Loss- and gain-of-function approaches were performed to clarify the effects of Exo-miR-21-5p, SOX5, and EZH2 on HUVEC angiogenesis and hFOB1.19 cell osteogenesis. It was established that Exo-miR-21-5p augments HUVEC angiogenesis and hFOB1.19 cell osteogenesis in vitro, as reflected by elevated alkaline phosphatase (ALP) activity and calcium deposition, and increased the expression of osteogenesis-related markers OCN, Runx2 and Collagen I. Mechanistically, miR-21-5p targeted SOX5 and negatively regulated its expression, while SOX5 subsequently promoted the transcription of EZH2. Ectopically expressed SOX5 or EZH2 could counterweigh the effect of Exo-miR-21-5p. Further, hucMSC-Exos containing miR-21-5p repressed the expression of SOX5 and EZH2 and augmented angiogenesis and osteogenesis in vivo. Altogether, our study uncovered the role of miR-21-5p shuttled by hucMSC-Exos, in promoting angiogenesis and osteogenesis, which may be a potential therapeutic target for ONFH.
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页数:11
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