| Autor: |
Shanhong Fang, Zhaoliang Liu, Songye Wu, Xinjie Chen, Mengqiang You, Yongfeng Li, Fuhui Yang, Shuhuan Zhang, Yiqun Lai, Peiyao Liu, Weijiawen Jiang, Peng Chen |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cell Death Discovery, Vol 8, Iss 1, Pp 1-11 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2058-7716 |
| DOI: |
10.1038/s41420-022-00971-0 |
| Popis: |
Abstract 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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