Статья

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

Shanhong FangDepartment of Orthopaedics, Fujian Orthopaedics Research Institute, The First Affiliated Hospital of Fujian Medical University, 350005, Fuzhou, P. R. ChinaZhaoliang LiuDepartment of Plastic Surgery, Research Institute of Plastic and Aesthetic Surgery, The First Affiliated Hospital of Fujian Medical University, 350005, Fuzhou, P. R. ChinaSongye WuFujian Medical University, 350122, Fuzhou, P. R. ChinaXinjie ChenFujian Medical University, 350122, Fuzhou, P. R. ChinaMengqiang YouFujian Medical University, 350122, Fuzhou, P. R. ChinaYongfeng LiFujian Medical University, 350122, Fuzhou, P. R. ChinaFuhui YangFujian Medical University, 350122, Fuzhou, P. R. ChinaShuhuan ZhangFujian Medical University, 350122, Fuzhou, P. R. ChinaYiqun LaiFujian Medical University, 350122, Fuzhou, P. R. ChinaPeiyao LiuFujian Medical University, 350122, Fuzhou, P. R. ChinaWeijiawen JiangFujian Medical University, 350122, Fuzhou, P. R. ChinaPeng ChenDepartment of Orthopaedics, Fujian Orthopaedics Research Institute, The First Affiliated Hospital of Fujian Medical University, 350005, Fuzhou, P. R. China. [email protected]

2022en

ABI

Аннотация

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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Идентификаторы

DOI: 10.1038/s41420-022-00971-0

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar