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M1 macrophage‐derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA‐98/DUSP1/JNK axis

Authors :
Long Yu
Da Bao
Xiao-Bo Luo
Yunfeng Wu
Yuan-Zheng Ma
Ming Hu
Xu Cui
Li Litao
Liu Ning
Dawei Li
Zhanpeng Luo
Source :
Cell Biology International. 45:2452-2463
Publication Year :
2021
Publisher :
Wiley, 2021.

Abstract

Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ-exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)-98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX-treated mice, which presented a reduced bone mineral density and number of bone trabecula, and it was further aggravated by treatment with M1Mφ-Exos. Exos also suppressed osteogenic differentiation of MC3T3-E1 cells. miRNA microarray analysis revealed that miR-98 levels were notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR-98. Meanwhile, downregulation of miR-98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3-E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ-derived exosomal miR-98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR-98 may therefore serve as a therapeutic target in OP management. This article is protected by copyright. All rights reserved.

Details

ISSN :
10958355 and 10656995
Volume :
45
Database :
OpenAIRE
Journal :
Cell Biology International
Accession number :
edsair.doi.dedup.....1aac91d9a577841298e0959f76f23aad