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M1 macrophage‐derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA‐98/DUSP1/JNK axis
- 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.
- Subjects :
- MAP Kinase Signaling System
Osteoporosis
Down-Regulation
Exosomes
Cell Line
Mice
Immune system
Downregulation and upregulation
Osteogenesis
microRNA
Dual-specificity phosphatase
medicine
Animals
Humans
Macrophage
Osteoporosis, Postmenopausal
Osteoblasts
biology
Chemistry
Macrophages
Cell Differentiation
Dual Specificity Phosphatase 1
3T3 Cells
Cell Biology
General Medicine
medicine.disease
Microvesicles
Up-Regulation
Mice, Inbred C57BL
Disease Models, Animal
MicroRNAs
RAW 264.7 Cells
Cancer research
biology.protein
Phosphorylation
Female
Subjects
Details
- ISSN :
- 10958355 and 10656995
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Cell Biology International
- Accession number :
- edsair.doi.dedup.....1aac91d9a577841298e0959f76f23aad