BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization.

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2024-11-19 DOI:10.1186/s10020-024-00904-w

Yanbin Zhang, Jing Bai, Bin Xiao, Chunyan Li

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引用次数: 0

Abstract

Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exosomes in osteogenic differentiation and their potential therapeutic effects on osteoporosis. Exosomes were extracted from BMSCs. Bone marrow-derived macrophages (BMDMs) were cultured and internalized with BMSCs-derived exosomes. Real-time quantitative PCR was used to detect the expression of macrophage surface markers and tripartite motif (TRIM) family genes. BMDMs were co-cultured with human osteoblasts to assess osteogenic differentiation. Western blot was performed to analyze the ubiquitination of triggering receptor expressed on myeloid cell 1 (TREM1) mediated by TRIM25. An ovariectomized mice model was established to evaluate the role of TRIM25 and exosomes in osteoporosis. Exosomes were successfully isolated from BMSCs. BMSCs-derived exosomes upregulated TRIM25 expression, promoting M2 macrophage polarization and osteogenic differentiation. TRIM25 facilitated the ubiquitination and degradation of TREM1. Overexpression of TREM1 reversed the enhanced M2 macrophage polarization and osteogenic differentiation caused by TRIM25 overexpression. TRIM25 enhanced the protective effect of BMSCs-derived exosomes against bone loss in mice. These findings suggested that BMSCs-derived exosomes promoted osteogenic differentiation by regulating M2 macrophage polarization through TRIM25-mediated ubiquitination and degradation of TREM1. This mechanism might provide a novel approach for treating osteoporosis.

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BMSC衍生的外泌体通过M2巨噬细胞极化促进骨质疏松症的缓解

骨质疏松症的特点是骨代谢失衡导致骨量减少。从骨间充质干细胞（BMSCs）中提取的外泌体已被证明在多种疾病中发挥作用。本研究旨在阐明骨间充质干细胞衍生的外泌体在成骨分化过程中的调控功能和分子机制及其对骨质疏松症的潜在治疗作用。研究人员从 BMSCs 中提取了外泌体。培养骨髓源性巨噬细胞（BMDMs）并使其内化BMSCs衍生的外泌体。采用实时定量 PCR 检测巨噬细胞表面标记和三方基序（TRIM）家族基因的表达。BMDMs 与人类成骨细胞共同培养，以评估成骨分化。用 Western 印迹法分析 TRIM25 介导的髓细胞 1（TREM1）触发受体泛素化。为了评估TRIM25和外泌体在骨质疏松症中的作用，研究人员建立了卵巢切除小鼠模型。外泌体成功地从BMSCs中分离出来。BMSCs衍生的外泌体可上调TRIM25的表达，促进M2巨噬细胞极化和成骨分化。TRIM25促进了TREM1的泛素化和降解。TREM1的过表达逆转了TRIM25过表达引起的M2巨噬细胞极化和成骨分化的增强。TRIM25增强了BMSCs衍生的外泌体对小鼠骨质流失的保护作用。这些发现表明，BMSCs衍生的外泌体通过TRIM25介导的TREM1泛素化和降解，调节M2巨噬细胞极化，从而促进成骨分化。这一机制可能为治疗骨质疏松症提供了一种新方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.