IF 2.7 4区 生物学 Q1 ANATOMY & MORPHOLOGY Tissue & cell Pub Date : 2024-11-30 DOI:10.1016/j.tice.2024.102645
Zi-Yan Guo, Nan-Nan Yin, Xiao-Fei Li, Meng-Meng Wang, Xiao-Na Sui, Cai-di Jiang, Ming-Hua Xu, Xiao-E Jia, Chong-Jian Fu, Tie-Lou Chen, Xin Liu
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引用次数: 0

摘要

目的:由破骨细胞分化介导的骨吸收会诱发骨相关疾病。巨噬细胞是破骨细胞的起源之一,其 M2 型可减少炎症引起的骨损伤。我们旨在研究 M2 型巨噬细胞衍生的外泌体对破骨细胞形成的影响,并阐明其潜在机制:从 M2 巨噬细胞(M2-exo)中分离出外泌体,用于处理破骨细胞样细胞。使用耐酒石酸磷酸酶、实时定量聚合酶链反应(qRT-PCR)和 Western 印迹法评估破骨细胞的形成。通过qRT-PCR、磷酸激酶阵列分析和Western印迹分析了M2-exo功能的分子机制:结果:M2-exo可被破骨细胞内化,并抑制破骨细胞的体外分化。此外,CYLD在M2巨噬细胞和经M2-exo处理的破骨细胞中高表达,敲除CYLD可减轻M2-exo对破骨细胞分化的抑制作用。此外,CYLD抑制了STAT3的磷酸化,STAT3激活剂colivelin逆转了CYLD过表达对破骨细胞分化的抑制作用:结论:M2-exo通过传递CYLD抑制破骨细胞分化,而CYLD则使STAT3信号失活。结论:M2-exo 通过传递 CYLD 抑制破骨细胞分化,而 CYLD 可使 STAT3 信号失活。
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Exosomes secreted from M2-polarized macrophages inhibit osteoclast differentiation via CYLD.

Objective: Bone resorption mediated by osteoclast differentiation induces the occurrence of bone-related diseases. Macrophages, an origin of osteoclasts, whose M2 type can reduce inflammation-induced bone damage. We aimed to investigate the effect of M2 macrophage-derived exosomes on osteoclast formation and elucidate its underlying mechanism.

Materials and methods: Exosomes were isolated from M2 macrophages (M2-exo) and were used to treat osteoclast-like cells. Osteoclast formation was evaluated using tartrate-resistant acid phosphatase, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. The molecular mechanism of M2-exo function was analyzed by qRT-PCR, phosphor-kinase array analysis, and Western blotting.

Results: M2-exo was internalized by osteoclasts and inhibited osteoclast differentiation in vitro. Moreover, CYLD was highly expressed in M2 macrophages and M2-exo-treated osteoclasts, and knockdown of it abrogated the inhibition of osteoclast differentiation caused by M2-exo. Additionally, CYLD suppressed the phosphorylation of STAT3, and STAT3 activator colivelin reversed the inhibition of osteoclast differentiation induced by CYLD overexpression.

Conclusion: M2-exo inhibits osteoclast differentiation via delivering CYLD, which inactivates STAT3 signaling. These findings may provide a novel therapeutic option for bone diseases including periodontitis.

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来源期刊
Tissue & cell
Tissue & cell 医学-解剖学与形态学
CiteScore
3.90
自引率
0.00%
发文量
234
期刊介绍: Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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