M2 macrophages-derived exosomes for osteonecrosis of femoral head treatment: modulating neutrophil extracellular traps formation and endothelial phenotype transition

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING
Guanzhi Liu, Ruomu Cao, Qimeng Liu, Heng Li, Peng Yan, Kunzheng Wang, Run Tian, Pei Yang
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Abstract

Exosomes have shown good potential in ischemic injury disease treatments. However, evidence about their effect and molecular mechanisms in osteonecrosis of femoral head (ONFH) treatment is still limited. Here, we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes (M2-Exos). We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition. Additionally, we identified that M2-Exos’ therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adeno-associated virus respectively. Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells. These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.

Abstract Image

M2巨噬细胞衍生外泌体治疗股骨头坏死:调节中性粒细胞胞外陷阱形成和内皮表型转变
外泌体在缺血性损伤疾病的治疗中显示出良好的潜力。然而,关于它们在股骨头坏死(ONFH)治疗中的作用和分子机制的证据仍然有限。在这里,我们揭示了ONFH骨坏死区骨组织在单细胞尺度上的细胞生物学特性,从而确定了一种基于M2巨噬细胞来源的外泌体(M2- exos)的ONFH治疗新方法。我们进一步表明,M2-Exos通过调节中性粒细胞和内皮细胞之间的表型交流,包括中性粒细胞胞外陷阱的形成和内皮细胞表型的转变,在ONFH的治疗中非常有效。此外,我们发现M2-Exos的治疗效果归因于miR-93-5p的高含量,并分别基于慢病毒和腺相关病毒构建了miR-93-5p体外和体内过表达模型。我们发现miR-93-5p不仅可以减少中性粒细胞胞外陷阱的形成,还可以提高内皮细胞的血管生成能力。这些结果为ONFH治疗性外泌体的临床应用提供了新的理论依据。
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来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
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