Icariin-Enhanced Osteoclast-Derived Exosomes Promote Repair of Infected Bone Defects by Regulating Osteoclast and Osteoblast Communication.

IF 6.6 2区医学 Q1 NANOSCIENCE & NANOTECHNOLOGY

International Journal of Nanomedicine Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S483621

Yang Zhang, Minjie Zhang, Mengying Li, Maomao Miao, Dan Shou, Peijian Tong

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引用次数: 0

Abstract

Background: Infected bone defects pose a challenging clinical issue due to an imbalance of osteoclasts (OC) and osteoblasts (OB). Exosomes are crucial for intercellular signaling of OC and OB in bone repair. Icariin, has been shown to regulate the balance between OC and OB. However, the specific mechanisms by which icariin influences exosomes derived from osteoclasts, and subsequently impacts osteoblast activity, remain unclear. This study aims to investigate the effects of icariin-treated osteoclast-derived exosomes (ICA-OC-Exo) on osteoblast function and bone repair in cases of infected bone defects.

Methods: We investigated the exosome profile and localization of multivesicular bodies (MVB) and quantification of intraluminal vesicles (ILVs) in osteoclasts by using transmission electron microscopy. Additionally, the expressions of Rab27A and MITF, which are associated with exosome release, were determined through immunofluorescence staining and Western blot. The profiling of exosomal miRNA expression was conducted via miRNA-sequencing. The effects of ICA-OC-Exo on osteoblast differentiation were determined using RT-qPCR, Western blot, alkaline phosphatase staining. Additionally, ICA-OC-Exo was administered into the localized bone defect of the infected bone rat models, and bone formation was assessed using Micro-CT.

Results: Icariin increased the presence of MVBs in the cytoplasm through modulation of the MITF/Rab27A signaling pathway, resulting in higher number of ICA-OC-Exo compared to OC-Exo. Additionally, miR-331-3p expression in ICA-OC-Exo was found to be elevated compared to OC-Exo. ICA-OC-Exo was observed to stimulate osteoblast function by targeting FGF23, reducing DKK1, and subsequently upregulating ALP. In the in vivo study, ICA-OC-Exo exhibited the capacity to enhance bone healing at the site of a local bone defect following anti-infection treatment.

Conclusion: Icariin enhanced the quantification of OC-Exo and the expression of miRNA-331-3p in OC-Exo, leading to the regulation of osteoblast function via activation of the miRNA-331-3p/FGF23/DKK1 pathway. ICA-OC-Exo demonstrated potential clinical applicability in bone repair of infected bone defects.

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淫羊藿苷增强的破骨细胞衍生外泌体通过调控破骨细胞和成骨细胞的交流促进感染性骨缺损的修复

背景：由于破骨细胞（OC）和成骨细胞（OB）的不平衡，感染性骨缺损是一个具有挑战性的临床问题。外泌体是骨修复中破骨细胞和成骨细胞细胞间信号传递的关键。研究表明，淫羊藿苷可以调节破骨细胞和成骨细胞之间的平衡。然而，伊卡丽素影响破骨细胞产生的外泌体并进而影响成骨细胞活性的具体机制仍不清楚。本研究旨在探讨经冰片素处理的破骨细胞衍生外泌体（ICA-OC-Exo）对感染性骨缺损病例中成骨细胞功能和骨修复的影响：我们利用透射电子显微镜研究了破骨细胞中外泌体的特征、多泡体（MVB）的定位以及腔内囊泡（ILV）的定量。此外，还通过免疫荧光染色和 Western 印迹测定了与外泌体释放相关的 Rab27A 和 MITF 的表达。通过 miRNA 测序分析了外泌体 miRNA 的表达。利用 RT-qPCR、Western 印迹和碱性磷酸酶染色确定了 ICA-OC-Exo 对外骨细胞分化的影响。此外，还在感染骨大鼠模型的局部骨缺损处注射了ICA-OC-Exo，并使用Micro-CT评估了骨形成情况：结果：淫羊藿苷通过调节MITF/Rab27A信号通路增加了细胞质中MVB的存在，导致ICA-OC-Exo的数量高于OC-Exo。此外，与 OC-Exo 相比，ICA-OC-Exo 中 miR-331-3p 的表达也有所升高。据观察，ICA-OC-Exo 可通过靶向 FGF23、减少 DKK1 和随后上调 ALP 来刺激成骨细胞功能。在体内研究中，ICA-OC-Exo表现出了在抗感染治疗后促进局部骨缺损部位骨愈合的能力：结论：淫羊藿苷提高了OC-Exo的定量和OC-Exo中miRNA-331-3p的表达，从而通过激活miRNA-331-3p/FGF23/DKK1途径调节成骨细胞功能。ICA-OC-Exo在感染性骨缺损的骨修复方面具有潜在的临床应用价值。

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来源期刊

International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

14.40

自引率

3.80%

发文量

511

审稿时长

1.4 months

期刊介绍： The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.