Receptor Activator of Nuclear Factor Kappa-B-Expressing Mesenchymal Stem Cells-Derived Extracellular Vesicles for Osteoporosis Therapy

IF 15.8 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Nano Pub Date : 2024-12-18 DOI:10.1021/acsnano.4c12064

Wenju Chang, Bo Tian, Qin Qin, Dongxiao Li, Yue Zhang, Chenmeng Zhou, Bingbing Wu, Mingchao Zhang, Huajian Shan, Yichao Ni, Qirong Dong, Chao Wang, Xiao-Zhong Zhou, Jinyu Bai

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Abstract

The dynamic balance between bone resorption and formation is critical for maintaining healthy bone homeostasis. However, the receptor activator of the nuclear factor B ligand (RANKL) primarily stimulates mature osteoclasts to resorb bone, and its upregulation leads to osteoporosis in patients. Here, we designed RANK-expressing extracellular vesicles (EVs) derived from mesenchymal stem cells to maintain bone homeostasis in mice. This engineered EV (EV@R) effectively neutralizes excess RANKL in bone tissue due to the RANK–RANKL interaction, thereby attenuating osteoclast differentiation. Additionally, we found that miRNA-21a-5p in EV@R contributes to restoring bone metabolic homeostasis. We demonstrate the protective and therapeutic efficacy of EV@R against osteoporosis in the ovariectomy-induced osteoporosis mouse model with a lasting effect and minimal side effects. Our study provides an alternative way to use engineered EVs for bone homeostasis treatment.

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表达核因子 Kappa-B 受体活化剂的间充质干细胞衍生的细胞外囊泡用于骨质疏松症治疗

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来源期刊

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.