Receptor Activator of Nuclear Factor Kappa-B-Expressing Mesenchymal Stem Cells-Derived Extracellular Vesicles for Osteoporosis Therapy
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.
Authors
- Wenju Chang (ORCID: https://orcid.org/0000-0003-1182-4083)
- Jinyu Bai
- Qirong Dong (ORCID: https://orcid.org/0000-0001-6833-1576)
- Bingbing Wu (ORCID: https://orcid.org/0000-0001-9269-4414)
- Huajian Shan (ORCID: https://orcid.org/0009-0003-6903-7178)
- Xiaozhong Zhou (ORCID: https://orcid.org/0000-0002-2202-7699)
- Yue Zhang (ORCID: https://orcid.org/0000-0002-6612-8002)
- Chao Wang (ORCID: https://orcid.org/0000-0002-8054-3472)
- Qin Qin (ORCID: https://orcid.org/0000-0002-6432-2944)
- Dongxiao Li (ORCID: https://orcid.org/0000-0002-1996-143X)
- Mingchao Zhang (ORCID: https://orcid.org/0000-0001-8915-0459)
- Bo Tian (ORCID: https://orcid.org/0000-0002-8936-6783)
- Chenmeng Zhou (ORCID: https://orcid.org/0009-0004-2979-4091)
- Yichao Ni
Institutions
- Bengbu Medical College (CN)
- Soochow University (CN)
- Institute of Molecular Functional Materials (CN)
- Second Affiliated Hospital of Soochow University (CN)
- First Affiliated Hospital of Bengbu Medical College (CN)
Publication Details
- Journal
- ACS Nano
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1021/acsnano.4c12064
- Citations
- 11
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Jiangsu Province
- Anhui Provincial Department of Education
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Higher Education Discipline Innovation Project
- Graduate Research and Innovation Projects of Jiangsu Province
- National Key Research and Development Program of China