DataVXACS NanoPaper
journal article·2024-12-31

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

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

ACS Nano· Volume 18· Issue 52
Publisher page
Source abstract

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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · RNA Interference and Gene Delivery · MicroRNA in disease regulation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Orthopedics

The Second Affiliated Hospital of Soochow University

The First Affiliated Hospital of Bengbu Medical University

Anhui Province Key Laboratory of Tissue Transplantation (Bengbu Medical University)

Department of Obstetrics and Gynecology

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices

Soochow University

Funding

Jiangsu Provincial Department of Education · Collaborative Innovation Center of Suzhou Nano Science and Technology · Ministry of Science and Technology of the People's Republic of China · Natural Science Foundation of Jiangsu Province · Anhui Department of Education · National Natural Science Foundation of China · Higher Education Discipline Innovation Project · Jiangsu Provincial Medical Key Discipline · Nuclear Medicine Technology Innovation Project by China Nuclear Medical · Social Development Key Programs of Jiangsu Province-Advanced Clinical Technology · Gusu health talent plan-research project · Clinical Innovation and Interdisciplinary Translation Project of Suzhou Medical College, Soochow University · Gusu health talent plan-special talents C

References (48)

Show source-provided references
1. 10.1038/s41586-018-0482-710.1038/s41586-018-0482-7 ↗
2. 10.1172/jci14021410.1172/jci140214 ↗
3. 10.1172/JCI20031721510.1172/JCI200317215 ↗
4. 10.1002/jbmr.473910.1002/jbmr.4739 ↗
5. 10.1007/s11657-019-0674-210.1007/s11657-019-0674-2 ↗
6. 10.1016/j.jot.2022.06.00710.1016/j.jot.2022.06.007 ↗
7. 10.1002/jbmr.433510.1002/jbmr.4335 ↗
8. 10.1002/jbmr.333710.1002/jbmr.3337 ↗
9. 10.1016/j.bone.2017.08.00310.1016/j.bone.2017.08.003 ↗
10. 10.1016/j.jbo.2023.10047810.1016/j.jbo.2023.100478 ↗
11. 10.7150/thno.1713310.7150/thno.17133 ↗
12. 10.5966/sctm.2015-038610.5966/sctm.2015-0386 ↗
13. 10.1038/s41419-020-2530-010.1038/s41419-020-2530-0 ↗
14. 10.1161/STROKEAHA.121.03654510.1161/STROKEAHA.121.036545 ↗
15. 10.1038/s41467-022-29191-x10.1038/s41467-022-29191-x ↗
16. 10.1126/sciadv.abl643210.1126/sciadv.abl6432 ↗
17. 10.1038/s41467-022-33006-410.1038/s41467-022-33006-4 ↗
18. 10.1007/s11914-022-00756-510.1007/s11914-022-00756-5 ↗
19. 10.1016/j.jbspin.2019.07.01010.1016/j.jbspin.2019.07.010 ↗
20. 10.1016/j.bone.2023.11674910.1016/j.bone.2023.116749 ↗
21. 10.1002/adma.20210626510.1002/adma.202106265 ↗
22. 10.15252/embr.20215248110.15252/embr.202152481 ↗
23. 10.1002/hep.3183110.1002/hep.31831 ↗
24. 10.1038/s43018-022-00456-010.1038/s43018-022-00456-0 ↗
25. 10.1021/acsami.2c1918610.1021/acsami.2c19186 ↗
26. 10.1002/adhm.20230330010.1002/adhm.202303300 ↗
27. 10.3390/medicina5910175210.3390/medicina59101752 ↗
28. 10.1016/j.cell.2021.02.00210.1016/j.cell.2021.02.002 ↗
29. 10.1002/jcb.2894410.1002/jcb.28944 ↗
30. 10.1038/s12276-023-00956-810.1038/s12276-023-00956-8 ↗
31. 10.1080/21655979.2022.206728610.1080/21655979.2022.2067286 ↗
32. 10.1016/j.tox.2021.15307910.1016/j.tox.2021.153079 ↗
33. 10.7326/M20-088210.7326/M20-0882 ↗
34. 10.1002/jbmr.450310.1002/jbmr.4503 ↗
35. 10.1002/jbmr.333210.1002/jbmr.3332 ↗
36. 10.1016/j.biomaterials.2019.01.04910.1016/j.biomaterials.2019.01.049 ↗
37. 10.1093/abbs/gmab10210.1093/abbs/gmab102 ↗
38. 10.1172/JCI12313510.1172/JCI123135 ↗
39. 10.1002/adma.20220710710.1002/adma.202207107 ↗
40. 10.14336/ad.2023.0020510.14336/ad.2023.00205 ↗
41. 10.1126/sciadv.abn333310.1126/sciadv.abn3333 ↗
42. 10.1016/j.biomaterials.2022.12148210.1016/j.biomaterials.2022.121482 ↗
43. 10.1002/advs.20220145110.1002/advs.202201451 ↗
44. 10.1021/acs.nanolett.1c0215010.1021/acs.nanolett.1c02150 ↗
45. 10.1016/j.bioactmat.2021.02.01410.1016/j.bioactmat.2021.02.014 ↗
46. 10.1126/scitranslmed.aaz869710.1126/scitranslmed.aaz8697 ↗
47. 10.15252/embr.20215350910.15252/embr.202153509 ↗
48. 10.1038/s41467-021-26302-y10.1038/s41467-021-26302-y ↗