DataVXACS NanoPaper
journal article·2025-12-09

Interferon-γ-Induced Mesenchymal Stem Cell Exosomes Attenuate Chondrocyte Senescence and Osteoarthritis Progression by Hsp70

Senrui Liu, Junyu Mou, Zhu Xiong, Jiacheng Liu, Chengcheng Du, Zhenglin Zhu, Jianye Tan, Shengwen Cheng, Xianlin Qiu, Wei Huang, Yiting Lei, Junyi Liao

ACS Nano· Volume 19· Issue 48
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Source abstract

Abstract

With the accelerating pace of population aging, the incidence of osteoarthritis (OA), a degenerative disease strongly associated with age, is rapidly increasing. Chondrocyte senescence is a major contributor to cartilage degeneration; however, effective therapeutic strategies targeting chondrocyte aging remain lacking. Mesenchymal stem cell (MSC)-based approaches have emerged as a promising means of combating cellular senescence, among which exosomes (Exos) play a pivotal role in mediating therapeutic effects. Compared with direct MSC transplantation, Exos offer a safer and more ethically acceptable alternative. Moreover, the functional properties of Exos can be modulated by the microenvironmental stimuli applied to MSCs, although the underlying molecular mechanisms remain largely unclear. In this study, we employed interferon-γ (IFN-γ) to precondition MSCs and generate functionally enhanced Exos (iExos). Both in vitro and in vivo experiments demonstrated that iExos exhibit superior antisenescent activity in chondrocytes and more effectively attenuate OA progression. Sequencing analysis, together with mechanistic studies, revealed that iExos exert these effects by sustaining mitochondrial AMPK-SIRT3 homeostasis in chondrocytes through Hsp70. These findings partially elucidate a key pathway by which stem cell-derived iExos combat chondrocyte senescence and may inform the design of stable, efficient, and safe MSC-based antisenescence strategies.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · Osteoarthritis Treatment and Mechanisms · Mesenchymal stem cell research

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

Affiliations

Department of Orthopaedic Surgery, Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine/Orthopaedic Research Laboratory

The First Affiliated Hospital of Chongqing Medical University

Department of Pulmonary and Critical Care Medicine

Key Laboratory of Multi-Cell Systems, Center for Excellence in Molecular Cell Science

Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences

Department of Orthopaedic Surgery

The Second Affiliated Hospital of Chongqing Medical University

Department of Emergency Medicine of The First Affiliated Hospital of Chongqing Medical University

Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong SAR 999077, China

Funding

Natural Science Foundation of Chongqing Municipality · China Postdoctoral Science Foundation · National Natural Science Foundation of China · Chongqing Graduate Research and Innovation Project · Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) · Chongqing Medical Youth Top-notch Talent Program · ?Qiande? Talent Program?Outstanding Youth of The First Affiliated Hospital of Chongqing Medical University · Major Science and Technology Innovative Project of Chongqing Medical University · Hong Kong Scholars Program · "Dengfeng" Discipline Program-Clinical Major Project of The First Affiliated Hospital of Chongqing Medical University · Science and Technology Research Program of Chongqing Education Commission · Graduate Research Innovation Project of the First Affiliated Hospital of Chongqing Medical University · CQMU Program for Youth Innovation in Future Medicine

References (68)

Show source-provided references
1. 10.1093/rheumatology/keh10210.1093/rheumatology/keh102 ↗
2. 10.1186/s13075-025-03587-810.1186/s13075-025-03587-8 ↗
3. 10.1016/j.gendis.2023.02.00810.1016/j.gendis.2023.02.008 ↗
4. 10.1038/nrrheum.2016.6510.1038/nrrheum.2016.65 ↗
5. 10.1016/j.mcna.2019.10.00710.1016/j.mcna.2019.10.007 ↗
6. 10.1002/INMD.2024001510.1002/INMD.20240015 ↗
7. 10.1038/nm.400010.1038/nm.4000 ↗
8. 10.1152/physrev.00020.201810.1152/physrev.00020.2018 ↗
9. 10.59717/j.xinn-med.2025.10010910.59717/j.xinn-med.2025.100109 ↗
10. 10.1016/j.bmt.2025.10010210.1016/j.bmt.2025.100102 ↗
11. 10.1038/s41584-020-00533-710.1038/s41584-020-00533-7 ↗
12. 10.1016/j.biomaterials.2025.12319510.1016/j.biomaterials.2025.123195 ↗
13. 10.1186/s12951-023-02036-510.1186/s12951-023-02036-5 ↗
14. 10.1002/adhm.20240198510.1002/adhm.202401985 ↗
15. 10.59717/j.xinn-med.2025.10013210.59717/j.xinn-med.2025.100132 ↗
16. 10.1038/nrrheum.2010.19610.1038/nrrheum.2010.196 ↗
17. 10.1016/j.gendis.2022.12.01610.1016/j.gendis.2022.12.016 ↗
18. 10.1016/j.bmt.2025.10011510.1016/j.bmt.2025.100115 ↗
19. 10.1021/acsmaterialslett.4c0210810.1021/acsmaterialslett.4c02108 ↗
20. 10.1177/002203451770877010.1177/0022034517708770 ↗
21. 10.1016/j.gendis.2023.10115910.1016/j.gendis.2023.101159 ↗
22. 10.1016/j.redox.2021.10193210.1016/j.redox.2021.101932 ↗
23. 10.1186/s12951-025-03216-110.1186/s12951-025-03216-1 ↗
24. 10.1186/s12967-020-02622-310.1186/s12967-020-02622-3 ↗
25. 10.1002/VIW.2023011010.1002/VIW.20230110 ↗
26. 10.1002/VIW.2024002910.1002/VIW.20240029 ↗
27. 10.1002/INMD.2024001110.1002/INMD.20240011 ↗
28. 10.1126/science.aau697710.1126/science.aau6977 ↗
29. 10.1002/brx2.6610.1002/brx2.66 ↗
30. 10.1016/j.pharmthera.2019.04.00510.1016/j.pharmthera.2019.04.005 ↗
31. 10.1002/advs.20210322210.1002/advs.202103222 ↗
32. 10.1002/INMD.2023005510.1002/INMD.20230055 ↗
33. 10.1186/s12951-023-02211-810.1186/s12951-023-02211-8 ↗
34. 10.1002/smll.20200723510.1002/smll.202007235 ↗
35. 10.1186/s13287-015-0178-y10.1186/s13287-015-0178-y ↗
36. 10.1021/acsnano.2c0289810.1021/acsnano.2c02898 ↗
37. 10.1038/s41598-022-17692-010.1038/s41598-022-17692-0 ↗
38. 10.1186/s12967-015-0642-610.1186/s12967-015-0642-6 ↗
39. 10.1002/VIW.2023000410.1002/VIW.20230004 ↗
40. 10.17219/acem/6143110.17219/acem/61431 ↗
41. 10.1016/j.ebiom.2017.03.02010.1016/j.ebiom.2017.03.020 ↗
42. 10.1038/s41580-019-0133-310.1038/s41580-019-0133-3 ↗
43. 10.1098/rsob.20008910.1098/rsob.200089 ↗
44. 10.1038/s12276-022-00745-910.1038/s12276-022-00745-9 ↗
45. 10.1016/j.intimp.2022.10860010.1016/j.intimp.2022.108600 ↗
46. 10.34133/research.028110.34133/research.0281 ↗
47. 10.34133/research.019210.34133/research.0192 ↗
48. 10.34133/research.043310.34133/research.0433 ↗
49. 10.1146/annurev-physiol-021115-10501110.1146/annurev-physiol-021115-105011 ↗
50. 10.1038/s43587-022-00340-710.1038/s43587-022-00340-7 ↗
51. 10.1002/EXP.2023007810.1002/EXP.20230078 ↗
52. 10.26599/NBE.2023.929003510.26599/NBE.2023.9290035 ↗
53. 10.1038/nrm.2017.11010.1038/nrm.2017.110 ↗
54. 10.26599/NBE.2024.929005510.26599/NBE.2024.9290055 ↗
55. 10.1038/cr.2018.1610.1038/cr.2018.16 ↗
56. 10.1002/mba2.7001710.1002/mba2.70017 ↗
57. 10.1016/j.arr.2023.10195510.1016/j.arr.2023.101955 ↗
58. 10.3390/ijms2215807710.3390/ijms22158077 ↗
59. 10.1073/pnas.151613111210.1073/pnas.1516131112 ↗
60. 10.1002/EXP.2022013210.1002/EXP.20220132 ↗
61. 10.1038/nrm.2017.9510.1038/nrm.2017.95 ↗
62. 10.7150/thno.3039810.7150/thno.30398 ↗
63. 10.1002/adma.20230329910.1002/adma.202303299 ↗
64. 10.1007/s40820-024-01464-810.1007/s40820-024-01464-8 ↗
65. 10.1007/s40820-024-01353-010.1007/s40820-024-01353-0 ↗
66. 10.1007/s40820-025-01662-y10.1007/s40820-025-01662-y ↗
67. 10.1002/EXP.2023014910.1002/EXP.20230149 ↗
68. 10.1002/marc.20230067010.1002/marc.202300670 ↗