Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression
Osteoarthritis is a common degenerative joint disease, in which mechanical overloading disrupts subchondral bone remodeling before cartilage degeneration and the osteocytes in the subchondral bone are mainly responsible for mechanosensing. However, their functional role in the early osteoarthritis is still unclear. Here we show that mechanical stress induces osteocytes in subchondral bone to secrete extracellular vesicles that accelerate cartilage metabolic dysregulation in patients with both sexes and male mice. The miR-23b-3p in extracellular vesicles promotes cartilage catabolism and inhibits anabolism by targeting OTUD4, disrupting mitophagy in chondrocytes. Inhibiting miR-23b-3p in osteocytes or chondrocytes reduces cartilage degeneration and osteoarthritis progression in male mice. Together, our findings highlight that osteocyte-derived extracellular vesicles mediate communication with chondrocytes and suggest miR-23b-3p as a potential therapeutic target for osteoarthritis.
Authors
- Pingqiang Cai (ORCID: https://orcid.org/0000-0002-2665-5932)
- Depeng Fang (ORCID: https://orcid.org/0000-0002-8346-9992)
- Jiaquan Lin
- Qing Jiang (ORCID: https://orcid.org/0000-0002-2552-9686)
- Yi He (ORCID: https://orcid.org/0000-0002-1752-8405)
- Wentian Gao
- Baosheng Guo (ORCID: https://orcid.org/0000-0002-4510-5418)
- Xiaoyan Shao (ORCID: https://orcid.org/0000-0003-3014-6820)
- Lan Li (ORCID: https://orcid.org/0000-0002-4635-6331)
- Ying Chen (ORCID: https://orcid.org/0000-0001-5148-6504)
- Na Liu (ORCID: https://orcid.org/0000-0003-3832-5591)
- Bin Liu (ORCID: https://orcid.org/0000-0001-9147-062X)
- Pan Zhang (ORCID: https://orcid.org/0000-0001-8279-4008)
- Xiang Chen (ORCID: https://orcid.org/0000-0002-2499-8261)
- Rui Du (ORCID: https://orcid.org/0000-0002-8183-6197)
- Dongyang Chen (ORCID: https://orcid.org/0000-0002-3746-8841)
- Chengzhi Wang (ORCID: https://orcid.org/0000-0003-4649-9567)
- Yong Shi
- Xueying An
- Wang Gong (ORCID: https://orcid.org/0000-0003-4920-5894)
- Lin Yang (ORCID: https://orcid.org/0000-0002-2240-3017)
- Jianghui Qin (ORCID: https://orcid.org/0000-0001-7294-7947)
- Yuze Ma (ORCID: https://orcid.org/0000-0003-0668-5752)
- Pu Wang (ORCID: https://orcid.org/0009-0006-1053-2352)
- Wenshu Wu
- T T Shi (ORCID: https://orcid.org/0000-0002-7147-4305)
Institutions
- Xuzhou Medical College (CN)
- National Clinical Research Center for Digestive Diseases (CN)
- Nanjing Drum Tower Hospital (CN)
- National Clinical Research (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1038/s41467-025-59861-5
- Citations
- 11
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 8.87