Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression
Abstract 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 osteoar...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59861-5 |
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| author | Na Liu Yuze Ma Wang Gong Xiaoyan Shao Tianshu Shi Lan Li Wenshu Wu Xiang Chen Yong Shi Pan Zhang Jiaquan Lin Chengzhi Wang Depeng Fang Lin Yang Pu Wang Wentian Gao Yi He Xueying An Rui Du Ying Chen Bin Liu Jianghui Qin Dongyang Chen Pingqiang Cai Qing Jiang Baosheng Guo |
| author_facet | Na Liu Yuze Ma Wang Gong Xiaoyan Shao Tianshu Shi Lan Li Wenshu Wu Xiang Chen Yong Shi Pan Zhang Jiaquan Lin Chengzhi Wang Depeng Fang Lin Yang Pu Wang Wentian Gao Yi He Xueying An Rui Du Ying Chen Bin Liu Jianghui Qin Dongyang Chen Pingqiang Cai Qing Jiang Baosheng Guo |
| author_sort | Na Liu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-33d25d16d3eb4203bb3a842abdec3502 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-33d25d16d3eb4203bb3a842abdec35022025-08-20T03:08:43ZengNature PortfolioNature Communications2041-17232025-05-0116112210.1038/s41467-025-59861-5Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progressionNa Liu0Yuze Ma1Wang Gong2Xiaoyan Shao3Tianshu Shi4Lan Li5Wenshu Wu6Xiang Chen7Yong Shi8Pan Zhang9Jiaquan Lin10Chengzhi Wang11Depeng Fang12Lin Yang13Pu Wang14Wentian Gao15Yi He16Xueying An17Rui Du18Ying Chen19Bin Liu20Jianghui Qin21Dongyang Chen22Pingqiang Cai23Qing Jiang24Baosheng Guo25State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityBranch of National Clinical Research Center for Orthopedics, Sports Medicine and RehabilitationState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityAbstract 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.https://doi.org/10.1038/s41467-025-59861-5 |
| spellingShingle | Na Liu Yuze Ma Wang Gong Xiaoyan Shao Tianshu Shi Lan Li Wenshu Wu Xiang Chen Yong Shi Pan Zhang Jiaquan Lin Chengzhi Wang Depeng Fang Lin Yang Pu Wang Wentian Gao Yi He Xueying An Rui Du Ying Chen Bin Liu Jianghui Qin Dongyang Chen Pingqiang Cai Qing Jiang Baosheng Guo Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression Nature Communications |
| title | Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression |
| title_full | Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression |
| title_fullStr | Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression |
| title_full_unstemmed | Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression |
| title_short | Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression |
| title_sort | osteocyte derived extracellular vesicles mediate the bone to cartilage crosstalk and promote osteoarthritis progression |
| url | https://doi.org/10.1038/s41467-025-59861-5 |
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