Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression

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 () and Baosheng Guo ()
Additional contact information
Na Liu: Nanjing University
Yuze Ma: Nanjing University
Wang Gong: Nanjing University
Xiaoyan Shao: Nanjing University
Tianshu Shi: Nanjing University
Lan Li: Nanjing University
Wenshu Wu: Nanjing University
Xiang Chen: Nanjing University
Yong Shi: Nanjing University
Pan Zhang: Nanjing University
Jiaquan Lin: Nanjing University
Chengzhi Wang: Nanjing University
Depeng Fang: Nanjing University
Lin Yang: Nanjing University
Pu Wang: Nanjing University
Wentian Gao: Nanjing University
Yi He: Nanjing University
Xueying An: Nanjing University
Rui Du: Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation
Ying Chen: Nanjing University
Bin Liu: Nanjing University
Jianghui Qin: Nanjing University
Dongyang Chen: Nanjing University
Pingqiang Cai: Nanjing University
Qing Jiang: Nanjing University
Baosheng Guo: Nanjing University

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59861-5

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