2. Academic Validation
  3. Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression

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

  • Nat Commun. 2025 May 22;16(1):4746. doi: 10.1038/s41467-025-59861-5.
Na Liu 1 2,  Yuze Ma 1 2,  Wang Gong 1 2,  Xiaoyan Shao 1 2,  Tianshu Shi 1 2,  Lan Li 1 2,  Wenshu Wu 1 2,  Xiang Chen 1 2,  Yong Shi 1 2,  Pan Zhang 1 2,  Jiaquan Lin 1 2,  Chengzhi Wang 1 2,  Depeng Fang 1 2,  Lin Yang 1 2,  Pu Wang 1 2,  Wentian Gao 1 2,  Yi He 1 2,  Xueying An 1 2,  Rui Du 2 3,  Ying Chen 1 2,  Bin Liu 1 2,  Jianghui Qin 1 2,  Dongyang Chen 1 2,  Pingqiang Cai 4 5,  Qing Jiang 6 7,  Baosheng Guo 8 9
Affiliations

Affiliations

  • 1 State 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 University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China.
  • 2 Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing, PR China.
  • 3 Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Xuzhou Medical University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China.
  • 4 State 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 University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China. pqcai@nju.edu.cn.
  • 5 Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing, PR China. pqcai@nju.edu.cn.
  • 6 State 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 University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China. qingj@nju.edu.cn.
  • 7 Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing, PR China. qingj@nju.edu.cn.
  • 8 State 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 University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China. borisguo@nju.edu.cn.
  • 9 Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing, PR China. borisguo@nju.edu.cn.
PMID: 40399261 DOI: 10.1038/s41467-025-59861-5
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.

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