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CD142-positive synovial fibroblasts drive meniscus destruction in rheumatoid arthritis

Author

Listed:
  • Hao Sun

    (Sun Yat-sen University)

  • Xiaobin Lin

    (Sun Yat-sen University)

  • Fangzhou Liu

    (Sun Yat-sen University)

  • Yingbin Zhang

    (Sun Yat-sen University)

  • Jianda Ma

    (Sun Yat-sen University)

  • Zhencheng Huang

    (Sun Yat-sen University)

  • Junming Huang

    (Sun Yat-sen University)

  • Lutian Yao

    (China Medical University)

  • Mengyuan Zhang

    (Sun Yat-sen University)

  • Meiyi Chen

    (Sun Yat-sen University)

  • Jie Xu

    (Sun Yat-sen University)

  • Yulong Wei

    (Huazhong University of Science and Technology)

  • Lie Dai

    (Sun Yat-sen University)

  • Ruofan Ma

    (Sun Yat-sen University)

Abstract

Previous evidence suggest bone and cartilage damage is the main pathogenesis of rheumatoid arthritis joint destruction. However, the role of meniscus usually has not been thoroughly explored. Here, we identify CD142+ synovial fibroblasts as a subset located at sublining layer in normal and osteoarthritis synovium, which is increased and distributed at lining layer in rheumatoid arthritis synovium. Injection of CD142+ fibroblasts into DBA/1 male mice’s knee destructs meniscus but has slight effect on cartilage. ABCC4 is highly expressed in CD142+ fibroblasts, whose blockage by MK571 attenuates CD142+ fibroblasts-induced meniscus destruction through cAMP/PKA signaling. Long-term follow-up of rheumatoid arthritis cohort indicates that enriched CD142+ fibroblasts at lining layer are a risk factor for severe knee joint destruction and eventually undergo total knee arthroplasty. Our results demonstrate CD142+ fibroblasts as an indicator to assess prognosis and a therapeutic target to inhibit meniscal destruction, thereby alleviating rheumatoid arthritis knee joint damage.

Suggested Citation

  • Hao Sun & Xiaobin Lin & Fangzhou Liu & Yingbin Zhang & Jianda Ma & Zhencheng Huang & Junming Huang & Lutian Yao & Mengyuan Zhang & Meiyi Chen & Jie Xu & Yulong Wei & Lie Dai & Ruofan Ma, 2025. "CD142-positive synovial fibroblasts drive meniscus destruction in rheumatoid arthritis," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61842-7
    DOI: 10.1038/s41467-025-61842-7
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    References listed on IDEAS

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    1. Xunyao Wu & Yi Liu & Shanzhao Jin & Min Wang & Yuhao Jiao & Bo Yang & Xin Lu & Xin Ji & Yunyun Fei & Huaxia Yang & Lidan Zhao & Hua Chen & Yaran Zhang & Hao Li & Peter E. Lipsky & George C. Tsokos & F, 2021. "Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Kevin Wei & Ilya Korsunsky & Jennifer L. Marshall & Anqi Gao & Gerald F. M. Watts & Triin Major & Adam P. Croft & Jordan Watts & Philip E. Blazar & Jeffrey K. Lange & Thomas S. Thornhill & Andrew File, 2020. "Notch signalling drives synovial fibroblast identity and arthritis pathology," Nature, Nature, vol. 582(7811), pages 259-264, June.
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