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CD142-positive synovial fibroblasts drive meniscus destruction in rheumatoid arthritis

Hao Sun1, Xiaobin Lin1, Fangzhou Liu1

  • 1Department of Joint Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Nature Communications
|July 28, 2025
PubMed

Insights

CD142+ fibroblasts in rheumatoid arthritis synovium drive meniscus destruction. Blocking ABCC4 with MK571 inhibits this damage, offering a new therapeutic target for knee joint preservation.

Area of Science:

  • Rheumatology
  • Cell Biology
  • Immunology

Background:

  • Rheumatoid arthritis (RA) primarily affects joints, with bone and cartilage damage being key features.
  • The role of the meniscus in RA pathogenesis has been under-explored.
  • Synovial fibroblasts are implicated in joint inflammation and destruction.

Purpose of the Study:

  • To investigate the role of CD142+ synovial fibroblasts in rheumatoid arthritis (RA) joint destruction.
  • To identify the mechanisms underlying CD142+ fibroblast-mediated meniscus damage.
  • To evaluate CD142+ fibroblasts as a prognostic indicator and therapeutic target in RA.

Main Methods:

  • Identification and characterization of CD142+ fibroblasts in normal, osteoarthritis, and rheumatoid arthritis synovium.
  • In vivo experiments injecting CD142+ fibroblasts into mouse knees.
  • Pharmacological inhibition of ABCC4 using MK571.
  • Analysis of cAMP/PKA signaling pathways.
  • Long-term follow-up of an RA patient cohort.

Main Results:

  • CD142+ fibroblasts are increased and located at the lining layer in RA synovium.
  • Injection of CD142+ fibroblasts into mouse knees caused significant meniscus destruction.
  • ABCC4 is highly expressed in CD142+ fibroblasts; its blockage attenuated meniscus destruction via cAMP/PKA signaling.
  • Enriched CD142+ fibroblasts in RA patients correlated with severe knee destruction and need for total knee arthroplasty.

Conclusions:

  • CD142+ synovial fibroblasts are a key driver of meniscus destruction in rheumatoid arthritis.
  • Targeting ABCC4 in CD142+ fibroblasts presents a potential therapeutic strategy to prevent RA-induced knee damage.
  • CD142+ fibroblasts serve as a valuable prognostic biomarker for severe joint destruction in RA.

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