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5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis

Author

Listed:
  • Jihee Kim

    (Ewha Womans University
    Ewha Womans University)

  • Gina Ryu

    (Ewha Womans University)

  • Jeongmin Seo

    (Ewha Womans University)

  • Miyeon Go

    (Ewha Womans University)

  • Gyungmin Kim

    (Ewha Womans University)

  • Sol Yi

    (Ewha Womans University)

  • Suwon Kim

    (Ewha Womans University)

  • Hana Lee

    (Yonsei University)

  • June-Yong Lee

    (Yonsei University College of Medicine)

  • Han Sung Kim

    (Yonsei University)

  • Min-Chan Park

    (Yonsei University College of Medicine)

  • Dong Hae Shin

    (Ewha Womans University)

  • Hyunbo Shim

    (Ewha Womans University)

  • Wankyu Kim

    (Ewha Womans University)

  • Soo Young Lee

    (Ewha Womans University
    Ewha Womans University
    Ewha Womans University)

Abstract

Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8–11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.

Suggested Citation

  • Jihee Kim & Gina Ryu & Jeongmin Seo & Miyeon Go & Gyungmin Kim & Sol Yi & Suwon Kim & Hana Lee & June-Yong Lee & Han Sung Kim & Min-Chan Park & Dong Hae Shin & Hyunbo Shim & Wankyu Kim & Soo Young Lee, 2024. "5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45174-6
    DOI: 10.1038/s41467-024-45174-6
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    References listed on IDEAS

    as
    1. Doo Ri Park & Jihee Kim & Gyeong Min Kim & Haeseung Lee & Minhee Kim & Donghyun Hwang & Hana Lee & Han-Sung Kim & Wankyu Kim & Min Chan Park & Hyunbo Shim & Soo Young Lee, 2020. "Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    2. Ferreira José A., 2007. "The Benjamini-Hochberg Method in the Case of Discrete Test Statistics," The International Journal of Biostatistics, De Gruyter, vol. 3(1), pages 1-18, July.
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