2. Academic Validation
  3. 5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis

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

  • Nat Commun. 2024 Feb 3;15(1):1024. doi: 10.1038/s41467-024-45174-6.
Jihee Kim # 1 2,  Gina Ryu # 1,  Jeongmin Seo 1,  Miyeon Go 1,  Gyungmin Kim 1,  Sol Yi 1,  Suwon Kim 3,  Hana Lee 4,  June-Yong Lee 5,  Han Sung Kim 4,  Min-Chan Park 6,  Dong Hae Shin 3,  Hyunbo Shim 1,  Wankyu Kim 1,  Soo Young Lee 7 8 9
Affiliations

Affiliations

  • 1 Department of Life Science, Ewha Womans University, Seoul, Republic of Korea.
  • 2 The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Republic of Korea.
  • 3 Department of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
  • 4 Department of Biomedical Engineering, Yonsei University, Wonju, Republic of Korea.
  • 5 Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • 6 Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • 7 Department of Life Science, Ewha Womans University, Seoul, Republic of Korea. leesy@ewha.ac.kr.
  • 8 The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Republic of Korea. leesy@ewha.ac.kr.
  • 9 Multitasking Macrophage Research Center, Ewha Womans University, Seoul, Republic of Korea. leesy@ewha.ac.kr.
  • # Contributed equally.
PMID: 38310093 DOI: 10.1038/s41467-024-45174-6
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.

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