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5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis
- Title
- 5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis
- Authors
- Kim; Jihee; Ryu; Gina; Seo; Jeongmin; Go; Miyeon; Gyungmin; Yi; Sol; Suwon; Lee; Hana; June-Yong; Han Sung; Park; Min-Chan; Shin; Dong Hae; Shim; Hyunbo; Wankyu; Soo Young
- Ewha Authors
- 이수영; 신동해; 심현보; 김완규; 김수원; 김지희
- SCOPUS Author ID
- 이수영; 신동해; 심현보; 김완규; 김수원; 김지희
- Issue Date
- 2024
- Journal Title
- Nature Communications
- ISSN
- 2041-1723
- Citation
- Nature Communications vol. 15, no. 1
- Publisher
- Nature Research
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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. © The Author(s) 2024.
- DOI
- 10.1038/s41467-024-45174-6
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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