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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
KimJiheeRyuGinaSeoJeongminGoMiyeonGyungminYiSolSuwonLeeHanaJune-YongHan SungParkMin-ChanShinDong HaeShimHyunboWankyuSoo Young
Ewha Authors
이수영신동해심현보김완규김수원김지희
SCOPUS Author ID
이수영scopusscopus; 신동해scopus; 심현보scopus; 김완규scopus; 김수원scopus; 김지희scopus
Issue Date
2024
Journal Title
Nature Communications
ISSN
2041-1723JCR Link
Citation
Nature Communications vol. 15, no. 1
Publisher
Nature Research
Indexed
SCIE; SCOPUS WOS 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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