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조회353

류지나Gina Ryu

이화여자대학교

Nat. Commun., Feb 03 2024, 15 (1) | https://doi.org/10.1038/s41467-024-45174-6 5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis

Jihee Kim^1,2,8, Gina Ryu^1,8, Jeongmin Seo¹, Miyeon Go¹, Gyungmin Kim¹, Sol Yi¹, Suwon Kim³, Hana Lee⁴, June-Yong Lee⁵, Han Sung Kim⁴, Min-Chan Park⁶, Dong Hae Shin³, Hyunbo Shim¹, Wankyu Kim¹ & Soo Young Lee^1,2,7

¹Department of Life Science, Ewha Womans University, Seoul, Republic of Korea.

²The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Republic of Korea.

³Department of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.

⁴Department of Biomedical Engineering, Yonsei University, Wonju, Republic of Korea.

⁵Department 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.

⁶Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

⁷Multitasking Macrophage Research Center, Ewha Womans University, Seoul, Republic of Korea.

⁸These authors contributed equally: Jihee Kim, Gina Ryu.

Corresponding author : Correspondence to Soo Young Lee.

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.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-05)
연구진국내 연구진
분야 생명과학 > 면역학

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