Semi-synthetic chondroitin sulfate CS-semi5 upregulates miR-122-5p, conferring a therapeutic effect on osteoarthritis via the p38/MMP13 pathway

Autor: Xiang Li, Ya Zhou, Xuefeng Chen, Hongjun Wang, Shuang Yang, Jun Yang, Yunfeng Song, Zhehui Zhao, Haijing Zhang, Lianqiu Wu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Acta Pharmaceutica Sinica B, Vol 14, Iss 8, Pp 3528-3542 (2024)
Druh dokumentu: article
ISSN: 2211-3835
89068998
DOI: 10.1016/j.apsb.2024.05.016
Popis: Osteoarthritis (OA) is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage. Traditional treatments for OA are limited to alleviating various OA symptoms. There is a lack of drugs available in clinical practice that can truly repair cartilage damage. Here, we developed the chondroitin sulfate analog CS-semi5, semi-synthesized from chondroitin sulfate A. In vivo, CS-semi5 alleviated inflammation, provided analgesic effects, and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model. A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats, revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment. Binding prediction revealed that miR-122-5p acted on the 3′-untranslated region of p38 mitogen-activated protein kinase, which was related to MMP13 regulation. Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis, which was further validated in the articular cartilage of OA rats. This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5, revealing its cartilage-protecting, anti-inflammatory, and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.
Databáze: Directory of Open Access Journals
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