摘要
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 30-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 cartilageprotecting,anti-inflammatory,and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.
基金
supported by CAMS Innovation Fund for Medical Sciences(2022-I2M-2-002 and 2022-I2M-1e014,China)
the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-JKCS-019,China).
