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

作　　者：Xiang Li Ya Zhou Xuefeng Chen Hongjun Wang Shuang Yang Jun Yang Yunfeng Song Zhehui Zhao Haijing Zhang Lianqiu Wu 

机构地区：[1]State Key Laboratory of Digestive Health,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China [2]Tide Pharmaceutical Co.,Ltd.,Beijing 100176,China [3]Camford Royal School,Beijing 100093,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第8期3528-3542,共15页药学学报（英文版）

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).

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.

关 键 词：Chondroitin sulfate Cartilage OSTEOARTHRITIS Extracellular matrix Inflammation miRNA P38 MMP13 

分 类 号：R730.51[医药卫生—肿瘤]