Cholic acid mitigates osteoarthritis by inhibiting the NF-κB/PERK/ SIRT1 signaling pathway

作     者：JIAOE SHENG ZUMIN YI SANSHAN HE QINGCHAO WU XIA HUANG GUOQING YAN YUFANG DAI LINCHONG SU 

作者机构：The Minda Hospital of Hubei Minzu UniversityHubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic DiseaseEnshi445000China The Obstetrics and Gynecology of Jianshi County Hospital of Traditional Chinese MedicineEnshi445300China 

出 版 物：《BIOCELL》 (生物细胞（英文）)

年 卷 期：2024年第48卷第7期

页      面：1095-1104页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：This work was financially supported by the Open Fund for Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases(PT022311) 

主　　题：Cholic acid Cartilage Inflammation RNA sequencing Differentially expressed genes 

摘      要：Introduction:Cholic acid(CA)is a natural steroid useful in treating chronic bronchitis and *** the other hand,its potential impact on osteoarthritis(OA)is ***:Using an in vitro and in vivo osteoarthritis model,we sought to assess the chondroprotective properties of ***:We employed the Cell Counting Kit-8 to measure the impact of CA on chondrocyte activity to assess the toxicity of the *** molecular biology experimental techniques were used to investigate potential signaling pathways that CA may use to prevent inflammation and give chondrocytes ***,how CA affects the OA model in Sprague-Dawley(SD)rats was ***:CA significantly suppressed the up-regulation of the interleukin-1β(IL-1β),cyclooxygenase-2(COX-2),and matrix metalloproteinase 13(MMP-13)and the downregulation of aggrecan and type II collagen A1(COL2A)in chondrocytes treated tumor necrosis factor-alpha(TNF-α).Differentially expressed genes(DEG)enrichment revealed IL-17,TNF,chemokine,cytokine-cytokine receptor,toll-like receptor,and nucleotide oligomerization domain-like receptor were the primary signaling *** enriched DEGs included CXCL6,CCL20,MMP3,CXCL3,CXCL11,CCL5,CXCL10,MMP9,MMP13,and CXCL2;these DEGs are involved in inflammatory responses and their expression induced by TNF-αwas reversed by CA *** inhibits p65 nuclear translocation and inhibitory subunit kappa B alpha(IκBα)phosphorylation induced by TNF-α.Furthermore,CA attenuated protein expression of protein kinase RNA-like endoplasmic reticulum kinase(PERK),inositol-requiring transmembrane kinase/endoribonuclease 1α(IRE1α),glucose regulatory protein 78(GRP78),and sirtuin 1(SIRT1),and down-regulation of phosphorylation of AMP-activated protein kinase-α(p-AMPKα)in TNF-α-treated ***:CA significantly ameliorated cartilage degradation in the OA rat *** alleviated the inflammatory response through the nuclear factor kappa B/PERK/SIRT1 axis and