Open Access

ARTICLE

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

JIAOE SHENG¹, ZUMIN YI², SANSHAN HE¹, QINGCHAO WU¹, XIA HUANG¹, GUOQING YAN¹, YUFANG DAI^1,*, LINCHONG SU^1,*

1 The Minda Hospital of Hubei Minzu University, Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Disease, Enshi, 445000, China
2 The Obstetrics and Gynecology of Jianshi County Hospital of Traditional Chinese Medicine, Enshi, 445300, China

* Corresponding Authors: YUFANG DAI. Email: ; LINCHONG SU. Email:

(This article belongs to the Special Issue: Bioinformatics Study of Diseases)

BIOCELL 2024, 48(7), 1095-1104. https://doi.org/10.32604/biocell.2024.028421

Received 16 December 2022; Accepted 06 July 2023; Issue published 03 July 2024

Abstract

Introduction: Cholic acid (CA) is a natural steroid useful in treating chronic bronchitis and cholecystitis. On the other hand, its potential impact on osteoarthritis (OA) is unknown. Objective: Using an in vitro and in vivo osteoarthritis model, we sought to assess the chondroprotective properties of CA. Methods: We employed the Cell Counting Kit-8 to measure the impact of CA on chondrocyte activity to assess the toxicity of the cells. Multiple molecular biology experimental techniques were used to investigate potential signaling pathways that CA may use to prevent inflammation and give chondrocytes protection. Furthermore, how CA affects the OA model in Sprague-Dawley (SD) rats was evaluated. Results: CA significantly suppressed the up-regulation of the interleukin-1 β (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 pathways. The 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-α was reversed by CA treatment. 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 chondrocytes. Conclusions: CA significantly ameliorated cartilage degradation in the OA rat model. CA alleviated the inflammatory response through the nuclear factor kappa B/PERK/SIRT1 axis and ameliorated cartilage degradation.

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