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Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies

Authors :
Yang, Feng
Rong, Zhang
Yi-Rong, Wang
Fei, Chen
Qiang, Luo
Chuan, Cai
Yang, Jiao
Peng, Xue
Source :
Stem Cells International
Publication Year :
2020

Abstract

This study investigated the probable mechanisms of endoplasmic reticulum (ER) stress involved in periodontitis in vitro and in vivo. We isolated periodontal ligament stem cells from periodontitis patients and healthy controls (P-PDLSCs and H-PDLSCs). To further simulate the periodontal microenvironment in patients, lipopolysaccharide (LPS) was used to treat H-PDLSCs. The results showed that periodontitis-related inflammation gave rise to the upregulated expression levels of ER stress representative genes including GRP78, PERK, ATF4, and CHOP. In contrast, the treatment of 4-phenyl butyric acid (4-PBA) remarkably suppressed ER stress and supported cell viability. The increased secretion of proinflammatory factors like TNF-α, IL-1β, and IL-6 and the activation of NF-κB pathway were also attenuated by 4-PBA treatment. Moreover, 4-PBA treatment restored the impaired osteogenic differentiation ability of PDLSCs, as demonstrated by the upregulated expression levels of Runx2 and OCN as well as the enhanced Alizarin red staining. Local administration of 4-PBA could rescue alveolar bone resorption of LPS-induced periodontitis rats. Thus, our findings suggested ER stress might act as a promising therapeutic target against periodontitis.

Subjects

Subjects :
Research Article

Details

ISSN :
1687966X
Volume :
2021
Database :
OpenAIRE
Journal :
Stem cells international
Accession number :
edsair.pmid..........05c261814050345f3e2819c679e6fa5b