Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats

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 microenvironm...

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Main Authors: Yang Feng, Rong Zhang, Yi-rong Wang, Fei Chen, Qiang Luo, Chuan Cai, Yang Jiao, Peng Xue
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/6618943
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author Yang Feng
Rong Zhang
Yi-rong Wang
Fei Chen
Qiang Luo
Chuan Cai
Yang Jiao
Peng Xue
author_facet Yang Feng
Rong Zhang
Yi-rong Wang
Fei Chen
Qiang Luo
Chuan Cai
Yang Jiao
Peng Xue
author_sort Yang Feng
collection DOAJ
description 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.
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institution Kabale University
issn 1687-966X
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language English
publishDate 2021-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-3f51d4061e1b42f184cada1b00283f032025-02-03T01:24:12ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/66189436618943Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in RatsYang Feng0Rong Zhang1Yi-rong Wang2Fei Chen3Qiang Luo4Chuan Cai5Yang Jiao6Peng Xue7Institute of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, ChinaState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi Province 710032, ChinaInstitute of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Stomatology, The 7th Medical Center, Chinese PLA General Hospital, Beijing 100700, ChinaInstitute of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, ChinaThis 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.http://dx.doi.org/10.1155/2021/6618943
spellingShingle Yang Feng
Rong Zhang
Yi-rong Wang
Fei Chen
Qiang Luo
Chuan Cai
Yang Jiao
Peng Xue
Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats
Stem Cells International
title Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats
title_full Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats
title_fullStr Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats
title_full_unstemmed Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats
title_short Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats
title_sort inhibition of endoplasmic reticulum stress by 4 phenyl butyric acid presents therapeutic effects on periodontitis experimental studies in vitro and in rats
url http://dx.doi.org/10.1155/2021/6618943
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