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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Wiley
2021-01-01
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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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id | doaj-art-3f51d4061e1b42f184cada1b00283f03 |
institution | Kabale University |
issn | 1687-966X 1687-9678 |
language | English |
publishDate | 2021-01-01 |
publisher | Wiley |
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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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