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Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice

There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodonti...

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Autores principales: Zhang, Zijiao, Song, Juhan, Kwon, Seung-Hee, Wang, Zhao, Park, Suk-Gyun, Piao, Xianyu, Ryu, Je-Hwang, Kim, Nacksung, Kim, Ok-Su, Kim, Sun-Hun, Koh, Jeong-Tae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218211/
https://www.ncbi.nlm.nih.gov/pubmed/37240020
http://dx.doi.org/10.3390/ijms24108682
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author Zhang, Zijiao
Song, Juhan
Kwon, Seung-Hee
Wang, Zhao
Park, Suk-Gyun
Piao, Xianyu
Ryu, Je-Hwang
Kim, Nacksung
Kim, Ok-Su
Kim, Sun-Hun
Koh, Jeong-Tae
author_facet Zhang, Zijiao
Song, Juhan
Kwon, Seung-Hee
Wang, Zhao
Park, Suk-Gyun
Piao, Xianyu
Ryu, Je-Hwang
Kim, Nacksung
Kim, Ok-Su
Kim, Sun-Hun
Koh, Jeong-Tae
author_sort Zhang, Zijiao
collection PubMed
description There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodontitis was established by ligating the unilateral maxillary second molar for 7 days in mice (n = 8 per group), and PFD was administered daily via intraperitoneal injection. The micro-computed tomography and histology analyses were performed to determine changes in the alveolar bone following the PFD administration. For in vitro analysis, bone marrow macrophages (BMMs) were isolated from mice and cultured with PFD in the presence of RANKL or LPS. The effectiveness of PFD on osteoclastogenesis, inflammatory cytokine expression, and NF-κB activation was determined with RT-PCR, Western blot, and immunofluorescence analyses. PFD treatment significantly inhibited the ligature-induced alveolar bone loss, with decreases in TRAP-positive osteoclasts and expression of inflammatory cytokines in mice. In cultured BMM cells, PFD also inhibited RANKL-induced osteoclast differentiation and LPS-induced proinflammatory cytokine (IL-1β, IL-6, TNF-a) expression via suppressing the NF-κB signal pathway. These results suggest that PFD can suppress periodontitis progression by inhibiting osteoclastogenesis and inflammatory cytokine production via inhibiting the NF-κB signal pathway, and it may be a promising candidate for controlling periodontitis.
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spelling pubmed-102182112023-05-27 Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice Zhang, Zijiao Song, Juhan Kwon, Seung-Hee Wang, Zhao Park, Suk-Gyun Piao, Xianyu Ryu, Je-Hwang Kim, Nacksung Kim, Ok-Su Kim, Sun-Hun Koh, Jeong-Tae Int J Mol Sci Article There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodontitis was established by ligating the unilateral maxillary second molar for 7 days in mice (n = 8 per group), and PFD was administered daily via intraperitoneal injection. The micro-computed tomography and histology analyses were performed to determine changes in the alveolar bone following the PFD administration. For in vitro analysis, bone marrow macrophages (BMMs) were isolated from mice and cultured with PFD in the presence of RANKL or LPS. The effectiveness of PFD on osteoclastogenesis, inflammatory cytokine expression, and NF-κB activation was determined with RT-PCR, Western blot, and immunofluorescence analyses. PFD treatment significantly inhibited the ligature-induced alveolar bone loss, with decreases in TRAP-positive osteoclasts and expression of inflammatory cytokines in mice. In cultured BMM cells, PFD also inhibited RANKL-induced osteoclast differentiation and LPS-induced proinflammatory cytokine (IL-1β, IL-6, TNF-a) expression via suppressing the NF-κB signal pathway. These results suggest that PFD can suppress periodontitis progression by inhibiting osteoclastogenesis and inflammatory cytokine production via inhibiting the NF-κB signal pathway, and it may be a promising candidate for controlling periodontitis. MDPI 2023-05-12 /pmc/articles/PMC10218211/ /pubmed/37240020 http://dx.doi.org/10.3390/ijms24108682 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Zijiao
Song, Juhan
Kwon, Seung-Hee
Wang, Zhao
Park, Suk-Gyun
Piao, Xianyu
Ryu, Je-Hwang
Kim, Nacksung
Kim, Ok-Su
Kim, Sun-Hun
Koh, Jeong-Tae
Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice
title Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice
title_full Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice
title_fullStr Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice
title_full_unstemmed Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice
title_short Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice
title_sort pirfenidone inhibits alveolar bone loss in ligature-induced periodontitis by suppressing the nf-κb signaling pathway in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218211/
https://www.ncbi.nlm.nih.gov/pubmed/37240020
http://dx.doi.org/10.3390/ijms24108682
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