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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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8682 |
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| author | Zijiao Zhang Juhan Song Seung-Hee Kwon Zhao Wang Suk-Gyun Park Xianyu Piao Je-Hwang Ryu Nacksung Kim Ok-Su Kim Sun-Hun Kim Jeong-Tae Koh |
| author_facet | Zijiao Zhang Juhan Song Seung-Hee Kwon Zhao Wang Suk-Gyun Park Xianyu Piao Je-Hwang Ryu Nacksung Kim Ok-Su Kim Sun-Hun Kim Jeong-Tae Koh |
| author_sort | Zijiao Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T03:40:11Z |
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| id | doaj.art-08f71deed57c4d13bf7b28db0b29c18a |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:11Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-08f71deed57c4d13bf7b28db0b29c18a2023-11-18T01:39:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410868210.3390/ijms24108682Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in MiceZijiao Zhang0Juhan Song1Seung-Hee Kwon2Zhao Wang3Suk-Gyun Park4Xianyu Piao5Je-Hwang Ryu6Nacksung Kim7Ok-Su Kim8Sun-Hun Kim9Jeong-Tae Koh10Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaHard-Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaHard-Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaHard-Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of KoreaThere 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.https://www.mdpi.com/1422-0067/24/10/8682pirfenidoneperiodontitisosteoclast differentiationalveolar bone lossinflammationNF-κB pathway |
| spellingShingle | Zijiao Zhang Juhan Song Seung-Hee Kwon Zhao Wang Suk-Gyun Park Xianyu Piao Je-Hwang Ryu Nacksung Kim Ok-Su Kim Sun-Hun Kim Jeong-Tae Koh Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice International Journal of Molecular Sciences pirfenidone periodontitis osteoclast differentiation alveolar bone loss inflammation NF-κB pathway |
| 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 | pirfenidone periodontitis osteoclast differentiation alveolar bone loss inflammation NF-κB pathway |
| url | https://www.mdpi.com/1422-0067/24/10/8682 |
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