Deferoxamine Treatment Effectively Prevents Periodontitis Progression by Reducing Inflammation and Osteoclastogenesis in Experimental Periodontitis Rats

Yanlin Zhu,1,2 Shuwei Qiao,2,3 Yuxuan Pang,2,3 Huimin Wang,2,3 Yanmin Zhou1,2 1Department of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China; 2Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jili...

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Main Authors: Zhu Y, Qiao S, Pang Y, Wang H, Zhou Y
Format: Article
Language:English
Published: Dove Medical Press 2024-11-01
Series:Journal of Inflammation Research
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Online Access:https://www.dovepress.com/deferoxamine-treatment-effectively-prevents-periodontitis-progression--peer-reviewed-fulltext-article-JIR
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author Zhu Y
Qiao S
Pang Y
Wang H
Zhou Y
author_facet Zhu Y
Qiao S
Pang Y
Wang H
Zhou Y
author_sort Zhu Y
collection DOAJ
description Yanlin Zhu,1,2 Shuwei Qiao,2,3 Yuxuan Pang,2,3 Huimin Wang,2,3 Yanmin Zhou1,2 1Department of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China; 2Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China; 3Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yanmin Zhou, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 1500 Qinghua Road, Changchun, Jilin Province, 130021, People’s Republic of China, Tel +8618943971001, Email zhouym@jlu.edu.cnPurpose: Although the anti-inflammatory properties of the hypoxia-mimetic drug deferoxamine (DFO) have been reported, its potential as a treatment for periodontitis remains unknown. This study investigated the therapeutic benefits of DFO on osteoclastogenesis and inflammation in periodontitis progression.Methods: RAW264.7 cells were pretreated with DFO before stimulation with lipopolysaccharides from Porphyromonas gingivalis (P.g-LPS). Hypoxia-inducible factor-1α (HIF-1α) and inflammatory factors were measured, followed by analysis of relevant inflammatory pathways. Immunofluorescence and molecular biology methods were employed to assess osteoclast differentiation in RAW264.7 cells after nuclear factor-κB ligand (RANKL) induction. A rat model of periodontitis was es\lished using ligature wires, and alveolar bone loss was assessed via micro-computed tomography. Osteoclastogenesis and periodontal inflammation were assessed through immunohistochemistry as well as hematoxylin and eosin staining.Results: DFO reduced the P.g-LPS-induced inflammatory factor expression (P < 0.0001) and upregulated HIF-1α (P = 0.0278) in RAW264.7 cells. DFO suppressed NF-κB signaling by inhibiting NF-κB p65 nuclear translocation and phosphorylation. DFO pretreatment inhibited osteoclast development by decreasing F-actin rings synthesis, reducing the number of mature osteoclasts (P < 0.0001) and downregulating osteoclast-specific markers (P < 0.05). In rat periodontitis models, DFO treatment reduced tissue inflammation, osteoclastogenesis, and alveolar bone loss (P  < 0.05).Conclusion: DFO effectively prevented osteoclast development, alveolar bone loss, and inflammation associated with periodontitis.Keywords: deferoxamine, periodontitis, inflammation, osteoclast differentiation
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spelling doaj-art-cf4ea147974544d38d51edfa9d5a2a9f2024-11-26T17:58:43ZengDove Medical PressJournal of Inflammation Research1178-70312024-11-01Volume 179637965097667Deferoxamine Treatment Effectively Prevents Periodontitis Progression by Reducing Inflammation and Osteoclastogenesis in Experimental Periodontitis RatsZhu YQiao SPang YWang HZhou YYanlin Zhu,1,2 Shuwei Qiao,2,3 Yuxuan Pang,2,3 Huimin Wang,2,3 Yanmin Zhou1,2 1Department of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China; 2Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China; 3Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yanmin Zhou, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 1500 Qinghua Road, Changchun, Jilin Province, 130021, People’s Republic of China, Tel +8618943971001, Email zhouym@jlu.edu.cnPurpose: Although the anti-inflammatory properties of the hypoxia-mimetic drug deferoxamine (DFO) have been reported, its potential as a treatment for periodontitis remains unknown. This study investigated the therapeutic benefits of DFO on osteoclastogenesis and inflammation in periodontitis progression.Methods: RAW264.7 cells were pretreated with DFO before stimulation with lipopolysaccharides from Porphyromonas gingivalis (P.g-LPS). Hypoxia-inducible factor-1α (HIF-1α) and inflammatory factors were measured, followed by analysis of relevant inflammatory pathways. Immunofluorescence and molecular biology methods were employed to assess osteoclast differentiation in RAW264.7 cells after nuclear factor-κB ligand (RANKL) induction. A rat model of periodontitis was es\lished using ligature wires, and alveolar bone loss was assessed via micro-computed tomography. Osteoclastogenesis and periodontal inflammation were assessed through immunohistochemistry as well as hematoxylin and eosin staining.Results: DFO reduced the P.g-LPS-induced inflammatory factor expression (P < 0.0001) and upregulated HIF-1α (P = 0.0278) in RAW264.7 cells. DFO suppressed NF-κB signaling by inhibiting NF-κB p65 nuclear translocation and phosphorylation. DFO pretreatment inhibited osteoclast development by decreasing F-actin rings synthesis, reducing the number of mature osteoclasts (P < 0.0001) and downregulating osteoclast-specific markers (P < 0.05). In rat periodontitis models, DFO treatment reduced tissue inflammation, osteoclastogenesis, and alveolar bone loss (P  < 0.05).Conclusion: DFO effectively prevented osteoclast development, alveolar bone loss, and inflammation associated with periodontitis.Keywords: deferoxamine, periodontitis, inflammation, osteoclast differentiationhttps://www.dovepress.com/deferoxamine-treatment-effectively-prevents-periodontitis-progression--peer-reviewed-fulltext-article-JIRdeferoxamineperiodontitisinflammationosteoclast differentiation
spellingShingle Zhu Y
Qiao S
Pang Y
Wang H
Zhou Y
Deferoxamine Treatment Effectively Prevents Periodontitis Progression by Reducing Inflammation and Osteoclastogenesis in Experimental Periodontitis Rats
Journal of Inflammation Research
deferoxamine
periodontitis
inflammation
osteoclast differentiation
title Deferoxamine Treatment Effectively Prevents Periodontitis Progression by Reducing Inflammation and Osteoclastogenesis in Experimental Periodontitis Rats
title_full Deferoxamine Treatment Effectively Prevents Periodontitis Progression by Reducing Inflammation and Osteoclastogenesis in Experimental Periodontitis Rats
title_fullStr Deferoxamine Treatment Effectively Prevents Periodontitis Progression by Reducing Inflammation and Osteoclastogenesis in Experimental Periodontitis Rats
title_full_unstemmed Deferoxamine Treatment Effectively Prevents Periodontitis Progression by Reducing Inflammation and Osteoclastogenesis in Experimental Periodontitis Rats
title_short Deferoxamine Treatment Effectively Prevents Periodontitis Progression by Reducing Inflammation and Osteoclastogenesis in Experimental Periodontitis Rats
title_sort deferoxamine treatment effectively prevents periodontitis progression by reducing inflammation and osteoclastogenesis in experimental periodontitis rats
topic deferoxamine
periodontitis
inflammation
osteoclast differentiation
url https://www.dovepress.com/deferoxamine-treatment-effectively-prevents-periodontitis-progression--peer-reviewed-fulltext-article-JIR
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AT qiaos deferoxaminetreatmenteffectivelypreventsperiodontitisprogressionbyreducinginflammationandosteoclastogenesisinexperimentalperiodontitisrats
AT pangy deferoxaminetreatmenteffectivelypreventsperiodontitisprogressionbyreducinginflammationandosteoclastogenesisinexperimentalperiodontitisrats
AT wangh deferoxaminetreatmenteffectivelypreventsperiodontitisprogressionbyreducinginflammationandosteoclastogenesisinexperimentalperiodontitisrats
AT zhouy deferoxaminetreatmenteffectivelypreventsperiodontitisprogressionbyreducinginflammationandosteoclastogenesisinexperimentalperiodontitisrats