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

• Main Authors: Zhu Y (Author), Qiao S (Author), Pang Y (Author), Wang H (Author), Zhou Y (Author)
• Format: Book
• Published: Dove Medical Press, 2024-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1178-7031
• Keywords: deferoxamine; periodontitis; inflammation; osteoclast differentiation; Pathology; RB1-214; Therapeutics. Pharmacology; RM1-950
• Source: Journal of Inflammation Research, Vol Volume 17, Pp 9637-9650 (2024)

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 [phone], Email [e-mail]: 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