IADR Abstract Archives
Erythromycin Suppresses Inflammatory Bone Loss Through Reinduction of DEL-1
Objectives: Macrolides are used to treat periodontitis because of their immunomodulatory effects. However, the underlying mechanism of their action remains unclear. DEL-1 has currently emerged as an important factor in homeostatic immunity and osteoclastogenesis. Specifically, DEL-1 is down-regulated in periodontitis tissues. Therefore, in the present study we investigated whether the anti-inflammatory effects of macrolides are mediated through upregulation of DEL-1 expression.
Methods: The effect of erythromycin on inflammatory bone loss in mouse periodontitis was examined using mouse tooth ligating model in wild type and DEL-1 knock out mouse. Macrolide antibiotic Josamycin and beta-lactam antibiotic penicillin were used as control. Briefly, periodontal bone loss was induced for 9 days by ligating maxillary second molar and leaving the contralateral tooth unligated (baseline control). The mice were injected intraperitoneal with the antibiotics once a day daily thereafter until the sacrifice day. 9 days after the ligation, we collected maxillary bone and measured alveolar bone level. Additionally, the biological effects of induced DEL-1 in mouse models were evaluated in qPCR and IHC. The number of neutrophil infiltrations to the palate gingiva was measured by FACS.
Results: In the tooth ligating model, erythromycin-treated group tend to restrain bone loss compared to the other groups. However, DEL-1 knockout mice treated with erythromycin exhibit no significant suppression of bone resorption. Furthermore, the number of osteoclasts in bone tissue sections was decreased by erythromycin treatment. Erythromycin-treated group, DEL-1 gene expression was significantly up-regulated, and DEL-1 protein was recovered and localized in periodontal ligament. In addition, erythromycin treatment inhibited the neutrophil infiltration to palatal gingiva.
Conclusions: These results indicated that ERM promotes the induction of DEL-1, which is essential for the immunomodulatory properties of macrolides.
Methods: The effect of erythromycin on inflammatory bone loss in mouse periodontitis was examined using mouse tooth ligating model in wild type and DEL-1 knock out mouse. Macrolide antibiotic Josamycin and beta-lactam antibiotic penicillin were used as control. Briefly, periodontal bone loss was induced for 9 days by ligating maxillary second molar and leaving the contralateral tooth unligated (baseline control). The mice were injected intraperitoneal with the antibiotics once a day daily thereafter until the sacrifice day. 9 days after the ligation, we collected maxillary bone and measured alveolar bone level. Additionally, the biological effects of induced DEL-1 in mouse models were evaluated in qPCR and IHC. The number of neutrophil infiltrations to the palate gingiva was measured by FACS.
Results: In the tooth ligating model, erythromycin-treated group tend to restrain bone loss compared to the other groups. However, DEL-1 knockout mice treated with erythromycin exhibit no significant suppression of bone resorption. Furthermore, the number of osteoclasts in bone tissue sections was decreased by erythromycin treatment. Erythromycin-treated group, DEL-1 gene expression was significantly up-regulated, and DEL-1 protein was recovered and localized in periodontal ligament. In addition, erythromycin treatment inhibited the neutrophil infiltration to palatal gingiva.
Conclusions: These results indicated that ERM promotes the induction of DEL-1, which is essential for the immunomodulatory properties of macrolides.
