Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by <i>Porphyromonas gingivalis</i> Lipopolysaccharide
The macrolide erythromycin (ERM) inhibits excessive neutrophil accumulation and bone resorption in inflammatory tissues. We previously reported that the expression of developmental endothelial locus-1 (DEL-1), an endogenous anti-inflammatory factor induced by ERM, is involved in ERM action. Furtherm...
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MDPI AG
2023-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/303 |
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| author | Hikaru Tamura Tomoki Maekawa Hisanori Domon Kridtapat Sirisereephap Toshihito Isono Satoru Hirayama Takumi Hiyoshi Karin Sasagawa Fumio Takizawa Takeyasu Maeda Yutaka Terao Koichi Tabeta |
| author_facet | Hikaru Tamura Tomoki Maekawa Hisanori Domon Kridtapat Sirisereephap Toshihito Isono Satoru Hirayama Takumi Hiyoshi Karin Sasagawa Fumio Takizawa Takeyasu Maeda Yutaka Terao Koichi Tabeta |
| author_sort | Hikaru Tamura |
| collection | DOAJ |
| description | The macrolide erythromycin (ERM) inhibits excessive neutrophil accumulation and bone resorption in inflammatory tissues. We previously reported that the expression of developmental endothelial locus-1 (DEL-1), an endogenous anti-inflammatory factor induced by ERM, is involved in ERM action. Furthermore, DEL-1 is involved in the induction of bone regeneration. Therefore, in this study, we investigated whether ERM exerts an osteoblastogenic effect by upregulating DEL-1 under inflammatory conditions. We performed in vitro cell-based mechanistic analyses and used a model of <i>Porphyromonas gingivalis</i> lipopolysaccharide (LPS)-induced periodontitis to evaluate how ERM restores osteoblast activity. In vitro, <i>P. gingivalis</i> LPS stimulation suppressed osteoblast differentiation and bone formation. However, ERM treatment combined with <i>P. gingivalis</i> LPS stimulation upregulated osteoblast differentiation-related factors and <i>Del1</i>, indicating that osteoblast differentiation was restored. Alveolar bone resorption and gene expression were evaluated in a periodontitis model, and the results confirmed that ERM treatment increased DEL-1 expression and suppressed bone loss by increasing the expression of osteoblast-associated factors. In conclusion, ERM restores bone metabolism homeostasis in inflammatory environments possibly via the induction of DEL-1. |
| first_indexed | 2024-03-11T08:18:26Z |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T08:18:26Z |
| publishDate | 2023-02-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-eb3da03291af4e20b0ae1cb1bcca8b3e2023-11-16T22:37:47ZengMDPI AGPharmaceuticals1424-82472023-02-0116230310.3390/ph16020303Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by <i>Porphyromonas gingivalis</i> LipopolysaccharideHikaru Tamura0Tomoki Maekawa1Hisanori Domon2Kridtapat Sirisereephap3Toshihito Isono4Satoru Hirayama5Takumi Hiyoshi6Karin Sasagawa7Fumio Takizawa8Takeyasu Maeda9Yutaka Terao10Koichi Tabeta11Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Periodontology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanCenter for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Periodontology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanThe macrolide erythromycin (ERM) inhibits excessive neutrophil accumulation and bone resorption in inflammatory tissues. We previously reported that the expression of developmental endothelial locus-1 (DEL-1), an endogenous anti-inflammatory factor induced by ERM, is involved in ERM action. Furthermore, DEL-1 is involved in the induction of bone regeneration. Therefore, in this study, we investigated whether ERM exerts an osteoblastogenic effect by upregulating DEL-1 under inflammatory conditions. We performed in vitro cell-based mechanistic analyses and used a model of <i>Porphyromonas gingivalis</i> lipopolysaccharide (LPS)-induced periodontitis to evaluate how ERM restores osteoblast activity. In vitro, <i>P. gingivalis</i> LPS stimulation suppressed osteoblast differentiation and bone formation. However, ERM treatment combined with <i>P. gingivalis</i> LPS stimulation upregulated osteoblast differentiation-related factors and <i>Del1</i>, indicating that osteoblast differentiation was restored. Alveolar bone resorption and gene expression were evaluated in a periodontitis model, and the results confirmed that ERM treatment increased DEL-1 expression and suppressed bone loss by increasing the expression of osteoblast-associated factors. In conclusion, ERM restores bone metabolism homeostasis in inflammatory environments possibly via the induction of DEL-1.https://www.mdpi.com/1424-8247/16/2/303macrolidesperiodontitis<i>Porphyromonas gingivalis</i> lipopolysaccharideosteoblastogenesisdevelopmental endothelial locus-1 |
| spellingShingle | Hikaru Tamura Tomoki Maekawa Hisanori Domon Kridtapat Sirisereephap Toshihito Isono Satoru Hirayama Takumi Hiyoshi Karin Sasagawa Fumio Takizawa Takeyasu Maeda Yutaka Terao Koichi Tabeta Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by <i>Porphyromonas gingivalis</i> Lipopolysaccharide Pharmaceuticals macrolides periodontitis <i>Porphyromonas gingivalis</i> lipopolysaccharide osteoblastogenesis developmental endothelial locus-1 |
| title | Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by <i>Porphyromonas gingivalis</i> Lipopolysaccharide |
| title_full | Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by <i>Porphyromonas gingivalis</i> Lipopolysaccharide |
| title_fullStr | Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by <i>Porphyromonas gingivalis</i> Lipopolysaccharide |
| title_full_unstemmed | Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by <i>Porphyromonas gingivalis</i> Lipopolysaccharide |
| title_short | Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by <i>Porphyromonas gingivalis</i> Lipopolysaccharide |
| title_sort | erythromycin restores osteoblast differentiation and osteogenesis suppressed by i porphyromonas gingivalis i lipopolysaccharide |
| topic | macrolides periodontitis <i>Porphyromonas gingivalis</i> lipopolysaccharide osteoblastogenesis developmental endothelial locus-1 |
| url | https://www.mdpi.com/1424-8247/16/2/303 |
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