miR-1260b inhibits periodontal bone loss by targeting ATF6β mediated regulation of ER stress
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- 林, 千華子
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 福田, 隆男
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 川上, 賢太郎
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 豊田, 真顕
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 中尾, 雄紀
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 渡邊, ゆかり
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 新城, 尊徳
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 佐野, 朋美
- 九州大学大学院歯学研究院口腔常態制御学口腔機能分子科学
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- 岩下, 未咲
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 四本, かれん
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 信太, 実有
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 武富, 孝治
- 久留米大学
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- 讃井, 彰一
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
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- 内海, 健
- 九州大学大学院医学研究院
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- 兼松, 隆
- 九州大学大学院歯学研究院口腔常態制御学口腔機能分子科学
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- 西村, 英紀
- 九州大学大学院歯学研究院口腔機能修復学歯周病学
説明
The expression profiles of exosomal microRNAs (miRNAs) are regulated by the microenvironment, and appropriate priming with mesenchymal stem cells (MSCs) is one of the strategies to enhance the paracrine potency of MSCs. Our previous work demonstrated that exosomes from tumor necrosis factor (TNF)-α-primed human gingiva-derived MSCs (GMSCs) could be a therapeutic tool against periodontitis, and that TNFα-inducible exosomal miR-1260b is essential for the inhibition of alveolar bone loss. However, the precise molecular mechanism underlying miR-1260b-mediated inhibition of osteoclastogenesis is not yet fully understood. Here, we found that the activating transcription factor (ATF)-6β, a novel miR-1260b-targeting gene, is critical for the regulation of osteoclastogenesis under endoplasmic reticulum (ER) stress. An experimental periodontal mouse model demonstrated that induction of ER stress was accompanied by enhanced ATF6β expression, and local administration of miR-1260b and ATF6β siRNA using polyethylenimine nanoparticles (PEI-NPs) significantly suppressed the periodontal bone resorption. In periodontal ligament (PDL) cells, the ER stress inducer, tunicamycin, enhanced the expression of the receptor activator of NF-κB ligand (RANKL), while miR-1260b-mediated downregulation of ATF6β caused RANKL inhibition. Furthermore, the secretome from miR-1260b/ATF6β-axis-activated PDL cells inhibited osteoclastogenesis in human CD14^+ peripheral blood-derived monocytes. These results indicate that the miR-1260b/ATF6β axis mediates the regulation of ER stress, which may be used as a novel therapeutic strategy to treat periodontal disease.
収録刊行物
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- Frontiers in Cell and Developmental Biology
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Frontiers in Cell and Developmental Biology 10 2022-11-30
Frontiers Media SA
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詳細情報 詳細情報について
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- CRID
- 1050018672316797824
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- ISSN
- 2296634X
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- HANDLE
- 2324/7177891
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- PubMed
- 36531939
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- Crossref
- KAKEN
- OpenAIRE