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- W3035676989 abstract "Abstract Long-term administration of nitrogen-containing bisphosphonates increases the risk of detrimental side effects, such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). BRONJ development is associated with inflammation, but its pathophysiology remains unknown. Here, we examined whether histone methylation is responsible for zoledronic acid (Zol)-induced inflammatory responses. We found that Kdm6a and Kdm6b markedly increased interleukin 1β expression and Gasdermin D cleavage, which are both activated by Caspase 1, in macrophages. Inhibitors of Kdm6a and Kdm6b robustly abolished Zol-enhanced interleukin 1β synthesis and secretion from macrophages. When Kdm6a and Kdm6b were pharmacologically inhibited in vivo, poor healing of the alveolar socket and inflammatory responses were ameliorated in Zol-treated mice. Taken together, we showed the pathologic role of Kdm6a and Kdm6b in Zol-promoted inflammatory responses and demonstrated that Kdm6a and Kdm6b are potential therapeutic targets for the treatment of BRONJ." @default.
- W3035676989 created "2020-06-19" @default.
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- W3035676989 date "2020-06-11" @default.
- W3035676989 modified "2023-10-15" @default.
- W3035676989 title "Zoledronic acid regulates the synthesis and secretion of IL-1β through Histone methylation in macrophages" @default.
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- W3035676989 doi "https://doi.org/10.1038/s41420-020-0273-4" @default.
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