Browsing by Subject "organ inflammation"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Imatinib has minimal effects on inflammatory and osteopenic phenotypes in a murine cherubism model
    (Wiley, 2021) Mukai, Tomoyuki; Akagi, Takahiko; Hiramatsu Asano, Sumie; Tosa, Ikue; Ono, Mitsuaki; Kittaka, Mizuho; Ueki, Yasuyoshi; Yahagi, Ayano; Iseki, Masanori; Oohashi, Toshitaka; Ishihara, Katsuhiko; Morita, Yoshitaka; Biomedical Sciences and Comprehensive Care, School of Dentistry
    Objective Cherubism is a genetic disorder characterised by bilateral jawbone deformation. The associated jawbone lesions regress after puberty, whereas severe cases require surgical treatment. Although several drugs have been tested, fundamental treatment strategies for cherubism have not been established. The effectiveness of imatinib has recently been reported; however, its pharmaceutical mechanism remains unclear. In this study, we tested the effects of imatinib using a cherubism mouse model. Methods We used Sh3bp2 P416R cherubism mutant mice, which exhibit systemic organ inflammation and osteopenia. The effects of imatinib were determined using primary bone marrow-derived macrophages. Imatinib was administered intraperitoneally to the mice, and serum tumour necrosis factor-α (TNFα), organ inflammation and bone properties were examined. Results The cherubism mutant macrophages produced higher levels of TNFα in response to lipopolysaccharide compared to wild-type macrophages, and imatinib did not significantly suppress TNFα production. Although imatinib suppressed osteoclast formation in vitro, administering it in vivo did not suppress organ inflammation and osteopenia. Conclusion The in vivo administration of imatinib had a minimal therapeutic impact in cherubism mutant mice. To establish better pharmaceutical interventions, it is necessary to integrate new findings from murine models with clinical data from patients with a definitive diagnosis of cherubism.