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- W4327692902 abstract "Gnathodiaphyseal dysplasia (GDD; OMIM#166260) is a rare skeletal genetic disorder characterized by sclerosis of tubular bones and cemento-osseous lesions in mandibles. TMEM16E/ANO5 gene mutations have been identified in patients with GDD. Here, Ano5 knockout (Ano5-/- ) mice with enhanced osteoblastogenesis were used to investigate whether Ano5 disruption affects osteoclastogenesis.The maturation of osteoclasts, formation of F-actin ring and bone resorption were detected by immunohistochemistry, TRAP, phalloidin staining and Coming Osteo assays. The expression of osteoclast-related factors was measured by qRT-PCR. Early signaling pathways were verified by western blot.Ano5-/- mice exhibited inhibitory formation of multinucleated osteoclasts with a reduction of TRAP activity. The expression of Nfatc1, c-Fos, Trap, Ctsk, Mmp9, Rank and Dc-stamp was significantly decreased in bone tissues and bone marrow-derived macrophages (BMMs) of Ano5-/- mice. Ano5-/- osteoclasts manifested disrupted actin ring and less mineral resorption. RANKL-induced early signaling pathways were suppressed in Ano5-/- osteoclasts and Ano5 knockdown RAW264.7 cells. Moreover, the inhibitory effects of NF-κB signalling pathway on osteoclastogenesis were partially attenuated with NF-κB signalling activator.Ano5 deficiency impairs osteoclastogenesis, which leads to enhanced osteogenic phenotypes mediated by bone homeostasis dysregulation." @default.
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- W4327692902 date "2023-03-29" @default.
- W4327692902 modified "2023-09-23" @default.
- W4327692902 title "Genetic disruption of <i>Ano5</i> leads to impaired osteoclastogenesis for gnathodiaphyseal dysplasia" @default.
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- W4327692902 doi "https://doi.org/10.1111/odi.14562" @default.
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