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論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Necrostatin-7 suppresses RANK-NFATc1 signaling and attenuates macrophage to osteoclast differentiation
掲載誌名	正式名：Biochemical and biophysical research communications 略　 称：Biochem Biophys Res Commun ISSNコード：1090-2104(Electronic)0006-291X(Linking)
掲載区分	国外
巻・号・頁	503(2),pp.544-9
著者・共著者	Fuji Hiroaki, Ohmae Saori, Noma Naruto, Takeiri Masatoshi, Yasutomi Hideto, Izumi Kazuya, Ito Moe, Toyomoto Masayasu, Iwaki Soichiro, Takemoto Kenji, Seo Satoru, Taura Kojiro, Hida Shigeaki, Aoyama Mineyoshi, Ishihama Yasushi, Hagiwara Masatoshi, Takeda Norihiko, Hatano Etsuro, Iwaisako Keiko, Uemoto Shinji, Asagiri Masataka
発行年月	2018/09
概要	Osteoclasts play a crucial role in osteolytic bone diseases, such as osteoporosis, rheumatoid arthritis, periodontitis, Paget's disease of bone and bone metastatic tumors. Therefore, controlling osteoclast differentiation and function has been considered a promising therapeutic strategy. Here, we show that necrostatin (Nec)-7, an inhibitor of programmed necrosis, strongly suppressed receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption, without compromising macrophage colony-stimulating factor (M-CSF)-supported survival and growth of osteoclast precursor cells. Accordingly, Nec-7 significantly decreased the levels of RANKL-induced osteoclastogenic marker genes, such as cathepsin K. Mechanistically, Nec-7 neither affected MAPK nor NF-κB activation; however, it strongly inhibited the RANKL receptor (RANK) to nuclear factor of activated T cells c1 (NFATc1) signaling. Lentiviral expression of RANK in bone marrow-derived macrophages significantly restored osteoclastogenesis and NFATc1 amplification in Nec-7-treated cells. In this study, we revealed that Nec-7-sensitive pathways are crucially involved in osteoclast formation and function. Investigation of the molecular mechanism(s) through which Nec-7 inhibits RANK-NFATc1 signaling axis may lead to the development of new therapeutic strategies for bone disease.
DOI	10.1016/j.bbrc.2018.05.153
PMID	29800570