論文

査読有り 国際誌
2018年9月5日

Necrostatin-7 suppresses RANK-NFATc1 signaling and attenuates macrophage to osteoclast differentiation.

Biochemical and biophysical research communications
  • Hiroaki Fuji
  • ,
  • Saori Ohmae
  • ,
  • Naruto Noma
  • ,
  • Masatoshi Takeiri
  • ,
  • Hideto Yasutomi
  • ,
  • Kazuya Izumi
  • ,
  • Moe Ito
  • ,
  • Masayasu Toyomoto
  • ,
  • Soichiro Iwaki
  • ,
  • Kenji Takemoto
  • ,
  • Satoru Seo
  • ,
  • Kojiro Taura
  • ,
  • Shigeaki Hida
  • ,
  • Mineyoshi Aoyama
  • ,
  • Yasushi Ishihama
  • ,
  • Masatoshi Hagiwara
  • ,
  • Norihiko Takeda
  • ,
  • Etsuro Hatano
  • ,
  • Keiko Iwaisako
  • ,
  • Shinji Uemoto
  • ,
  • Masataka Asagiri

503
2
開始ページ
544
終了ページ
549
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2018.05.153

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.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2018.05.153
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29800570
ID情報
  • DOI : 10.1016/j.bbrc.2018.05.153
  • PubMed ID : 29800570

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