論文

査読有り 国際誌
2020年6月

The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1.

International immunopharmacology
  • Saki Nakagawa
  • ,
  • Kazuhiro Omori
  • ,
  • Masaaki Nakayama
  • ,
  • Hiroki Mandai
  • ,
  • Satoshi Yamamoto
  • ,
  • Hiroya Kobayashi
  • ,
  • Hidefumi Sako
  • ,
  • Kyosuke Sakaida
  • ,
  • Hiroshi Yoshimura
  • ,
  • Satoki Ishii
  • ,
  • Soichiro Ibaragi
  • ,
  • Kimito Hirai
  • ,
  • Keisuke Yamashiro
  • ,
  • Tadashi Yamamoto
  • ,
  • Seiji Suga
  • ,
  • Shogo Takashiba

83
開始ページ
106429
終了ページ
106429
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.intimp.2020.106429

Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.

リンク情報
DOI
https://doi.org/10.1016/j.intimp.2020.106429
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32222639
ID情報
  • DOI : 10.1016/j.intimp.2020.106429
  • PubMed ID : 32222639

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