The Coffee Diterpene Kahweol Prevents Osteoclastogenesis via Impairment of NFATc1 Expression and Blocking of Erk Phosphorylation

DOI Web Site PubMed 被引用文献6件 参考文献49件
  • Fumimoto Reiko
    Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan
  • Sakai Eiko
    Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan
  • Yamaguchi Yu
    Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan
  • Sakamoto Hiroshi
    Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan
  • Fukuma Yutaka
    Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan
  • Nishishita Kazuhisa
    Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan
  • Okamoto Kuniaki
    Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan
  • Tsukuba Takayuki
    Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Japan

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Osteoclasts (OCLs) are multinucleated bone resorbing cells whose differentiation is regulated by receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). It is known that inflammatory cytokines and oxidative stress stimulate differentiation of OCLs. Here we evaluated the effects of kahweol, a coffee-specific diterpene, which has been reported to possess anti-oxidant and anti-inflammatory properties, on the differentiation of bone marrow–derived macrophages (BMMs) or murine monocytic cell line RAW-D cells into OCLs. Kahweol dose-dependently inhibited the formation of tartrate-resistant acid phosphatase staining–positive OCLs from both BMMs and RAW-D cells. In addition, kahweol prevented the bone resorbing activity of OCLs. Kahweol completely abolished RANKL-stimulated phosphorylation of extracellular signal-regulated kinase and impaired phosphorylation of Akt. Moreover, the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), a master regulator for OCL differentiation; and OCL markers transcriptionally regulated by NFATc1 such as Src and cathepsin K were down-regulated by kahweol treatment. As one of the molecular mechanisms for the inhibitory effects of kahweol, we also showed that kahweol up-regulated heme oxygenase-1 and inhibited high mobility group box 1 release. Thus, kahweol in coffee is a useful constituent for inhibition of OCL differentiation.

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