Beta-Cryptoxanthin Inhibits Lipopolysaccharide-Induced Osteoclast Differentiation and Bone Resorption via the Suppression of Inhibitor of NF-κB Kinase Activity

Narumi Hirata, Ryota Ichimaru, Tsukasa Tominari, Chiho Matsumoto, Kenta Watanabe, Keita Taniguchi, Michiko Hirata, Sihui Ma, Katsuhiko Suzuki, Florian M.W. Grundler, Chisato Miyaura, Masaki Inada

研究成果: Article

2 引用 (Scopus)

抄録

Beta-cryptoxanthin (β-cry) is a typical carotenoid found abundantly in fruit and vegetables such as the Japanese mandarin orange, persimmon, papaya, paprika, and carrot, and exerts various biological activities (e.g., antioxidant effects). We previously reported that β-cry suppressed lipopolysaccharide (LPS)-induced osteoclast differentiation via the inhibition of prostaglandin (PG) E₂ production in gingival fibroblasts and restored the alveolar bone loss in a mouse model for periodontitis in vivo. In this study, we investigated the molecular mechanism underlying the inhibitory effects of β-cry on osteoclast differentiation. In mouse calvarial organ cultures, LPS-induced bone resorption was suppressed by β-cry. In osteoblasts, β-cry inhibited PGE₂ production via the downregulation of the LPS-induced mRNA expression of cyclooxygenase (COX)-2 and membrane-bound PGE synthase (mPGES)-1, which are PGE synthesis-related enzymes, leading to the suppression of receptor activator of NF-κB ligand (RANKL) mRNA transcriptional activation. In an in vitro assay, β-cry directly suppressed the activity of the inhibitor of NF-κB kinase (IKK) β, and adding ATP canceled this IKKβ inhibition. Molecular docking simulation further suggested that β-cry binds to the ATP-binding pocket of IKKβ. In Raw264.7 cells, β-cry suppressed RANKL-mediated osteoclastogenesis. The molecular mechanism underlying the involvement of β-cry in LPS-induced bone resorption may involve the ATP-competing inhibition of IKK activity, resulting in the suppression of NF-κB signaling.

元の言語English
ジャーナルNutrients
11
発行部数2
DOI
出版物ステータスPublished - 2019 2 10

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IKappaB kinase
beta-cryptoxanthin
osteoclasts
bone resorption
Osteoclasts
Bone Resorption
Prostaglandins E
lipopolysaccharides
Lipopolysaccharides
phosphotransferases (kinases)
Phosphotransferases
Adenosine Triphosphate
Molecular Docking Simulation
Diospyros
Alveolar Bone Loss
Carica
paprika
Capsicum
Messenger RNA
Daucus carota

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

これを引用

Beta-Cryptoxanthin Inhibits Lipopolysaccharide-Induced Osteoclast Differentiation and Bone Resorption via the Suppression of Inhibitor of NF-κB Kinase Activity. / Hirata, Narumi; Ichimaru, Ryota; Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Taniguchi, Keita; Hirata, Michiko; Ma, Sihui; Suzuki, Katsuhiko; Grundler, Florian M.W.; Miyaura, Chisato; Inada, Masaki.

:: Nutrients, 巻 11, 番号 2, 10.02.2019.

研究成果: Article

Hirata, N, Ichimaru, R, Tominari, T, Matsumoto, C, Watanabe, K, Taniguchi, K, Hirata, M, Ma, S, Suzuki, K, Grundler, FMW, Miyaura, C & Inada, M 2019, 'Beta-Cryptoxanthin Inhibits Lipopolysaccharide-Induced Osteoclast Differentiation and Bone Resorption via the Suppression of Inhibitor of NF-κB Kinase Activity', Nutrients, 巻. 11, 番号 2. https://doi.org/10.3390/nu11020368
Hirata, Narumi ; Ichimaru, Ryota ; Tominari, Tsukasa ; Matsumoto, Chiho ; Watanabe, Kenta ; Taniguchi, Keita ; Hirata, Michiko ; Ma, Sihui ; Suzuki, Katsuhiko ; Grundler, Florian M.W. ; Miyaura, Chisato ; Inada, Masaki. / Beta-Cryptoxanthin Inhibits Lipopolysaccharide-Induced Osteoclast Differentiation and Bone Resorption via the Suppression of Inhibitor of NF-κB Kinase Activity. :: Nutrients. 2019 ; 巻 11, 番号 2.
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abstract = "Beta-cryptoxanthin (β-cry) is a typical carotenoid found abundantly in fruit and vegetables such as the Japanese mandarin orange, persimmon, papaya, paprika, and carrot, and exerts various biological activities (e.g., antioxidant effects). We previously reported that β-cry suppressed lipopolysaccharide (LPS)-induced osteoclast differentiation via the inhibition of prostaglandin (PG) E₂ production in gingival fibroblasts and restored the alveolar bone loss in a mouse model for periodontitis in vivo. In this study, we investigated the molecular mechanism underlying the inhibitory effects of β-cry on osteoclast differentiation. In mouse calvarial organ cultures, LPS-induced bone resorption was suppressed by β-cry. In osteoblasts, β-cry inhibited PGE₂ production via the downregulation of the LPS-induced mRNA expression of cyclooxygenase (COX)-2 and membrane-bound PGE synthase (mPGES)-1, which are PGE synthesis-related enzymes, leading to the suppression of receptor activator of NF-κB ligand (RANKL) mRNA transcriptional activation. In an in vitro assay, β-cry directly suppressed the activity of the inhibitor of NF-κB kinase (IKK) β, and adding ATP canceled this IKKβ inhibition. Molecular docking simulation further suggested that β-cry binds to the ATP-binding pocket of IKKβ. In Raw264.7 cells, β-cry suppressed RANKL-mediated osteoclastogenesis. The molecular mechanism underlying the involvement of β-cry in LPS-induced bone resorption may involve the ATP-competing inhibition of IKK activity, resulting in the suppression of NF-κB signaling.",
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T1 - Beta-Cryptoxanthin Inhibits Lipopolysaccharide-Induced Osteoclast Differentiation and Bone Resorption via the Suppression of Inhibitor of NF-κB Kinase Activity

AU - Hirata, Narumi

AU - Ichimaru, Ryota

AU - Tominari, Tsukasa

AU - Matsumoto, Chiho

AU - Watanabe, Kenta

AU - Taniguchi, Keita

AU - Hirata, Michiko

AU - Ma, Sihui

AU - Suzuki, Katsuhiko

AU - Grundler, Florian M.W.

AU - Miyaura, Chisato

AU - Inada, Masaki

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N2 - Beta-cryptoxanthin (β-cry) is a typical carotenoid found abundantly in fruit and vegetables such as the Japanese mandarin orange, persimmon, papaya, paprika, and carrot, and exerts various biological activities (e.g., antioxidant effects). We previously reported that β-cry suppressed lipopolysaccharide (LPS)-induced osteoclast differentiation via the inhibition of prostaglandin (PG) E₂ production in gingival fibroblasts and restored the alveolar bone loss in a mouse model for periodontitis in vivo. In this study, we investigated the molecular mechanism underlying the inhibitory effects of β-cry on osteoclast differentiation. In mouse calvarial organ cultures, LPS-induced bone resorption was suppressed by β-cry. In osteoblasts, β-cry inhibited PGE₂ production via the downregulation of the LPS-induced mRNA expression of cyclooxygenase (COX)-2 and membrane-bound PGE synthase (mPGES)-1, which are PGE synthesis-related enzymes, leading to the suppression of receptor activator of NF-κB ligand (RANKL) mRNA transcriptional activation. In an in vitro assay, β-cry directly suppressed the activity of the inhibitor of NF-κB kinase (IKK) β, and adding ATP canceled this IKKβ inhibition. Molecular docking simulation further suggested that β-cry binds to the ATP-binding pocket of IKKβ. In Raw264.7 cells, β-cry suppressed RANKL-mediated osteoclastogenesis. The molecular mechanism underlying the involvement of β-cry in LPS-induced bone resorption may involve the ATP-competing inhibition of IKK activity, resulting in the suppression of NF-κB signaling.

AB - Beta-cryptoxanthin (β-cry) is a typical carotenoid found abundantly in fruit and vegetables such as the Japanese mandarin orange, persimmon, papaya, paprika, and carrot, and exerts various biological activities (e.g., antioxidant effects). We previously reported that β-cry suppressed lipopolysaccharide (LPS)-induced osteoclast differentiation via the inhibition of prostaglandin (PG) E₂ production in gingival fibroblasts and restored the alveolar bone loss in a mouse model for periodontitis in vivo. In this study, we investigated the molecular mechanism underlying the inhibitory effects of β-cry on osteoclast differentiation. In mouse calvarial organ cultures, LPS-induced bone resorption was suppressed by β-cry. In osteoblasts, β-cry inhibited PGE₂ production via the downregulation of the LPS-induced mRNA expression of cyclooxygenase (COX)-2 and membrane-bound PGE synthase (mPGES)-1, which are PGE synthesis-related enzymes, leading to the suppression of receptor activator of NF-κB ligand (RANKL) mRNA transcriptional activation. In an in vitro assay, β-cry directly suppressed the activity of the inhibitor of NF-κB kinase (IKK) β, and adding ATP canceled this IKKβ inhibition. Molecular docking simulation further suggested that β-cry binds to the ATP-binding pocket of IKKβ. In Raw264.7 cells, β-cry suppressed RANKL-mediated osteoclastogenesis. The molecular mechanism underlying the involvement of β-cry in LPS-induced bone resorption may involve the ATP-competing inhibition of IKK activity, resulting in the suppression of NF-κB signaling.

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KW - bone resorption

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KW - osteoclast differentiation

KW - periodontitis

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