ID | 62250 |
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Sakaida, Kyosuke
Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Omori, Kazuhiro
Department of Periodontics and Endodontics, Okayama University Hospital
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Nakayama, Masaaki
Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mandai, Hiroki
Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science
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Nakagawa, Saki
Department of Periodontics and Endodontics, Okayama University Hospital
Sako, Hidefumi
Department of Periodontics and Endodontics, Okayama University Hospital
Kamei, Chiaki
Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yamamoto, Satoshi
Department of Periodontics and Endodontics, Okayama University Hospital
Kobayashi, Hiroya
Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ishii, Satoki
Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University
Ono, Mitsuaki
Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Ibaragi, Soichiro
Department of Oral Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Yamashiro, Keisuke
Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan, 3Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Yamamoto, Tadashi
Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Suga, Seiji
Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University
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Takashiba, Shogo
Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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抄録 | Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKC alpha/beta II, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.
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キーワード | (+)-terrein
ovariectomy
osteoporosis
RANKL
PKC
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発行日 | 2021-06-08
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出版物タイトル |
Frontiers In Pharmacology
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巻 | 12巻
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出版者 | Frontiers Media SA
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開始ページ | 674366
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ISSN | 1663-9812
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2021 Sakaida, Omori, Nakayama, Mandai, Nakagawa, Sako, Kamei, Yamamoto, Kobayashi, Ishii, Ono, Ibaragi, Yamashiro, Yamamoto, Suga and Takashiba.
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論文のバージョン | publisher
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関連URL | isVersionOf https://doi.org/10.3389/fphar.2021.674366
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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助成機関名 |
日本学術振興会
Wesco Scientific Promotion Foundation
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助成番号 | 19K10108
20K18509
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