The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation.

Autor:	Sakaida K; Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan., Omori K; Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan., Nakayama M; Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan., Mandai H; Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science, Gifu, Japan., Nakagawa S; Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan., Sako H; Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan., Kamei C; Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan., Yamamoto S; Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan., Kobayashi H; Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan., Ishii S; Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University, Okayama, Japan., Ono M; Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan., Ibaragi S; Department of Oral Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan., Yamashiro K; Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan., Yamamoto T; Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan., Suga S; Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University, Okayama, Japan., Takashiba S; Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2021 Jun 08; Vol. 12, pp. 674366. Date of Electronic Publication: 2021 Jun 08 (Print Publication: 2021).
DOI:	10.3389/fphar.2021.674366
Abstrakt:	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-κB 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 PKCα/βII, 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Sakaida, Omori, Nakayama, Mandai, Nakagawa, Sako, Kamei, Yamamoto, Kobayashi, Ishii, Ono, Ibaragi, Yamashiro, Yamamoto, Suga and Takashiba.)
Databáze:	MEDLINE
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