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[논문] Fisetin promotes osteoblast differentiation and osteogenesis through GSK-3β phosphorylation at Ser9 and consequent β-catenin activation, inhibiting osteoporosis

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논문제목(Title)

[논문] Fisetin promotes osteoblast differentiation and osteogenesis through GSK-3β phosphorylation at Ser9 and consequent β-catenin activation, inhibiting osteoporosis

학술지명(Journal)

Biochemical Pharmacology

ImpactFactor

5.858

ISSN_ISBN

0006-2952

학술지볼륨권호(Volume)

192

SCI구분

SCIE

초록(Abstract)

Fisetin is a bioactive flavonol that inhibits osteoclastogenesis and promotes osteoblastogenesis. However, the osteogenic activity of fisetin needs to be comprehensively elucidated. In the present study, we observed that fisetin significantly increased alkaline phosphatase (ALP) activity and bone mineralization in MC3T3-E1 preosteoblasts, accompanied by a significant increase in runt-related transcription factor 2 (RUNX2), ALP, collagen type Ⅰ alpha 1 (Col1α1), osterix (OSX), osteocalcin (OCN), and bone morphogenetic protein 4 (BMP4) expression. Furthermore, fisetin promoted vertebral formation in zebrafish larvae, with the highest fisetin concentration comparable with that observed in β-glycerophosphate treatment. Fisetin also inhibited prednisolone (PDS)-induced anti-osteoblastic genes, including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase-6 (ACP6), dendritic cell-specific transmembrane protein (DC-STAMP), and cathepsin K (CTSK). Fisetin potently mitigated the PDS-induced inhibition of ALP activity and bone mineralization, as well as vertebral resorption in zebrafish larvae. Moreover, we confirmed that fisetin-induced osteogenic effect was activated through phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9, consequently releasing β-catenin from the destructive complex to promote its nuclear translocation. β-Catenin inhibition by FH535 and the stabilization of GSK-3β by DOI hydrochloride remarkably inhibited fisetin-induced osteogenic activities, indicating that the GSK-3β/β-catenin signaling pathway plays a vital role in fisetin-induced osteogenesis. Collectively, our findings suggest that fisetin stimulates osteogenic activity and could be used as an effective strategy to prevent bone resorption.

저자명(Author)

Molagoda, Ilandarage Menu Neelaka; Kang, Chang-Hee; Lee, Mi-Hwa; Choi, Yung Hyun; Lee, Chang-Min; Lee, Seungheon; Kim, Gi-Young;

학술지출판일자(PublicationDate)

2021.07.10.

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공개 일자

2024-09-03

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[김기영] 미세플라스틱(비스페놀A)의 면역시스템 교란에 미치는 영향(2019-2021)
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2024-09-03
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  • Version 1 2024-08-22
Cite as
Molagoda, Ilandarage Menu Neelaka; Kang, Chang-Hee; Lee, Mi-Hwa; Choi, Yung Hyun; Lee, Chang-Min; Lee, Seungheon; Kim, Gi-Young;, 2021.07.10., [논문] Fisetin promotes osteoblast differentiation and osteogenesis through GSK-3β phosphorylation at Ser9 and consequent β-catenin activation, inhibiting osteoporosis
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