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Tetrahydroxystilbene Glucoside Regulates Proliferation, Differentiation, and OPG/RANKL/M-CSF Expression in MC3T3-E1 Cells via the PI3K/Akt Pathway
Open AccessArticle

l-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway

1
Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90110, Thailand
2
Department of Oral biology and Occlusion, Faculty of Dentistry, Prince of Songkla University, Hat-Yai, Songkhla 90110, Thailand
3
Department of Biomedical Science, University of Sheffield, Sheffield, England S10 2TN, UK
4
Center of Excellence in Natural Rubber Latex Biotechnology Research and Development, Prince of Songkla University, Hat-Yai, Songkhla 90110, Thailand
*
Author to whom correspondence should be addressed.
Academic Editors: Atanas G. Atanasov, Karel Šmejkal and Elke Heiss
Molecules 2018, 23(12), 3086; https://doi.org/10.3390/molecules23123086
Received: 22 October 2018 / Revised: 20 November 2018 / Accepted: 21 November 2018 / Published: 26 November 2018
(This article belongs to the Special Issue Bioactive Molecules and Their Mechanisms of Action)
Osteoporosis is widely recognized as a major health problem caused by an inappropriate rate of bone resorption compared to bone formation. Previously we showed that d-pinitol inhibits osteoclastogenesis but has no effect on osteoblastogenesis. However, the effect on osteoblast differentiation of its isomer, l-quebrachitol, has not yet been reported. The purpose of this study was, therefore, to investigate whether l-quebrachitol promotes the osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. Moreover, the molecular mechanism of action of l-quebrachitol was further explored. Here, it is shown for the first time that l-quebrachitol significantly promotes proliferation and cell DNA synthesis. It also enhances mineralization accompanied by increases in mRNA expression of bone matrix proteins including alkaline phosphatase (ALP), collagen type I (ColI), osteocalcin (OCN), and osteopontin (OPN). In addition, l-quebrachitol upregulates the mRNA and protein expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2), while down-regulating the receptor activator of the nuclear factor-κB ligand (RANKL) mRNA level. Moreover, the expression of regulatory genes associated with the mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/β-catenin signaling pathways are also upregulated. These findings indicate that l-quebrachitol may promote osteoblastogenesis by triggering the BMP-2-response as well as the Runx2, MAPK, and Wnt/β-catenin signaling pathway. View Full-Text
Keywords: l-quebrachitol; Osteoblastogenesis; Wnt/β-Catenin; BMP-2; Runx2; MAPK l-quebrachitol; Osteoblastogenesis; Wnt/β-Catenin; BMP-2; Runx2; MAPK
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Yodthong, T.; Kedjarune-Leggat, U.; Smythe, C.; Wititsuwannakul, R.; Pitakpornpreecha, T. l-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway. Molecules 2018, 23, 3086.

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