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Molecules 2019, 24(2), 271; https://doi.org/10.3390/molecules24020271 (registering DOI)

Cajanolactone A from Cajanus cajan Promoted Osteoblast Differentiation in Human Bone Marrow Mesenchymal Stem Cells via Stimulating Wnt/LRP5/β-Catenin Signaling

1
Laboratory of Chinese Herbal Drug Discovery, Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China
2
The Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China
3
Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China
*
Authors to whom correspondence should be addressed.
Received: 17 December 2018 / Revised: 30 December 2018 / Accepted: 9 January 2019 / Published: 12 January 2019
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Abstract

Cajanolactone A (CLA) is a stilbenoid discovered by us from Cajanus cajan (L.) Millsp. In our study, CLA was found to promote osteoblast differentiation in human bone marrow mesenchymal stem cells (hBMSCs), as judged by increased cellular alkaline phosphatase activity and extracellular calcium deposits, and elevated protein expression of Runx2, collagen-1, bone morphogenetic protein-2, and osteopontin. Mechanistic studies revealed that hBMSCs undergoing osteoblast differentiation expressed upregulated mRNA levels of Wnt3a, Wnt10b, LRP5/6, Frizzled 4, β-catenin, Runx2, and Osterix from the early stage of differentiation, indicating the role of activated Wnt/β-catenin signaling pathway in osteoblast differentiation. Addition of CLA to the differentiation medium further increased the mRNA level of Wnt3a, Wnt10b, Frizzled 4, LRP5, and β-catenin, inferring that CLA worked by stimulating Wnt/LRP5/β-catenin signaling. Wnt inhibitor dickkopf-1 antagonized CLA-promoted osteoblastogenesis, indicating that CLA did not target the downstream of canonical Wnt signaling pathway. Treatment with CLA caused no changes in mRNA expression level, as well as protein secretion of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL), indicating that CLA did not affect the OPG/RANKL axis. Our results showed that CLA, which promoted osteoblast differentiation in hBMSCs, through activating Wnt/LRP5/β-catenin signaling transduction, is a promising anti-osteoporotic drug candidate. View Full-Text
Keywords: cajanolactone A; Cajanus cajan (L.) Millsp.; osteoblast differentiation; Wnt/β-catenin signaling pathway cajanolactone A; Cajanus cajan (L.) Millsp.; osteoblast differentiation; Wnt/β-catenin signaling pathway
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Liu, S.; Luo, Z.-H.; Ji, G.-M.; Guo, W.; Cai, J.-Z.; Fu, L.-C.; Zhou, J.; Hu, Y.-J.; Shen, X.-L. Cajanolactone A from Cajanus cajan Promoted Osteoblast Differentiation in Human Bone Marrow Mesenchymal Stem Cells via Stimulating Wnt/LRP5/β-Catenin Signaling. Molecules 2019, 24, 271.

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