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Int. J. Mol. Sci. 2017, 18(1), 203; doi:10.3390/ijms18010203

Bajijiasu Abrogates Osteoclast Differentiation via the Suppression of RANKL Signaling Pathways through NF-κB and NFAT

1,2,3,†
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2,†
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4
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1,3
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1,3
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1,3
,
1,3
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4
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2
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4,5,* and 1,2,*
1
The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
2
School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands WA 6009, Australia
3
Orthopedic Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China
4
College of Chinese Materia Medical, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
5
Artepharm, Co., Ltd., Guangzhou 510000, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Cory J. Xian
Received: 29 November 2016 / Revised: 9 January 2017 / Accepted: 11 January 2017 / Published: 19 January 2017
(This article belongs to the Special Issue Advances in Bone and Cartilage Research)
View Full-Text   |   Download PDF [4999 KB, uploaded 19 January 2017]   |  

Abstract

Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-κB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu—a natural compound derived from Morinda officinalis F. C. How—has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear. In the present study, we found that Bajijiasu dose-dependently inhibited RANKL-induced osteoclast formation and bone resorption from 0.1 mM, and reached half maximal inhibitory effects (IC50) at 0.4 mM without toxicity. Expression of RANKL-induced osteoclast specific marker genes including cathepsin K (Ctsk), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP), vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2), and (matrix metalloproteinase-2 (MMP2) was inhibited by Bajijiasu treatment. Luciferase reporter gene studies showed that Bajijiasu could significantly reduce the expression and transcriptional activity of NFAT as well as RANKL-induced NF-κB activation in a dose-dependent manner. Further, Bajijiasu was found to decrease the RANKL-induced phosphorylation of extracellular signal-regulated kinases (ERK), inhibitor of κB-α (IκB-α), NFAT, and V-ATPase d2. Taken together, this study revealed Bajijiasu could attenuate osteoclast formation and bone resorption by mediating RANKL signaling pathways, indicative of a potential effect of Bajijiasu on osteolytic bone diseases. View Full-Text
Keywords: Bajijiasu; osteoclast; RANKL; NF-κB; NFAT pathway Bajijiasu; osteoclast; RANKL; NF-κB; NFAT pathway
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MDPI and ACS Style

Hong, G.; Zhou, L.; Shi, X.; He, W.; Wang, H.; Wei, Q.; Chen, P.; Qi, L.; Tickner, J.; Lin, L.; Xu, J. Bajijiasu Abrogates Osteoclast Differentiation via the Suppression of RANKL Signaling Pathways through NF-κB and NFAT. Int. J. Mol. Sci. 2017, 18, 203.

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