Next Article in Journal
Advances in Monitoring Cell-Based Therapies with Magnetic Resonance Imaging: Future Perspectives
Next Article in Special Issue
Gene Expression in Osteolysis: Review on the Identification of Altered Molecular Pathways in Preclinical and Clinical Studies
Previous Article in Journal
Neuroprotective Strategy in Retinal Degeneration: Suppressing ER Stress-Induced Cell Death via Inhibition of the mTOR Signal
Previous Article in Special Issue
Hydrostatic Pressure Regulates MicroRNA Expression Levels in Osteoarthritic Chondrocyte Cultures via the Wnt/β-Catenin Pathway
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(1), 203;

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

4,5,* and 1,2,*
The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands WA 6009, Australia
Orthopedic Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China
College of Chinese Materia Medical, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
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)
Full-Text   |   PDF [4999 KB, uploaded 19 January 2017]   |  


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

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top