期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 18, 期 1, 页码 -出版社
MDPI AG
DOI: 10.3390/ijms18010203
关键词
Bajijiasu; osteoclast; RANKL; NF-kappa B; NFAT pathway
资金
- Australian Health and Medical Research Council (NHMRC) [APP1107828, APP1127396, APP1127156]
- Arthritis Foundation of Australia (The H J & G J Mckenzie grant)
- Western Australia Medical & Health Research Infrastructure Fund
- University of Western Australia Research Collaboration Awards
- National Natural Science Foundation of China [81473697]
- YangFan Innovative And Entrepreneurial Research Team Project [2014YT02S008]
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-kappa B 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-kappa B activation in a dose-dependent manner. Further, Bajijiasu was found to decrease the RANKL-induced phosphorylation of extracellular signal-regulated kinases (ERK), inhibitor of kappa B-alpha (I kappa B-alpha), 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.
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