title: Eriodictyol Inhibits RANKL-Induced Osteoclast Formation and Function Via Inhibition of NFATc1 Activity.
abstract: Receptor activator of nuclear factor kappa-B ligand (RANKL) induces differentiation and function of osteoclasts through triggering multiple signaling cascades, including NF-κB, MAPK, and Ca(2+) -dependent signals, which induce and activate critical transcription factor NFATc1. Targeting these signaling cascades may serve as an effective therapy against osteoclast-related diseases. Here, by screening a panel of natural plant extracts with known anti-inflammatory, anti-tumor, or anti-oxidant properties for possible anti-osteoclastogenic activities we identified Eriodictyol. This flavanone potently suppressed RANKL-induced osteoclastogenesis and bone resorption in a dose-dependent manner without detectable cytotoxicity, suppressing RANKL-induced NF-κB, MAPK, and Ca(2+) signaling pathways. Eriodictyol also strongly inhibited RANKL-induction of c-Fos levels (a critical component of AP-1 transcription factor required by osteoclasts) and subsequent activation of NFATc1, concomitant with reduced expression of osteoclast specific genes including cathepsin K (Ctsk), V-ATPase-d2 subunit, and tartrate resistant acid phosphatase (TRAcP/Acp5). Taken together, these data provide evidence that Eriodictyol could be useful for the prevention and treatment of osteolytic disorders associated with abnormally increased osteoclast formation and function. J. Cell. Physiol. 231: 1983-1993, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Biological Molecular Medicine Research of Guangxi Higher Education, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.|School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.|Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Fangming
authors.initials: F
authors.lastname: Song
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Biological Molecular Medicine Research of Guangxi Higher Education, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.|Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Biological Molecular Medicine Research of Guangxi Higher Education, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.|Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Mingli
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Functional Biomolecules, Medical School, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Renxiang
authors.initials: R
authors.lastname: Tan
authors.affiliation: Research Center for Drug Discovery (RCDD), School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: The Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
authors.forename: Julian M W
authors.initials: JM
authors.lastname: Quinn
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tickner
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Biological Molecular Medicine Research of Guangxi Higher Education, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.|Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Yuanjiao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Biological Molecular Medicine Research of Guangxi Higher Education, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.|School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D044950:Flavanones / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D044950:Flavanones; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; C007619:eriodictyol; C028610:flavanone