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Eriodictyol Inhibits RANKL‐Induced Osteoclast Formation and Function Via Inhibition of NFATc1 Activity
Author(s) -
Song Fangming,
Zhou Lin,
Zhao Jinmin,
Liu Qian,
Yang Mingli,
Tan Renxiang,
Xu Jun,
Zhang Ge,
Quinn Julian M.W.,
Tickner Jennifer,
Huang Yuanjiao,
Xu Jiake
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25304
Subject(s) - eriodictyol , osteoclast , rankl , chemistry , function (biology) , microbiology and biotechnology , gain of function , biochemistry , biology , mutant , in vitro , receptor , activator (genetics) , luteolin , gene , antioxidant , quercetin
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.