A flavonoids compound inhibits osteoclast differentiation by attenuating RANKL induced NFATc-1/c-Fos induction

Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Ke Zhang, Jun Lei, Yuan He, Xiaobin Yang, Zhen Zhang, Dingjun Hao, Biao Wang, Baorong He
Function studies of pectolinarigenin demonstrated that, as a natural product, it possesses the regulatory effects on transcription factors (TFs) such as: signal transducer and activator of transcription 3 (STAT3). Herein, we aimed to identify the regulatroy effects of pectolinarigenin on the osteoclastogenesis TFs such as: NFATc1 and c-Fos, and further identify the relevant up-stream signals activity. We initially found pectolinarigenin inhibited receptor activator of nuclear factor-kappa B ligand (RANKL) induced osteoclast formation during the bone marrow-derived macrophages (BMMs) cultures, suggesting that this natural product could act on osteoclast precursors by inhibiting the down signaling cascades of RANKL signaling. Moreover, mechanistical investigation showed pectolinarigenin inhibits RANKL-mediated osteoclastogenesis by attenuating the nuclear factor of activated T cells cytoplasmic 1 (NFATc-1) and c-Fos following the Akt and mitogen activated protein kinases (MAPKs) signaling costimulatory. These findings identify that pectolinarigenin may act as an anti-resorption agent by blocking osteoclast activation.



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