Referenced in: none

Automatically associated channels: ClC4 , ClC7

Title: Xanthohumol modulates the expression of osteoclast-specific genes during osteoclastogenesis in RAW264.7 cells.

Authors: Kwang Sik Suh, Sang Youl Rhee, Young Seol Kim, Young Soon Lee, Eun Mi Choi

Journal, date & volume: Food Chem. Toxicol., 2013 Dec , 62, 99-106

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23994090

Abstract
RANKL has been shown to play a critical role in osteoclast formation and bone resorption. Thus, agents that suppress RANKL signaling have a potential to suppress bone loss. In this study, we examined the ability of xanthohumol, a structurally simple prenylated chalcone, to suppress RANKL signaling during osteoclastogenesis in RAW264.7 cells. Xanthohumol markedly inhibited RANKL-induced TRAP activity, multinucleated osteoclasts formation, and resorption-pit formation. In experiments to elucidate its mechanism of action, xanthohumol was found to suppress RANKL-induced expression of TRAF6, GAB2, ERK, c-Src, PI3K, and Akt genes. Moreover, RANKL-induced expressions of c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis, were reduced by treatment with xanthohumol. Xanthohumol also inhibited RANKL-induced expression of bone-resorption related osteoclast-specific genes (carbonic anhydrase II, TCIRG, CLCN7, OSTM1, cathepsin K, and MMP-9). These data demonstrate that xanthohumol inhibits osteoclastogenesis by modulating RANKL signaling and may be useful for the prevention of bone-destructive diseases such as osteoporosis, arthritis and periodontitis.