JOURNAL ARTICLE

Licorice isoliquiritigenin suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo

Lingxin Zhu, Hongxia Wei, Yan Wu, Shasha Yang, Lan Xiao, Jie Zhang, Bin Peng
International Journal of Biochemistry & Cell Biology 2012, 44 (7): 1139-52
22521613
Osteoclasts, bone-specialized multinucleated cells, are responsible for bone destructive diseases such as osteoporosis, periodontitis, and rheumatoid arthritis. Natural plant-derived products have received substantial attention given their potential therapeutic and preventive activities against human diseases. In the present study, we investigated the effects of isoliquiritigenin (ISL), a natural flavonoid isolated from licorice, on receptor activator of nuclear factor-κB ligand (RANKL)-induced in vitro osteoclastogenesis and inflammation-mediated bone destruction in vivo. We observed that ISL dose-dependently inhibited RANKL-induced osteoclast formation from RAW 264.7 and primary mouse bone marrow-derived macrophages (BMMs), as well as decreased the extent of lacunar resorption. Specifically, ISL targeted RANKL-induced osteoclastogenesis and F-actin rings formation at an early stage. The RANKL-stimulated mRNA expression of osteoclast-related genes and transcription factors were also diminished by ISL. Mechanistically, ISL blocked the RANKL-triggered RANK-TRAF6 association, phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of κBα (IκBα) phosphorylation and degradation, nuclear factor-κB (NF-κB) p65 nuclear translocation, as well as activator protein (AP)-1 activation. ISL almost abrogated the nuclear factor of activated T cells (NFATc1) expression and inhibited its nuclear translocation specifically in pre-osteoclasts. Furthermore, the ectopic introduction of NFATc1 into osteoclast precursors almost reversed the ISL-elicited anti-osteoclastogenic effects. Consistent with the in vitro results, administration of ISL prevented inflammatory bone loss in mice by attenuating osteoclast activity. Taken together, our results demonstrated that ISL suppresses RANKL-induced osteoclastogenesis and inflammatory bone loss via RANK-TRAF6, MAPK, IκBα/NF-κB, and AP-1 signaling pathways. Therefore, ISL may be considered as a novel therapeutic and/or preventive strategy against lytic bone diseases.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
22521613
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"