Open AccessDehydrocostus lactone attenuates osteoclastogenesis and osteoclast‐induced bone loss by modulating NF‐κB signalling pathway
Author(s) -
Hu Bin,
Wu Fengfeng,
Shi Zhongli,
He Bin,
Zhao Xiang,
Wu Haobo,
Yan Shigui
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14492
Subject(s) - osteoclast , rankl , osteolysis , bone resorption , chemistry , nf κb , in vivo , cancer research , microbiology and biotechnology , pharmacology , activator (genetics) , medicine , endocrinology , in vitro , signal transduction , receptor , biochemistry , biology , dentistry
Osteolysis is characterized by overactivated osteoclast formation and potent bone resorption. It is enhanced in many osteoclast‐related diseases including osteoporosis and periprosthetic osteolysis. The shortage of effective treatments for these pathological processes emphasizes the importance of screening and identifying potential regimens that could attenuate the formation and function of osteoclasts. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone containing anti‐inflammatory properties. Here, we showed that DHE suppressed receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast formation and osteoclast marker gene expression. It also inhibited F‐actin ring formation and bone resorption in a dose‐dependent manner in vitro. Moreover, DHE inhibited the RANKL‐induced phosphorylation of NF‐κB, mitigated bone erosion in vivo in lipopolysaccharide‐induced inflammatory bone loss model and particle‐induced calvarial osteolysis model. Together, these results suggest that DHE reduces osteoclast‐related bone loss via the modulation of NF‐κB activation during osteoclastogenesis indicating that it might be a useful treatment for osteoclast‐related skeletal disorders.