Desoxyrhapontigenin inhibits RANKL‑induced osteoclast formation and prevents inflammation‑mediated bone loss

Tran,Phuong  Thao; Park,Dong‑Hwa; Kim,Okhwa; Kwon,Seung‑Hae; Min,Byung‑Sun; Lee,Jeong‑Hyung

doi:10.3892/ijmm.2018.3627

Desoxyrhapontigenin inhibits RANKL‑induced osteoclast formation and prevents inflammation‑mediated bone loss

Authors:
- Phuong Thao Tran
- Dong‑Hwa Park
- Okhwa Kim
- Seung‑Hae Kwon
- Byung‑Sun Min
- Jeong‑Hyung Lee
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Affiliations: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon‑Do 24341, Republic of Korea, College of Pharmacy, Catholic University of Daegu, Hayang, Gyeongbuk 38430, Republic of Korea, Division of Bio‑Imaging, Korea Basic Science Institute Chuncheon Center, Chuncheon, Gangwon‑Do 24341, Republic of Korea
Published online on: April 17, 2018 https://doi.org/10.3892/ijmm.2018.3627
Pages: 569-578

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Abstract

Desoxyrhapontigenin (DRG), a stilbene compound from Rheum undulatum, has been found to exhibit various pharmacological activities, however, its impact on osteoclast formation has not been investigated. The present study investigated the effect of DRG on receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclast differentiation in mouse bone marrow macrophages (BMMs) and inflammation‑induced bone loss in vivo. BMMs or RAW264.7 cells were treated with DRG, followed by an evaluation of cell viability, RANKL‑induced osteoclast differentiation, actin‑ring formation and resorption pits activity. The effects of DRG on the RANKL‑induced phosphorylation of MAPK and the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) and c‑Fos were evaluated using western blot analysis once the BMMs were exposed to RANKL and DRG. The expression levels of osteoclast marker genes were also evaluated using western blot analysis and reverse transcription‑quantitative polymerase chain reaction A lipopolysaccharide (LPS)‑induced murine bone loss model was used to evaluate the protective effect of DRG on inflammation‑induced bone‑loss. The results demonstrated that DRG suppressed the RANKL‑induced differentiation of BMMs into osteoclasts, osteoclast actin‑ring formation and bone resorption activity in a dose‑dependent manner. Furthermore, DRG significantly inhibited LPS‑induced bone loss in a mouse model. At the molecular level, DRG inhibited the RANKL‑induced activation of extracellular signal‑regulated kinase, the expression of c‑Fos, and the induction of NFATc1, a crucial transcription factor for osteoclast formation. DRG decreased the expression levels of osteoclast marker genes, including matrix metalloproteinase‑9, tartrate‑resistant acid phosphatase and cathepsin K. In conclusion, these findings suggested that DRG inhibited the differentiation of BMMs into mature osteoclasts by suppressing the RANKL‑induced activator protein‑1 and NFATc1 signaling pathways, and may be a potential candidate for treating and/or preventing osteoclast‑associated diseases, including osteoporosis.

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