Unknown

Dataset Information

0

Poncirin Inhibits Osteoclast Differentiation and Bone Loss through Down-Regulation of NFATc1 In Vitro and In Vivo.


ABSTRACT: Activation of osteoclast and inactivation of osteoblast result in loss of bone mass with bone resorption, leading to the pathological progression of osteoporosis. The receptor activator of NF-?B ligand (RANKL) is a member of the TNF superfamily, and is a key mediator of osteoclast differentiation. A flavanone glycoside isolated from the fruit of Poncirus trifoliata, poncirin has anti-allergic, hypocholesterolemic, anti-inflammatory and anti-platelet activities. The present study investigates the effect of poncirin on osteoclast differentiation of RANKL-stimulated RAW264.7 cells. We observed reduced formation of RANKL-stimulated TRAP-positive multinucleated cells (a morphological feature of osteoclasts) after poncirin exposure. Real-time qPCR analysis showed suppression of the RANKL-mediated induction of key osteoclastogenic molecules such as NFATc1, TRAP, c-Fos, MMP9 and cathepsin K after poncirin treatment. Poncirin also inhibited the RANKL-mediated activation of NF-?B and, notably, JNK, without changes in ERK and p38 expression in RAW264.7 cells. Furthermore, we assessed the in vivo efficacy of poncirin in the lipopolysaccharide (LPS)-induced bone erosion model. Evaluating the micro-CT of femurs revealed that bone erosion in poncirin treated mice was markedly attenuated. Our results indicate that poncirin exerts anti-osteoclastic effects in vitro and in vivo by suppressing osteoclast differentiation. We believe that poncirin is a promising candidate for inflammatory bone loss therapeutics.

SUBMITTER: Chun KH 

PROVIDER: S-EPMC7327144 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Poncirin Inhibits Osteoclast Differentiation and Bone Loss through Down-Regulation of NFATc1 <i>In Vitro</i> and <i>In Vivo</i>.

Chun Kwang-Hoon KH   Jin Hyun Chul HC   Kang Ki Sung KS   Chang Tong-Shin TS   Hwang Gwi Seo GS  

Biomolecules & therapeutics 20200701 4


Activation of osteoclast and inactivation of osteoblast result in loss of bone mass with bone resorption, leading to the pathological progression of osteoporosis. The receptor activator of NF-κB ligand (RANKL) is a member of the TNF superfamily, and is a key mediator of osteoclast differentiation. A flavanone glycoside isolated from the fruit of <i>Poncirus trifoliata</i>, poncirin has anti-allergic, hypocholesterolemic, anti-inflammatory and anti-platelet activities. The present study investiga  ...[more]

Similar Datasets

| S-EPMC5099608 | biostudies-literature
| S-EPMC8895597 | biostudies-literature
| S-EPMC4471279 | biostudies-literature
| S-EPMC6167898 | biostudies-literature
| S-EPMC6240466 | biostudies-literature
| S-EPMC3851046 | biostudies-literature
| S-EPMC5461233 | biostudies-literature
| S-EPMC2919108 | biostudies-literature
| S-EPMC7076887 | biostudies-literature
| S-EPMC10822776 | biostudies-literature