Poncirin Inhibits Osteoclast Differentiation and Bone Loss through Down-Regulation of NFATc1 In Vitro and In Vivo
10.4062/biomolther.2018.216
- Author:
Kwang-Hoon CHUN
1
;
Hyun Chul JIN
;
Ki Sung KANG
;
Tong-Shin CHANG
;
Gwi Seo HWANG
Author Information
1. Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2020;28(4):337-343
- CountryRepublic of Korea
- Language:0
-
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-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 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-κB 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.
