Poncirin Inhibits Osteoclast Differentiation and Bone Loss Through Down-Regulation of NFATc1 In Vitro and In Vivo
Kwang-Hoon Chun1, Hyun Chul Jin2, Ki Sung Kang2, Tong-Shin Chang3 and Gwi Seo Hwang2,*
1Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Incheon 21936,
2Lab of Cell Differentiation Research, College of Oriental Medicine, Gachon University, Seongnam 13120,
3College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
E-mail: seoul@gachon.ac.kr
Tel: +82-31-750-5421, Fax: +82-31-721-7029
Received: November 5, 2018; Revised: January 24, 2019; Accepted: April 3, 2019; Published online: September 10, 2019.
© The Korean Society of Applied Pharmacology. All rights reserved.

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.
Keywords: Osteoclast, Osteoporosis, Poncirin, RANKL, JNK


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