Poncirin Inhibits Osteoclast Differentiation and Bone Loss Through Down-Regulation of NFATc1 In Vitro and In VivoPoncirin Inhibits Osteoclast Differentiation and Bone Loss Through Down-Regulation of NFATc1 In Vitro and In Vivo
- Other Titles
- Poncirin Inhibits Osteoclast Differentiation and Bone Loss Through Down-Regulation of NFATc1 In Vitro and In Vivo
- Authors
- Chun Kwang-Hoon; Jin Hyun Chul; Kang Ki Sung; Chang Tong-Shin; Hwang Gwi Seo
- Issue Date
- Jul-2020
- Publisher
- 한국응용약물학회
- Keywords
- Osteoclast; Osteoporosis; Poncirin; RANKL; JNK
- Citation
- Biomolecules & Therapeutics, v.28, no.4, pp.337 - 343
- Journal Title
- Biomolecules & Therapeutics
- Volume
- 28
- Number
- 4
- Start Page
- 337
- End Page
- 343
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/78194
- DOI
- 10.4062/biomolther.2018.216
- ISSN
- 1976-9148
- 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.
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