Biomolecules & Therapeutics

  • 제28권4호
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  • Pages.337-343
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  • 2020
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Poncirin Inhibits Osteoclast Differentiation and Bone Loss through Down-Regulation of NFATc1 In Vitro and In Vivo

  • Chun, Kwang-Hoon (Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University) ;
  • Jin, Hyun Chul (Lab of Cell Differentiation Research, College of Oriental Medicine, Gachon University) ;
  • Kang, Ki Sung (Lab of Cell Differentiation Research, College of Oriental Medicine, Gachon University) ;
  • Chang, Tong-Shin (College of Pharmacy, Seoul National University) ;
  • Hwang, Gwi Seo (Lab of Cell Differentiation Research, College of Oriental Medicine, Gachon University)
  • 투고 : 2018.11.05
  • 심사 : 2019.04.03
  • 발행 : 2020.07.01
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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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References

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