The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264.7 cells

Hyun Sook Kim, Kwang Sik Suh, Dong Geun Sul, Byung Jo Kim, Seung Kwan Lee, Woon Won Jung

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Osteoblastic bone formation and osteoclastic bone resorption are in balance to maintain a constant, homeostatically controlled amount of bone. Excessive bone resorption by osteoclasts is involved in the pathogenesis of bone-related disorders. In the present study, we evaluated the inhibitory effects of glabridin, a flavonoid purified from licorice root, on the receptor activator of nuclear factor-κB ligand (RANKL)- induced osteoclast differentiation and its molecular mechanisms in murine osteoclast progenitor RAW264.7 cells. Glabridin significantly inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity, the formation of multinucleated osteoclasts and resorption-pit formation. In mechanistic studies of the anti-osteoclastogenic potential of glabridin, we found that glabridin inhibited RANKL-induced expression of c-Fos and subsequent expression of NFATc1, which is a master regulator of osteoclastogenesis. Interestingly, glabridin inhibited the RANKL-induced expression of signaling molecules (TRAF6, GAB2, ERK2, JNK1 and MKK7) and osteoclast survival-related signaling pathways such as c-Src, PI3K and Akt2. Glabridin also inhibited the bone resorptive activity of mature osteoclasts by inhibiting osteoclast-associated genes (cathepsin K, MMP-9, CAII, TCIRG1, OSTM1 and CLCN7). Taken together, our data suggest that glabridin holds great promise for use in preventing osteoclastogenesis by inhibiting RANKL-induced activation of signaling molecules and subsequent transcription factors in osteoclast precursors and these findings may be useful for evaluating treatment options in bone-destructive diseases.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalInternational Journal of Molecular Medicine
Volume29
Issue number2
DOIs
Publication statusPublished - 2012 Feb 1

Fingerprint

Osteoclasts
Osteogenesis
Bone Resorption
Bone and Bones
TNF Receptor-Associated Factor 6
Cathepsin K
Glycyrrhiza
glabridin
Bone Diseases
Cytoplasmic and Nuclear Receptors
Matrix Metalloproteinases
Phosphatidylinositol 3-Kinases
Flavonoids
Transcription Factors
Stem Cells
Ligands
Genes

Keywords

  • Bone resorption
  • Flavonoid
  • Glabridin
  • Osteoclastogenesis
  • Receptor activator of nuclear factor-κB ligand
  • Signaling pathway

ASJC Scopus subject areas

  • Genetics

Cite this

The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264.7 cells. / Kim, Hyun Sook; Suh, Kwang Sik; Sul, Dong Geun; Kim, Byung Jo; Lee, Seung Kwan; Jung, Woon Won.

In: International Journal of Molecular Medicine, Vol. 29, No. 2, 01.02.2012, p. 169-177.

Research output: Contribution to journalArticle

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