The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264.7 cells
- Authors
- Kim, Hyun-Sook; Suh, Kwang Sik; Sul, Donggeun; Kim, Byung-Jo; Lee, Seung Kwan; Jung, Woon-Won
- Issue Date
- 2월-2012
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- glabridin; flavonoid; osteoclastogenesis; bone resorption; receptor activator of nuclear factor-kappa B ligand; signaling pathway
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, v.29, no.2, pp.169 - 177
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
- Volume
- 29
- Number
- 2
- Start Page
- 169
- End Page
- 177
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/106127
- DOI
- 10.3892/ijmm.2011.822
- ISSN
- 1107-3756
- 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-kappa B 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 NFATcl, 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.
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Collections - Graduate School > Department of Medicine > 1. Journal Articles
- College of Medicine > Department of Medical Science > 1. Journal Articles
- College of Health Sciences > School of Health and Environmental Science > 1. Journal Articles
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