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Eur J Pharmacol. 2016 Apr 15;777:17-25. doi: 10.1016/j.ejphar.2016.02.057. Epub 2016 Feb 26.

Herbacetin inhibits RANKL-mediated osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.

Author information

1
Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea.
2
Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea. Electronic address: ysoh@jbnu.ac.kr.

Abstract

Herbacetin is an active flavonol (a type of flavonoid) that has various biologic effects such as antioxidant, antitumor, and anti-inflammatory activities. However, one of its novel effects remains to be investigated, that is, the induction of osteoclastogenesis by the receptor activator of nuclear factor-κB ligand (RANKL). In this study, we examined the effects and mechanisms of action of herbacetin on osteoclastogenesis in RANKL-treated bone marrow-derived macrophages (BMMs) and murine macrophage RAW264.7 cells in vitro and on lipopolysaccharide (LPS)-induced bone destruction in vivo. Herbacetin significantly inhibited RANKL-induced osteoclast formation and differentiation in BMMs and RAW264.7 cells in a dose-dependent manner. Moreover, the suppressive effect of herbacetin resulted in a decrease in osteoclast-related genes, including RANK, tartrate-resistant acid phosphatase, cathepsin K, and matrix metalloproteinase-2 and -9 (MMP-9). Consistent with mRNA results, we confirmed that herbacetin treatment downregulated protein expression of MMP-9 and cathepsin K. Herbacetin also decreased induction of the osteoclastogenic transcription factor c-Fos and nuclear factor of activated T cells c1 (NFATc1) and blocked RANKL-mediated activation of Jun N-terminal kinase (JNK) and nuclear factor-κB. Herbacetin clearly inhibited the bone resorption activity of osteoclasts on plates coated with fluorescein-labeled calcium phosphate. More importantly, the application of herbacetin significantly reduced LPS-induced inflammatory bone loss in mice in vivo. Taken together, our results indicate that herbacetin has potential for use as a therapeutic agent in disorders associated with bone loss.

KEYWORDS:

Bone loss; Herbacetin; NFATc1; Osteoclast; RANKL

PMID:
26923730
DOI:
10.1016/j.ejphar.2016.02.057
[Indexed for MEDLINE]

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