title: Herbacetin inhibits RANKL-mediated osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.
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.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Sapkota
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea.
authors.forename: Se-woong
authors.initials: SW
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Yunjo
authors.initials: Y
authors.lastname: Soh
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000150:complications; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053245:RANK Ligand; D012333:RNA, Messenger; D014157:Transcription Factors; C581534:herbacetin
keywords: Bone loss; Herbacetin; NFATc1; Osteoclast; RANKL