title: Baicalein inhibits osteoclast differentiation and induces mature osteoclast apoptosis.
abstract: In bone remodeling, an imbalance caused by increased bone resorption over bone formation leads to adult skeletal diseases such as osteoporosis. Therefore, the development of anti-resorptive agents has still gained more interest. In this study, using cell-based assay systems in RAW264.7 murine macrophage cells, we found that baicalein significantly inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. Interestingly, baicalein inhibited RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF-kappaB) and mRNA expression of osteoclast-associated genes (TRAP, matrix metalloproteinase 9 and c-Src) and another transcription factors (c-Fos, Fra-2 and NFATc1). In addition, baicalein inhibited the bone resorptive activity of mature osteoclasts by inducing apoptosis. The inhibitory effects of baicalein on the formation of mouse bone marrow macrophage-derived osteoclasts and their bone resorptive activity were also observed. In conclusion, although further studies are needed to determine its biological efficacy and precise mechanism in bone, the present results demonstrated that baicalein has a potential to inhibit osteoclast differentiation and induce mature osteoclast apoptosis.
authors.affiliation: Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Shi Yong
authors.initials: SY
authors.lastname: Ryu
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.forename: Joon-Sig
authors.initials: JS
authors.lastname: Choi
authors.forename: Yong Ki
authors.initials: YK
authors.lastname: Min
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001862:Bone Resorption / Q000378:metabolism / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D008264:Macrophages; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D053245:RANK Ligand / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D044950:Flavanones; D016328:NF-kappa B; D053245:RANK Ligand; D014157:Transcription Factors; C006680:baicalein; D020928:Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase