title: 3'4'7-Trihydroxyflavone inhibits RANKL-induced osteoclast formation via NFATc1.
abstract: 3'4'7-Trihydroxyflavone is a flavonoid from ladino clover, alfalfa, and Albizzia julibrissin. In the present study, we found that 3'4'7-trihydroxyflavone markedly inhibited the receptor activator of nuclear factor kappa B ligand (RANKL) induced osteoclastic differentiation from mouse bone marrow derived macrophages (BMMs). 3'4'7-trihydroxyflavone also reduced the mRNA expression level of osteoclastic marker genes including calcitonin receptor (CTR), Cathepsin K1 v-ATPase V0 subunit d2 (ATP6v0d2), and dendritic cell-specific transmembrane protein (DC-STAMP). In addition, 3'4'7-trihydroxyflavone decreased the bone resorption activity of osteoclasts on dentin slices. We found that 3'4'7-trihydroxyflavone inhibited RANKL-induced expression of nuclear factor of activated T cells c1 (NFATc1), a key transcription factor of osteoclast differentiation. Furthermore, 3'4'7-trihydroxyflavone attenuated RANKL-induced activation of p38 mitogen-activated protein kinase (MAPK) and expression of B lymphocyte-induced maturation protein 1 (Blimp1), a repressor of negative regulators of NFATc1. Taken together, our data suggest that 3'4'7-trihydroxyflavone inhibits osteoclastogenesis via NFATc1.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.forename: Juhyun
authors.initials: J
authors.lastname: Lee
authors.forename: Miran
authors.initials: M
authors.lastname: Moon
authors.forename: Mijung
authors.initials: M
authors.lastname: Yim
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control; D005419:Flavonoids / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C587591:3',4',7-trihydroxyflavone; D005419:Flavonoids; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C513258:Prdm1 protein, mouse; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D048051:p38 Mitogen-Activated Protein Kinases