title: 6,4'-Dihydroxy-7-methoxyflavanone inhibits osteoclast differentiation and function.
abstract: 6,4'-Dihydroxy-7-methoxyflavanone (DMF) is a flavonoid isolated from Heartwood Dalbergia odorifera. It has been known that DMF has antioxidant, anti-inflammatory and neuroprotective effects. DMF, however, the efficacy of bone related diseases has not been reported. In this study, we determined DMF's efficacy on osteoclasts differentiation and function using in vitro bone marrow macrophage osteoclast differentiation culture system. DMF inhibited receptor activators of nuclear factor kappa-B ligand (RANKL) induced osteoclastogenesis dose dependently. In addition, DMF decreased osteoclast function through disruption of actin ring formation and consequently suppression of the pit-forming activity of mature osteoclasts. Mechanistically, DMF inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) and c-Fos via inhibition of mitogen activated protein kinases (MAPKs) pathway. Collectively, the inhibition of osteoclasts differentiation and function by DMF suggests that DMF can be a potential therapeutic molecule for osteoclastogenic bone diseases such osteoporosis, rheumatoid arthritis and periodontal diseases.
authors: Institute for New Drug Development, Keimyung University, Dae-gu 704–701, Republic of Korea.
authors: Nam-Kyung
authors: NK
authors: Im
authors: Je-Yong
authors: JY
authors: Choi
authors: Hyuncheol
authors: H
authors: Oh
authors: Youn-Chul
authors: YC
authors: Kim
authors: Gil-Saeng
authors: GS
authors: Jeong
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D044950:Flavanones / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D053245:RANK Ligand / Q000494:pharmacology
chemical_list: C571779:6,4'-dihydroxy-7-methoxyflavanone; D000199:Actins; D050071:Bone Density Conservation Agents; D044950:Flavanones; D053245:RANK Ligand; D020928:Mitogen-Activated Protein Kinases