title: TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol.
abstract: Kaempferol (KMP) exerts protective effects against both osteoporosis and obesity by regulating cellular activities, but the underlying molecular mechanisms have not been fully elucidated. TAZ (transcriptional coactivator with PDZ-binding motif) modulates both osteoblast and adipocyte differentiation from mesenchymal stem cells by stimulating the activities of RUNX2 (runt-related transcription factor 2) and suppressing the activities of PPARγ (peroxisome proliferator-activated receptor γ). In this study, we investigated the effects of KMP on TAZ regulated osteoblast and adipocyte differentiation. KMP increased the osteoblast differentiation of mesenchymal cells by facilitating the physical interaction between TAZ and RUNX2, thus the increasing transcriptional activities of RUNX2. KMP also enhanced the association of TAZ with PPARγ, thereby suppressing the gene transcription of PPARγ targets and resulting in diminished adipocyte differentiation. Interestingly, the regulatory effects of kaempferol on RUNX2 and PPARγ-mediated transcriptional activity were impaired in TAZ-null mouse embryonic fibroblasts but recovered by restoration of TAZ expression. Our results demonstrate that KMP fortifies TAZ activity, which enhances RUNX2-mediated osteoblast differentiation and suppresses PPARγ-stimulated adipocyte differentiation, indicating the potential of KMP as an effective therapeutic reagent for controlling bone loss and adiposity through TAZ activation.
authors: School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
authors: Mi Ran
authors: MR
authors: Byun
authors: Hana
authors: H
authors: Jeong
authors: Su Jung
authors: SJ
authors: Bae
authors: A Rum
authors: AR
authors: Kim
authors: Eun Sook
authors: ES
authors: Hwang
authors: Jeong-Ho
authors: JH
authors: Hong
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D044949:Kaempferols / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D047908:Intracellular Signaling Peptides and Proteins; D044949:Kaempferols; D047495:PPAR gamma; C493709:RUNX2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; C006552:kaempferol