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 PPAR gamma (peroxisome proliferator-activated receptor gamma). 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 PPAR gamma, thereby suppressing the gene transcription of PPAR gamma targets and resulting in diminished adipocyte differentiation. Interestingly, the regulatory effects of kaempferol on RUNX2 and PPAR gamma-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 PPAR gamma-stimulated adipocyte differentiation, indicating the potential of KMP as an effective therapeutic reagent for controlling bone loss and adiposity through TAZ activation. (C) 2011 Elsevier Inc. All rights reserved.