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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.