RRC ID 53876
Author Kida J, Hata K, Nakamura E, Yagi H, Takahata Y, Murakami T, Maeda Y, Nishimura R.
Title Interaction of LEF1 with TAZ is necessary for the osteoblastogenic activity of Wnt3a.
Journal Sci Rep
Abstract Canonical Wnt signalling plays an important role in osteoblast differentiation and bone formation. However, the molecular mechanisms by which canonical Wnt signalling exerts its osteoblastogenic effect remain elusive. Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Reporter assay and co-immunoprecipitation experiments revealed functional and physical interaction between LEF1 and TAZ. Overexpression of dominant-negative forms of either LEF1 or TAZ markedly inhibited Wnt3a-dependent osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. Additionally, Wnt3a enhanced osteoblast differentiation induced by bone morphogenetic protein 2 (BMP2), which stimulates osteoblast differentiation by regulating Runx2. Collectively, these findings suggest that interaction between LEF1 and TAZ is crucial for the osteoblastogenic activity of Wnt3a and that LEF1 and TAZ contribute to the cooperative effect of Wnt3a and BMP2 on osteoblast differentiation through association with Runx2.
Volume 8(1)
Pages 10375
Published 2018-7-10
DOI 10.1038/s41598-018-28711-4
PII 10.1038/s41598-018-28711-4
PMID 29991769
PMC PMC6039525
MeSH Bone Morphogenetic Protein 2 / metabolism Cell Differentiation Cell Line Core Binding Factor Alpha 1 Subunit / metabolism Humans Intracellular Signaling Peptides and Proteins / metabolism* Lymphoid Enhancer-Binding Factor 1 / metabolism* Osteoblasts / cytology* Protein Binding Trans-Activators Transcription Factors Transcriptional Coactivator with PDZ-Binding Motif Proteins Transfection Wnt Signaling Pathway Wnt3A Protein / physiology*
IF 3.998
Times Cited 2
DNA material pAxCAwt (RDB01678)
Human and Animal Cells ST2(RCB0224)