| 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
|
| Resource |
| DNA material |
pAxCAwt (RDB01678) |
| Human and Animal Cells |
ST2(RCB0224)
10T1/2(RCB0247) |
