Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells |
| |
| Authors: | Qiu Weimin Chen Li Kassem Moustapha |
| |
| Institution: | aLaboratory for Molecular Endocrinology (KMEB), Department of Endocrinology and Metabolism, University Hospital of Odense, Odense C, Denmark;bStem Cell Unit, Department of Anatomy, King Saud University, Riyadh, Saudi Arabia |
| |
| Abstract: | The canonical Wnt signaling pathway can determine human bone marrow stromal (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte lineages. However, its downstream targets in MSC are not well characterized. Thus, using DNA microarrays, we compared global gene expression patterns induced by Wnt3a treatment in two hMSC lines: hMSC-LRP5T253 and hMSC-LRP5T244 cells carrying known mutations of Wnt co-receptor LRP5 (T253I or T244M) that either enhances or represses canonical Wnt signaling, respectively. Wnt3a treatment of hMSC activated not only canonical Wnt signaling, but also the non-canonical Wnt/JNK pathway through upregulation of several non-canonical Wnt components e.g. naked cuticle 1 homolog (NKD1) and WNT11. Activation of the non-canonical Wnt/JNK pathway by anisomycin enhanced osteoblast differentiation whereas its inhibition by SP600125 enhanced adipocyte differentiation of hMSC. In conclusion, canonical and non-canonical Wnt signaling cooperate in determining MSC differentiation fate. |
| |
| Keywords: | Mesenchymal stem cell Wnt/JNK Wnt/β-catenin Osteogenesis Adipogenesis |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
