title: Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells.
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-LRP5(T253) and hMSC-LRP5(T244) 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.
authors.affiliation: Laboratory for Molecular Endocrinology (KMEB), Department of Endocrinology and Metabolism, University Hospital of Odense, Odense C, Denmark.
authors.forename: Weimin
authors.initials: W
authors.lastname: Qiu
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000873:Anthracenes / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000873:Anthracenes; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C449091:NKD1 protein, human; D047428:Protein Kinase Inhibitors; C555510:WNT3A protein, human; D051153:Wnt Proteins; C540523:Wnt11 protein, human; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; C432165:pyrazolanthrone; D048670:MAP Kinase Kinase 4