Abstract
Wnt5a plays an essential role in tissue development by regulating cell migration, though the molecular mechanisms are still not fully understood. Our study investigated the pathways involved in Wnt5a-dependent cell motility during the formation of dentin and pulp. Over-expression of Wnt5a promoted cell adhesion and formation of focal adhesion complexes (FACs) in human dental papilla cells (hDPCs), while inhibiting cell migration. Instead of activating the canonical Wnt signal pathway in hDPCs, Wnt5a stimulation induced activation of the JNK signal in a RhoA-dependent or independent manner. Inhibiting JNK abrogated Wnt5a-induced FACs formation but not cytoskeletal rearrangement. Both dominant negative RhoA (RhoA T19N) and constitutively active RhoA mutants (RhoA Q63L) blocked the Wnt5a-dependent changes in hDPCs adhesion, migration and cytoskeletal rearrangement here too, with the exception of the formation of FACs. Taken together, our study suggested that RhoA and JNK signaling have roles in mediating Wnt5a-dependent adhesion and migration in hDPCs, and the Wnt5a/JNK pathway acts both dependently and independently of the RhoA pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Adhesion / genetics
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Cell Movement* / genetics
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Cytoskeleton / metabolism
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Dental Papilla / cytology*
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Dental Papilla / metabolism*
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Enzyme Activation
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Gene Expression Regulation
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Myosin Light Chains / metabolism
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Paxillin / metabolism
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Phosphorylation
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Protein Transport
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction*
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Wnt Proteins / genetics
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Wnt Proteins / metabolism*
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Wnt-5a Protein
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beta Catenin / genetics
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beta Catenin / metabolism
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rhoA GTP-Binding Protein / metabolism*
Substances
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Myosin Light Chains
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Paxillin
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Proto-Oncogene Proteins
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WNT5A protein, human
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Wnt Proteins
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Wnt-5a Protein
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beta Catenin
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JNK Mitogen-Activated Protein Kinases
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rhoA GTP-Binding Protein
Grants and funding
This work was supported by NSFC Grant 81070801 and 81200759, New Century Excellent Talents Fund NCET-10-0577, Innovative Research Team of Education Department of Sichuan Province 13TD0038, Sichuan Province Science and Technology Support Program 2012SZ0034 and Scientific Research Foundation of Sichuan University Young Teachers 2012SCU11900-4. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.