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Publication : IL-1β-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway.

First Author  Ozeki N Year  2014
Journal  Exp Cell Res Volume  328
Issue  1 Pages  69-86
PubMed ID  24851717 Mgi Jnum  J:217133
Mgi Id  MGI:5613097 Doi  10.1016/j.yexcr.2014.05.006
Citation  Ozeki N, et al. (2014) IL-1beta-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway. Exp Cell Res 328(1):69-86
abstractText  We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into alpha2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1beta induces matrix metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis in these cells, suggesting that MMP-3 plays a potentially unique physiological role in the regeneration of odontoblast-like cells. Here, we examined whether up-regulation of MMP-3 activity by IL-1beta was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1beta increased mRNA and protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and Wnt5b were found to increase MMP-3 mRNA, protein and activity, and interestingly the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a, Wnt5b and Lrp5 suppressed the IL-1beta-induced increase in MMP-3 expression and suppressed cell proliferation, an effect rescued by application of exogenous Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP-3 in effecting IL-1beta-induced proliferation of ES cell-derived odontoblast-like cells.
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