Anti-WNT5B monoclonal antibody Made to order

We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into alpha 2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1 beta 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-1 beta was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1 beta 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-1 beta-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-1 beta-induced proliferation of ES cell-derived odontoblast-like cells. (C) 2014 Elsevier Inc. All rights reserved.