Retraction: Inflammatory Cytokine-induced MMP-3 Regulates Proliferation of Odontoblast-like Cells Derived from Induced Pluripotent Stem Cells

 Purpose: We previously reported that matrix metalloproteinase (MMP) -3 accelerates wound healing following dental pulp injury in rats. Additionally, we identified that a proinflammatory cytokine mixture (CM; interleukin-1β, tumor necrosis factor-α, and interferon-γ) induced MMP-3 activity in odontoblast-like cells derived from mouse embryonic stem cells, suggesting that MMP-3 plays a potentially unique role in wound healing and dental pulp regeneration in odontoblast-like cells. Here, we investigate whether upregulation of MMP-3 activity by CM regulates the proliferation and apoptosis of purified odontoblast-like cells derived from induced pluripotent stem (iPS) cells.<br> Methods: The proportion of α2 integrin-positive cells in the total differentiated odontoblast-like cell population is a measure of the purity of the iPS cell-derived odontoblast-like cells, and was estimated by FACS analysis to be 98%. Reverse transcriptase polymerase chain reaction, western blotting, an MMP-3 activity assay, a BrdU cell proliferation enzyme-linked immunosorbent assay, and DNA fragmentation analysis were used to evaluate siRNA-mediated down-regulation of MMP-3 expression and activity, and any changes in the proliferative and apoptotic responses associated with this reduced expression.<br> Results: Low concentrations of CM (1 or 3U) induced MMP-3 mRNA and protein expression, increasing MMP-3 activity and cell proliferation (p<.05), but not apoptosis. MMP-3 silencing produced a potent and significant suppression of cytokine-induced MMP-3 expression and activity, decreased cell proliferation and increased apoptosis (p<.05). These effects were restored by application of exogenous MMP-3 (p<.05).<br> Conclusion: Current evidence suggests that low concentrations of CM induce an MMP-3-mediated increase in odontoblast-like cell proliferation, whereas higher concentrations (5U) inhibit cell proliferation and promote apoptosis. Our current data suggests that CM induces MMP-3-regulated cell proliferation and anti-apoptosis effects in odontoblast-like cells derived from iPS cells, in addition to well-documented destructive roles in inflammation.