IJMS, Vol. 17, Pages 221: Wnt16 Signaling Is Required for IL-1?-Induced Matrix Metalloproteinase-13-Regulated Proliferation of Human Stem Cell-Derived Osteoblastic Cells (International Journal of Molecular Sciences)

We established a differentiation method for homogeneous ?7 integrin-positive human skeletal muscle stem cell (?7+hSMSC)-derived osteoblast-like (?7+hSMSC-OB) cells, and found that interleukin (IL)-1? induces matrix metalloproteinase (MMP)-13-regulated proliferation of these cells. These data suggest that MMP-13 plays a potentially unique physiological role in the regeneration of osteoblast-like cells. Here, we examined whether up-regulation of MMP-13 activity by IL-1? was mediated by Wingless/int1 (Wnt) signaling and increased the proliferation of osteoblast-like cells. IL-1? increased the mRNA and protein levels of Wnt16 and the Wnt receptor Lrp5/Fzd2. Exogenous Wnt16 was found to increase MMP-13 mRNA, protein and activity, and interestingly, the proliferation rate of these cells. Treatment with small interfering RNAs against Wnt16 and Lrp5 suppressed the IL-1?-induced increase in cell proliferation. We revealed that a unique signaling cascade IL-1?->Wnt16->Lrp5->MMP-13, was intimately involved in the proliferation of osteoblast-like cells, and suggest that IL-1?-induced MMP-13 expression and changes in cell proliferation are regulated by Wnt16.