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Background: Human skeletal muscle stem cells (hSMSCs) can differentiate into bone and fat cells. Results: hSMSCs could also differentiate into odontoblasts but required an extracellular matrix scaffold and changes in their integrin profile. Conclusion:The present results identify an odontoblast differentiation pathway dependent on adhesion receptor expression. Significance: The data provide insight into how hSMSC adhesion receptors interact with the microenvironment to regulate lineage specification.

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We established a differentiation method for homogeneous α7 integrin-positive human skeletal muscle stem cell (α7+hSMSC)-derived osteoblast-like (α7+hSMSC-OB) cells, and found that interleukin (IL)-1β 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-1β was mediated by Wingless/int1 (Wnt) signaling and increased the proliferation of osteoblast-like cells. IL-1β 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-1β-induced increase in cell proliferation. We revealed that a unique signaling cascade IL-1β→Wnt16→Lrp5→MMP-13, was intimately involved in the proliferation of osteoblast-like cells, and suggest that IL-1β-induced MMP-13 expression and changes in cell proliferation are regulated by Wnt16.

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