Wnt signaling was confirmed to be reduced by demonstrating reduced nuclear β-catenin in Enpp1asj osteoblasts by knocking out Sfrp1, which restored both mineralization in the differentiating cell cultures and the nuclear β-catenin signaling, supporting the notion that Sfrp1-mediated inhibition of Wnt is responsible for the osteopenia observed in ENPP1 deficiency (Figure 6h). This evidence concerns the gene SFRP1 and Osteopenia.