ISG15 and Osteopenia: It was postulated that Isg15 might be one of the relevant downstream targets of Fzd9 in the regulation of bone formation, because the impaired activity of the Fzd9-deficient osteoblast to form mineralized matrix could be rescued after transduction of an Isg15 retrovirus and because Isg15-deficient mice displayed osteopenia [28].