SMAD1 and Osteopenia: BM cells from the femurs and tibias of recipient mice injected with SM-EVs (from patients with tryptase >110 ng/ml) or SM-EVs from patients with osteopenia/osteoporosis showed markedly reduced mRNA expression levels of Alp, Runx2, Smad1/5, and to a lesser extent Smad2 (Fig. 8d).