Many EV mRNAs were regulated overtime during the progression of osteoporosis in our mice, including genes encoding proteins involved in osteoclast (Acp5, Adcy10, Calca, Ctsk, Pth, Il-6, Tnfsf11, Vegfa) [41–43] and osteoblast (Dkk1, Enpp1, Il-6, Lrp6, Wnt3a) [44, 45] formation, regulation and activity, as well as in bone matrix assembly and mineralization (Alpl, Bglap, Col1a1) [46] and in coupling bone resorption with bone formation (Tgfb1, Ltbp2) [47]. The gene discussed is ENPP1; the disease is osteoporosis.