Intriguingly, unlike genes in receptors and ligands, we further noticed that twelve out of sixteen antagonist genes showed enhanced expression in MSCs of primary osteoporosis in comparison to their age-matched controls (Fig. 7B, right panel); these include those genes supposed to be down-regulated by SMAD signaling in our study, such as Fstl3, Fstl4, Fstl5, Sostdc1, Sost and Cer1 (Fig. 4). This evidence concerns the gene SOSTDC1 and osteoporosis.