SMAD3 and osteoporosis: By way of contrast, the cluster enriched in healthy controls contained more genes required for conducting SMAD1/5/8 signaling, such as ACVR2A, ACVR1, BMPR1A and SMAD1. Although we did not observe strong correlation between the specific ligand population and osteoporosis in the ligand profiles (Fig. 7B, middle panel), the above differential expression trends suggest that the seesaw balance of SMAD pathways would lean to over-activation of TGF-β-mediated SMAD3 signaling in MSCs of osteoporosis.