Second, the pleiotropic nature of miRNAs creates a risk of unpredictable downstream consequences, particularly given the “bone-vascular axis.” For instance, while Zeng et al. demonstrated that inhibiting the TRPM3/miR-204 axis with Puerarin promotes osteoblast differentiation and reverses bone loss (91), systemic inhibition of miR-204 could theoretically exacerbate aortic valve calcification, where miR-204 functions as a critical repressor of Runx2. This evidence concerns the gene RUNX2 and aortic valve calcification.