Among the many cytokines, TNF-α has been demonstrated as a particularly important regulator in CAVD that triggers the transition of valvular smooth muscle cells and myofibroblasts to myofibroblasts via activating Wnt pathway activation and increasing ALP, BMP-2, and RUNX2 expression [35–37]. This evidence concerns the gene RUNX2 and congenital bilateral aplasia of vas deferens from CFTR mutation.