Figure 1.

(A) Three possibilities are operative in ectopic calcification pathogenesis: healthy cells can directly acquire an osteogenic phenotype; there is a step-wise progression where cells transition through a progenitor-like state before acquiring an osteogenic phenotype; healthy cells de-differentiate into progenitor-like cells and are able to stay in this pluripotent state for some time, followed by a cue inducing them re-differentiate back to their initial state or transdifferentiate into calcifying cells. (B) Coinciding with these three possibilities, it is unknown whether these phenotypic transitions are regulated at the transcriptional level of osteogenic genes or whether there are more global epigenetic changes that alter the cell at a more global level