Besides, depletion of demethylase TET1 and TET2 causes osteopenia phenotype in mice by impeding demethylation of P2rX7 promoter; P2rX7 deficiency further leads to MSC incapability of exosome release, which results in intracellular accumulated miR-297 targeting Runx2 signaling pathway [34]. Here, P2RX7 is linked to Osteopenia.