Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis

Table 1

DNA methylation in MSC aging and related diseases.

Regulatory factors	Mechanism	In vivo or in vitro	Consequence	Materials	Ref.
Senescence and aging
DNMT1↓; DNMT3b↓	Decreases methylation in the promoter region of miRNA targeting Ezh2 to decrease Ezh2 expression, thus inhibiting repressive H3K27me3 formation at p16’s promoter; directly decreases methylation in CDK inhibitor genes p16 and p21	In vitro	Aging	hUCSCs	[28]
DNMT↓	Insufficient to methylate Tert promoter; thus upregulated TERT would repair the shortened telomeres with replication	In vitro	Antisenescence	hBMSCs	[30]
Skeletal diseases
DNMT1 changes	Aberrant methylation of ABCB1 gene leads to a dysregulation of glucocorticoid	In vitro	ONFH	hBMSCs	[33]
TET1 and TET2↓	The depletion of TET causes impeded demethylation of P2rX7 promoter and incapable exosome release, which leads to intracellular accumulated miR-297 targeting Runx2 signaling pathway	Both	Osteoporosis	hBMSCs, mouse BMSCs, mouse model	[34]