Table 2.

Epigenetics-based strategy for MSC aging and age-related diseases.

Histone modification	Drugs or regulator	Histone modifier	Mechanism	Therapeutic effect	Reference
Up-regulation of the decreased levels of histone methylation	Twist-1	EZH2	Increase H3K27me3 along the Ink4A/Arf locus, repress transcription of both P16/P14	Reduce the ratio of senescent cells and continued to proliferate	43
	1,25(OH)2D3	EZH2	Up-regulate Ezh2 via the vitamin D receptor (VDR)-mediated transcription to increase H3K27me3.	Prevent bone loss	74
	1,25(OH)2D3	unknown	Up-regulate H3K9me2 and down-regulate H3ac at the BMP2 promoter region and activated the Wnt/β-catenin signaling.	Prevent bone loss	75
	Lentivirus transduction	ASH1L	Regulate the enrichment of H3K4me3 at the Hoxa10, Osx, Runx2, and Sox9 promoters	Facilitate osteogenesis and chondrogenesis, suppress adipogenesis	54
	LBP	SETD2	This leads to a decrease of H3K36me3 in the Lbp gene body	Rescue the lack of osteogenesis and enhanced adipogenesis	56
	siRNA Transfection	CARM1	Bind to the promoter region of DDR2 and methylated H3R17	Senescence cells were decreased	58
	BMP2	KDM5A	Increase the H3K4me3 level at the Runx2 promoter	Rescue bone loss and the decrease in bone formation	51
	Pargyline	LSD1	Enhance the dimethylation level of H3K4 at the promoter regions of Runx2 and Bglap genes	Rescue or prevent the osteoporotic	77
Down-regulation of the increased levels of histone methylation	Retroviral transduction	KDM6A	Remove H3K27me3 at the Runx2 and osteocalcin TSS.	Promote bone formation	46
	BMP-4/7	KDM4B KDM6B	Promote DLX expression by demethylating H3K9me3. Control HOX gene expression by demethylating H3K27me3.	Promote bone regeneration and repair	41
	DZNep	EZH2	Reduce EZH2 expression, decreased H3K27me3 levels on promoters of Wnt1, Wnt6, and Wnt10a	Increase trabecular bone, enhance osteogenic differentiation, and inhibit adipogenesis	42
	DZNep	EZH2	Reduce EZH2 expression, decrease H3K27me3 at the Runx2 and Bglap TSS	Increase mineral deposit	46
	Chaetocin	SUV39 family	Suppress H3K9 methylation via Wnt/β-catenin signaling pathways	Increase in bone tissue	78
Up-regulation of the decreased levels of histone acetylation	Lentivirus transduction	GCN5	Increasing H3K9ac on the promoters of Wnt genes	Attenuate bone loss during osteoporosis	65
	Retroviral infection	PCAF	Control BMP signaling gene expression by increasing H3K9ac.	Inhibit adipocyte	67
	AA	PcG KMD6B	Repress KDM6B expression and sustain PcG expression	Downregulate P16INK4A expression levels	60
	VPA	HDAC8	Promote the level of H3K9ac and enhance the expression of osteogenesis-related genes	Accelerate the osteogenic mineralization	79
	HDAC9 inhibitors	HDAC9	Maintains the levels of acetylation modifications on H3K9 of autophagy-related genes	Promote osteogenic differentiation and repress adipogenic	62
	bFGF	unknown	Regulate H3K9ac and H3K14ac at TERT, OCT4, SOX2, RUNX2, and ALP promoter regions	Promote MSC proliferation	68
Down-regulation of the increased levels of histone acetylation	Lentiviral transduction	SIRT6	Deacetylate H3K56 at the HO-1 promoter.	Delayed cellular senescence	70
	GSK343	HDAC9c	Regulate the EZH2-HDAC9c regulatory axis, sequester PPARγ-2 and allow RUNX2 to turn on OPN transcription.	Enhance osteogenesis and suppress adipogenesis	72