Table 2.
Histone acetyltransferases, histone deacetylases, and their roles in the occurrence and development of osteoporosis.
| HATs and HDACs | Target genes | Function |
|---|---|---|
| KAT2A (GCN5) | Wnt, NF-κB | Enhances osteogenic differentiation ability of BMSCs (49–51). |
| KAT2B (PCAF) | BMP, Runx2 (52), CXCL12 (53) NFATc1 (54) | Promotes osteogenic differentiation of MSCs (52, 53). Promotes osteoclast differentiation (54) |
| CBP/p300 | Runx2 (55), NFATc1 (54) | Promotes osteoblast differentiation (55). Promotes osteoclast differentiation (54). |
| HDAC1 | IGF-1 | Prevents achievement of peak bone mass by inhibiting IGF-1 expression in the liver and IGF-1 signaling in bone (56). |
| HDAC2 | SP7 (57), AKT, FoxO1 (58) | Inhibits osteogenic differentiation of MSCs (57). Activates Akt and thereby suppresses FoxO1 transcription, resulting in enhanced osteoclastogenesis (58). |
| HDAC3 | NF-κB | Controls bone remodeling by suppressing the responsiveness of osteoclast lineage cell to RANKL (59). |
| HDAC4 | MEF2C, MMP13 (60), Runx2 (61) | HDAC4 interacts with MEF2C at the MMP13 promoter and inhibits MMP13 gene transcription (60). Deacetylates and degrades Runx2, leading to reduced osteoblast function (61). |
| HDAC5 | MEF2C (62), NFATc1 (54) | HDAC5 binds and inhibits the function of MEF2C and decreases SOST expression in osteocytes (62). Reduces RANKL- or PCAF-mediated NFATc1 acetylation, stability, and transactivation activity and suppresses osteoclast differentiation (54) |
| HDAC6 | Runx2 | Inactivates Runx2 promoter to block osteogenesis of BMSCs (48). |
| HDAC7 | Mitf | Represses Mitf function and inhibits osteoclast differentiation (63). Represses Runx2 expression and suppresses osteoblast maturation (64). |
| HDAC8 | Runx2 | Suppresses osteogenic differentiation of BMSCs by inhibiting H3K9ac and Runx2 activity (65). |
| HDAC11 | 11β-HSD2 | Suppresses osteogenic differentiation of BMSCs by downregulating H3K9ac and 11β-HSD2 expression (66). |
HAT, histone acetyltransferases; HDAC, histone deacetylase.
KAT2A(GCN5), Lysine acetyltransferase 2A; NF-κB, Nuclear factor kappa B; KAT2B(PCAF), Lysine acetyltransferase 2B; CXCL12, C-X-C motif chemokine ligand 12; CBP, CREB binding protein, IGF-1, Insulin like growth factor 1; SP7, Sp7 transcription factor; Akt, AKT serine/threonine kinase; RANKL, NF-κB ligand-receptor activator; MEF2C, Myocyte enhancer factor 2C; SOST, Sclerostin; Mitf, Melanocyte inducing transcription factor; 11β-HSD2, Hydroxysteroid 11-beta dehydrogenase 2.