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HDAC Inhibitor LMK-235 Promotes Odontoblast Differentiation

October 21, 2019

Dental pulp, the living tissue in the core of teeth, contains stem cells. Dental pulp stem cells are of medical interest because they can differentiate into odontoblasts, osteoblasts, adipocytes, and chondrocytes, and because they can be obtained using minimally invasive methods.

The mechanism of dental pulp stem cell differentiation is not currently understood. Liu et al. suspect that epigenetic modifications controlled by histone deacetylaces (HDACs) play a role. Previous studies have shown that HDAC inhibition promotes stem cell differentiation into odontoblasts.

The molecule LMK-235 is an inhibitor of HDAC4 and HDAC5. Recently, Liu et al. investigated whether LMK-235 can promote dental pulp cell differentiation into odontoblasts. They cultured dental pulp cells from waste wisdom teeth and applied a series of doses of LMK to the culture fluid.

At high doses, LMK-235 inhibits cell proliferation. Liu et al. used a low dose, 100nM, for the rest of the experiment. At 100nM, LMK-235 increased the mRNA expression of genes associated with differentiation such as DSPP, ALP, and Runx2. A Western blot showed that LMK-235 increased the protein expression of DSPP and Runx2. The treated cells also showed more calcified nodules in culture.

Liu et al. acknowledge that their evidence in this study is indirect, because the cultured cells did not fully differentiate into odontoblasts. However, the results show that dental pulp cells hold promise for the field of regenerative medicine.

L493400 LMK-235

 

 

Liu Z, Chen T, Han Q, Chen M, You J, Fang F, Peng L, Wu B. HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells. 2018. Molecular medicine reports. 17:1445-1452.

Tags: HDAC inhibitor, LMK-235, odontoblast Categories: News

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