Low-dose tubacin promotes BMSCs proliferation and morphological changes through the ERK pathway.

Abstract

Histone deacetylase 6 (HDAC6) plays critical roles in many cellular processes related to cancer, but its epigenetic regulation in bone marrow stromal stem cells (BMSCs) remains unexplored. This study investigated the beneficial effects of Tubulin Acetylation Inducer (tubacin), a novel specific HDAC6 inhibitor, on the proliferation and migration of BMSCs. A low concentration of tubacin promoted BMSC commitment and enhanced proliferation of BMSCs. Atomic force microscopy results showed that tubacin induced morphological changes and enhanced the mechanical properties of BMSCs. Furthermore, low tubacin concentrations significantly upregulated protein expression of acetylated α-tubulin, VCAM-1, and ICAM-1, which could be suppressed by an ERK inhibitor. Protein chip analysis showed that there were significant changes in the expression levels of 49 cytokines after tubacin treatment, which participate in inflammatory responses and cell activation, proliferation, and differentiation. Our findings suggest that the protective effects of tubacin on BMSCs involve HDAC6 inhibition by activating the ERK pathway.