Trichostatin A enhances osteogenic differentiation through activation of ERK pathways in mouse bone marrow multipotent stromal cells

Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, is a potentially important anticancer agent. TSA has been extensively studied for inducing various malignancies concerning growth inhibition, cell cycle arrest, and apoptosis. TSA reportedly modulates the expression of several genes by inhibiting the activity of HDACs, including genes involved in cell differentiation and proliferation. The present study investigated osteoblastic differentiation concerning the mechanism of TSA in D1 multipotent mouse bone marrow stromal cells. D1 cells were cultured in osteogenic differentiation medium (ODM) for 6 days, treated with TSA for 1 day and then analyzed for viability, alkaline phosphatase (ALP) activity, Ca++ bone marrow stromal cells (alizarin red S staining), gene expression (reverse transcriptase-polymerase chain reaction) and protein production (Western blotting). TSA promoted ALP protein production. TSA induced formation of mineralized nodules in bone marrow stromal cells. Western blotting showed that TSA activated phosphorylation of extracellular signal-regulated kinase 1/2 in D1 cells. These findings indicate that TSA triggers osteoblast differentiation by activation of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling pathway and via the expression of ALP activity in osteoblasts. TSA may be a promising target that could be developed for supplementation of osteoporotic diseases.