Journal de recherche et de thérapie sur les cellules souches

Abstrait

Histone Deacetylase Inhibitors can Repress Proliferation and Induce Apoptosis in Gingiva Progenitor Cells from Idiopathic Gingival Fibromatosis

Zhi Jia, Chunyue Feng, Yingchenyao Wang, Jingkun Li, Tingting Zhang, Jian Zhang and Dayong Liu

Objective: Idiopathic gingival fibromatosis (IGF), which is characterized by diffuse enlargement of the gingiva due to expansion and accumulation of connective tissue, is a relatively rare hereditary condition that has no specific cause. The aim of this study was to investigate whether the anti-tumor drugs trichostatin A (TSA; inhibits histone deacetylase) and panobinostat (LBH589; a non-selective inhibitor of histone deacetylase) inhibit the proliferation of cells derived from gingiva in patients with IGF.
Materials and methods: After osteogenic differentiation and adipogenic induction, the differences between normal gingival mesenchymal stem cells ( N-GMSCs ) and hyperplastic gingival mesenchymal stem ( H-GMSCs, theI cells from IGF ) were determined in terms of alkaline phosphatase staining and activity, alizarin red staining, calcium-nodule formation and, lipid droplets,. The effects of TSA and LBH589 were investigated via the MTT assay, flow cytometry, and reverse transcription polymerase chain reaction (RT-PCR).
Results: Alkaline phosphatase staining and activity, alizarin red staining, lipid droplets detected the differentiative capacity in normal and IGF cells. These assays indicated that IGF cells possess multipotent differentiation properties similar to those of normal cells. RT-PCR showed that mRNA levels of the gene encoding p21Waf/Cip1, a cyclin-dependent kinase inhibitor and an essential regulator of growth inhibition, were lower in H-GMSCs than in N-GMSCs. After exposure to 1000 nM TSA or 1000 nM LBH589 for 48 h, p21Waf/Cip1 mRNA levels increased in H-GMSCs.
Conclusions: TSA and LBH589 can repress the growth and proliferation of hyperplastic IGF cells by regulating p21Waf/Cip1 mRNA levels.