1. [Chidamide Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells from Patients with Myelodysplastic Syndromes].
- Author
-
Zhao SD, Guo J, Zhao YS, and Chang CK
- Subjects
- Humans, Cells, Cultured, Bone Marrow Cells, Benzamides pharmacology, Histone Deacetylases metabolism, Alkaline Phosphatase metabolism, Mesenchymal Stem Cells cytology, Osteogenesis drug effects, Myelodysplastic Syndromes, Cell Differentiation drug effects, Aminopyridines pharmacology, Core Binding Factor Alpha 1 Subunit metabolism, Cell Proliferation drug effects
- Abstract
Objective: To explore the effects and mechanisms of chidamide on the osteogenic differentiation of bone marrow mesenchymal stromal cells (MSC) from myelodysplastic syndromes (MDS)., Methods: MSC were isolated and cultured from bone marrow of MDS patients and healthy donors. CCK-8 assay was used to detect the effects of chidamide on the proliferation of MSC. The effects of chidamide on the activity of histone deacetylase (HDAC) in MSC was measured by a fluorescence assay kit and Western blot. Alkaline phosphatase (ALP) activity was detected on day 3 and calcium nodule formation was observed by Alizarin Red staining on day 21 after osteogenic differentiation. The expression of early and late osteogenic genes was detected on day 7 and day 21, respectively. RT-PCR and Western blot were used to detect the effects of chidamide on mRNA and protein expression of RUNX2 which is the key transcription factor during osteogenesis., Results: As the concentration of chidamide increased, the proliferation of MSC was inhibited. However, at a low concentration (1 μmol/L), chidamide had no significant inhibitory effect on MSC proliferation but significantly inhibited HDAC activity. In MSC from both MDS patients and healthy donors, chidamide (1 μmol/L) significantly increased ALP activity, calcium nodule formation, thereby mRNA expression of osteogenic genes, and restored the reduced osteogenic differentiation ability of MDS-MSC compared to normal MSC. Mechanistic studies showed that the osteogenic-promoting effect of chidamide may be related to the upregulation of RUNX2 ., Conclusion: Chidamide can inhibit HDAC activity in MSC, upregulate the expression of the osteogenic transcription factor RUNX2 , and promote the osteogenic differentiation of MDS-MSC.
- Published
- 2024
- Full Text
- View/download PDF