Melatonin Enhances Osteoblastogenesis from Senescent Mesenchymal Stem Cells via NSD2 Mediated Chromatin Remodeling [RNA-seq]

Functional crosstalk between histone modifications and chromatin remodeling has emerged as a key regulatory mode of transcriptional control during cell fate decisions, but the underlying mechanisms are not fully understood. Here we demonstrate that RUNX2 and BGLAP osteogenic genes coordinate histone H3 lysine 36 dimethylation (H3K36me2) and transcriptional elongation factor Pol II to regulate chromatin dynamic and gene transcription during osteogenesis. Mechanistically, melatonin favored osteogenic differentiation via the NSD2-mediated modification of H3K36me2 on the promoters of osteogenic driver genes in MSCs from the old donors. Overall design: Examination MSCs from the old donors treated with melatonin and MSCs from different age groups