Effects of trichostatin A and phenamil methanesulfonate treatment on gene expression during osteogenic differentiation of senescent rMSCs

Cell fate transitions are governed by coordinated programs involving epigenetic regulators and lineage-specific transcription factors. RNA sequencing was performed to profile transcriptomic responses of senescent rat mesenchymal stem cells (rMSCs) subjected to a sequential small-molecule treatment paradigm designed to enhance osteogenic competence. TSA treatment increased expression of the epigenetic regulator KDM1B and was associated with activation of early epigenetic/lineage priming programs. Subsequent phenamil treatment increased BMP2 expression and enrichment of BMP-responsive signaling, consistent with activation of downstream osteogenic gene networks. Collectively, this dataset provides a molecular framework for how epigenetic modulation followed by pro-osteogenic signaling can cooperate to restore osteogenic differentiation capacity in senescent rMSCs.