Transcriptomic signatures of osteogenic differentiation in human mesenchymal stem cells: A systematic review transcriptomics of osteogenic MSC differentiation

Background: The osteogenic differentiation of human mesenchymal stem cells (hMSCs) is foundational for bone tissue engineering. Transcriptional profiling has been carried out to characterize important genes and pathways determining osteoblast lineage commitment.
Purpose of Study: To synthesise recent transcriptomic evidence from 2020-2025 describing gene expression signature, active signalling pathways, cellular heterogeneity, and non-coding RNA regulation associated with the osteogenic differentiation of human MSCs.
Methodology: A structured search of relevant literature was made in PubMed and Scopus to identify peer-reviewed articles that used techniques of bulk RNA sequencing and single cell sequencing to analyse osteogenically induced human MSC cells.
Results: Overall, across all studies, the process of osteogenic differentiation was consistently linked to activation of the evolutionarily conserved transcription and expression profile centred on RUNX2, as well as upregulation of extracellular matrix-related genes and important signalling pathways for osteogenic differentiation, including Wnt/β-catenin and BMP/TGF-β pathways. Additionally, single-cell RNA studies suggest heterogeneity and transitional differentiation states across single-cell populations, indicating an asynchronous and lineage-primed process for osteogenic differentiation. Moreover, a significant regulatory effect was highlighted for non- coding RNAs, including microRNAs, circular RNAs, and long non-coding RNAs, on the osteogenic expression profile.
Conclusion: In recent studies of the transcriptome related to hMSCs, the overall molecular mechanism for the differentiation of these stem cells in bone tissue has been revealed to be conserved but dependent upon the tissue from where the MSCs were obtained and the analytical technique used for the determination of the differentiation potential of these stem cells.