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Objective:  Articular cartilage injury is common and difficult to treat clinically because of the characteristics of the cartilage. Bone marrow-derived mesenchymal stem cell (BMSC)-mediated cartilage regeneration is a promising therapy for treating articular cartilage injury. BMSC differentiation is controlled by numerous molecules and signaling pathways in the microenvironment at both the transcriptional and post-transcriptional levels. However, the possible function of super enhancer long non-coding RNAs (SE-lncRNAs) in the chondrogenic differentiation of BMSCs is still unclear. Our intention was to explore the expression profile of SE-lncRNAs and potential target genes regulated by SE-lncRNAs during chondrogenic differentiation in BMSCs.   Materials and Methods:  In this study, we conducted a human Super-Enhancer LncRNA Microarray to investigate the differential expression profile of SE-lncRNAs and mRNAs during chondrogenic differentiation of BMSCs. Subsequent bioinformatic analysis was performed to clarify the important signaling pathways, SE-lncRNAs, and mRNAs associated with SE-lncRNAs regulating the chondrogenic differentiation of BMSCs.   Results:  A total of 77 SE-lncRNAs were identified, of which 47 were upregulated and 30 were downregulated during chondrogenic differentiation. A total of 308 mRNAs were identified, of which 245 were upregulated and 63 were downregulated. Some pathways, such as focal adhesion, extracellular matrix (ECM)–receptor interaction, transforming growth factor-β (TGF-β) signaling pathway, and PI3K–Akt signaling pathway, were identified as the key pathways that may be implicated in the chondrogenic differentiation of BMSCs. Moreover, five potentially core regulatory mRNAs (PMEPA1, ENC1, TES, CDK6, and ADIRF) and 37 SE-lncRNAs in chondrogenic differentiation were identified by bioinformatic analysis.   Conclusion:  We assessed the differential expression levels of SE-lncRNAs and mRNAs, along with the chondrogenic differentiation of BMSCs. By analyzing the interactions and co-expression, we identified the core SE-lncRNAs and mRNAs acting as regulators of the chondrogenic differentiation potential of BMSCs. Our study also provided novel insights into the mechanism of BMSC chondrogenic and cartilage regeneration.

frontiers in cell and developmental biology

A Comprehensive Analysis of SE-lncRNA/mRNA Differential Expression Profiles During Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells