MicroRNAs regulate viability, longevity and extracellular matrix secretions of mesenchymal stem cell-derived...

Chondrogenic differentiation of human adipose tissue-derived mesenchymal stem cells (ADMSCs) is a promising strategy for cartilage regeneration, but its regulatory mechanisms remain incompletely understood. MicroRNAs (miRNAs) play critical roles in post-transcriptional control of lineage commitment and tissue development. This study aimed to identify miRNAs differentially expressed during ADMSCs chondrogenesis and explore their functional roles in chondrogenic gene regulation.

ADMSCs were induced to undergo chondrogenic differentiation under defined conditions. miRNA expression profiles were analyzed, and significantly dysregulated miRNAs were identified. Bioinformatic and literature-based analyses were used to associate these miRNAs with chondrogenic transcription factors, signaling pathways, and cellular processes.

Chondrogenesis was associated with distinct patterns of miRNA regulation. miR-140-5p, miR-520d-5p, miR-127-5p, and miR-218-5p were upregulated and correlated with increased expression of cartilage markers (SOX9, COL2A1, ACAN) and suppression of hypertrophy. These miRNAs were linked to TGF-β signaling, epigenetic regulation, and inhibition of terminal differentiation. Conversely, miR-145-5p, miR-101-3p, miR-194-5p, miR-199a-5p, miR-182-5p, miR-29a-5p, miR-20a-5p, miR-193b-5p, and miR-574-3p were downregulated, potentially relieving repression of transcription factors, signaling components, autophagy-related genes, and extracellular matrix regulators.

Chondrogenic differentiation of ADMSCs is governed by coordinated miRNA regulation, involving activation of pro-chondrogenic miRNAs and suppression of inhibitory ones. This regulatory network integrates key molecular pathways required for stable cartilage formation and highlights potential targets for improving ADMSCs-based regenerative therapies.