ESPE Yearbook of Paediatric Endocrinology

Frontiers in Endocrinology, (2025). 16, 1530374. https://doi.org/10.3389/fendo.2025.1530374

Brief Summary:This review explores the critical role of microRNAs (miRNAs) in regulating gene expression within the growth plate, which is a key structure for longitudinal bone growth. It discusses the mechanisms by which miRNAs such as miR-140, miR-1 and miR-26b influence the proliferation, differentiation and hypertrophy of chondrocytes, and emphasises their potential for use in the treatment of skeletal disorders such as idiopathic short stature and physeal injuries. The article emphasises recent advances in miRNA-based therapeutics and delivery systems, suggesting promising avenues for targeted skeletal repair.

Commentary: This review sheds light on the role of microRNAs (miRNAs) in modulating growth plate dynamics, which are fundamental to paediatric skeletal development. The authors chart how miRNAs such as miR-140, miR-1 and miR-26b act as molecular rheostats, fine-tuning gene expression during chondrocyte maturation and influencing key pathways such as PTHrP-IHH, BMP and WNT signalling. The clinical implications are significant: miR-140 mutations have been linked to human skeletal dysplasia, while miR-26b-3p is emerging as a potential biomarker and therapeutic target in idiopathic short stature. The review also highlights the development of miRNA-based therapies that could be used to prevent or repair physeal bony bridge formation, a challenging paediatric complication. The discussion of delivery challenges in dense, avascular cartilage and innovations such as cartilage-penetrating nanoparticles and exosome-based systems provides a realistic perspective on the therapeutic potential.