MicroRNAs Play Key Roles in Progenitor Maintenance, Proliferation, and Osteogenic Differentiation of Osteogenic Progenitor Cells in Syndromic and Nonsyndromic Craniosynostosis

Craniosynostosis (CS) is a congenital birth defect defined by the premature closure of one or more cranial sutures. Approximately 70% of CS cases are nonsyndromic, with underlying causes frequently remaining unidentified. This study seeks to identify short noncoding RNAs, specifically microRNAs (miRNAs), associated with syndromic, nonsyndromic, and all forms of CS to advance understanding of its etiology. Through a systematic review, a total of 165 genes were identified as associated with human CS (112 syndromic, 37 nonsyndromic, and 13 overlapping). Bioinformatic analyses identified several miRNAs capable of regulating these CS-related genes. We found that miR-377 and miR-335-3p were specifically involved in the regulation of genes associated with syndromic CS, while miR-371-5p, miR-329, and miR-204-5p were specifically involved in gene regulation related to nonsyndromic CS. In contrast, miR-651-3p, miR-362-3p, and miR-425 play a role in both syndromic and nonsyndromic CS. Subsequent enrichment analysis using ShinyGO revealed that the predicted targets of these nine candidate miRNAs were preferentially enriched in the TGF-beta signaling pathway. Notably, functional modulation of these miRNAs altered the undifferentiated state, cell proliferation, and osteogenic differentiation of suture progenitor cells. Taken together, our study indicates that these miRNAs play a role in CS by changing the cell characteristics of suture progenitor cells.