Decoding Noncoding RNAs: Mastering Bone Morphogenetic Protein Signaling and Crosstalk Pathways for Breakthroughs in Periodontal Regeneration.

Abstract

Regenerating periodontal tissues remains a significant hurdle in regenerative dentistry, requiring meticulous coordination of cellular and molecular mechanisms. Noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, are emerging as essential modulators of bone morphogenetic protein (BMP) signaling pathways, which are vital for processes such as osteogenesis, cementum formation, and periodontal ligament (PDL) repair. This review delves into the pivotal role of ncRNAs in influencing BMP signaling while briefly addressing their interaction with other critical pathways, such as transforming growth factor-beta, Activin, Wnt, Notch, mitogen-activated protein kinase, and PI3K. These ncRNAs act as dynamic regulators, fine-tuning BMP signaling to facilitate tissue differentiation, modulate inflammatory responses, and enhance extracellular matrix remodeling-key elements for addressing the complexity of periodontal tissue regeneration. By compiling the latest advancements, this review sheds light on the potential of ncRNAs as therapeutic targets, emphasizing their ability to refine BMP signaling for greater precision in tissue engineering. Moreover, the integration of ncRNA insights with advanced biomaterials and engineering solutions offers a promising direction for reconstructing the intricate bone-PDL-cementum complex. Framing ncRNAs as a central innovation in regenerative therapy, this review underscores their transformative potential in addressing the multifactorial challenges of periodontal repair and restoration.