Post-Transcriptional Regulation of FGF Signaling: Insights from Musculoskeletal System

Fibroblast growth factor (FGF) signaling plays a pivotal role in the development, maintenance, and regeneration of musculoskeletal tissues. While its transcriptional regulation has been extensively characterized, accumulating evidence indicates that FGF activity is also modulated by a diverse array of post-transcriptional mechanisms. In this review, microRNAs, long non-coding RNAs, alternative splicing, and RNA modifications are examined as key regulators of FGF ligands and receptors across bone, cartilage, muscle, and tooth. Enhancer RNAs and RNA-binding proteins are also discussed as potential modulators of FGF transcript stability and translation. By integrating both established and emerging layers of RNA-level regulation, this review outlines a complex, tissue-specific architecture that fine-tunes FGF signaling in development and repair. To highlight this layered regulatory dimension, the concept of a pathway-specific RNA regulome is introduced, referring to the network of RNA-based mechanisms that modulate signaling cascades, such as FGF, across distinct biological processes. The therapeutic implications of targeting post-transcriptional nodes, particularly through non-coding RNAs and epitranscriptomic marks, are highlighted as promising avenues for future musculoskeletal interventions.