Molecular Signaling Pathways and MicroRNAs in Bone Remodeling: A Narrative Review

Bone remodeling is an intricate process executed throughout one's whole life via the cross-talk of several cellular events, progenitor cells and signaling pathways. It is an imperative mechanism for regaining bone loss, recovering damaged tissue and repairing fractures. To achieve this, molecular signaling pathways play a central role in regulating pathological and causal mechanisms in different diseases. Similarly, microRNAs (miRNAs) have shown promising results in disease management by mediating mRNA targeted gene expression and post-transcriptional gene function. However, the role and relevance of these miRNAs in signaling processes, which regulate the delicate balance between bone formation and bone resorption, are unclear. This review aims to summarize current knowledge of bone remodeling from two perspectives: firstly, we outline the modus operandi of five major molecular signaling pathways, i.e.,the receptor activator of nuclear factor kappa-B (RANK)-osteoprotegrin (OPG) and RANK ligand (RANK-OPG-RANKL), macrophage colony-stimulating factor (M-CSF), Wnt/β-catenin, Jagged/Notch and bone morphogenetic protein (BMP) pathways in regards to bone cell formation and function; and secondly, the miRNAs that participate in these pathways are introduced. Probing the miRNA-mediated regulation of these pathways may help in preparing the foundation for developing targeted strategies in bone remodeling, repair and regeneration.