Investigating the Role of MicroRNAs in Mesenchymal Stem Cell Osteogenic Differentiation.

Mesenchymal stem cells (MSCs) are multipotent progenitors that give rise to osteoblasts, which are essential for bone formation, remodeling, and skeletal homeostasis. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as critical post-transcriptional regulators of gene expression that fine-tune MSC commitment, osteoblast proliferation, and matrix mineralization. In this review, we first summarize the physiological mechanisms of bone remodeling and the differentiation of MSCs into osteoblasts, with particular attention to the coordinated roles of osteoblasts, osteoclasts, and osteocytes. We then discuss how specific miRNAs regulate osteoblast growth and maturation by targeting key transcription factors such as Runx2 and osterix, as well as major signaling pathways including BMP and Wnt. Building on this mechanistic framework, we examine the contribution of dysregulated miRNAs to metabolic bone diseases, with a focus on osteoporosis, where alterations in age-related, hormonal, and inflammatory environments reshape miRNA networks and favor bone loss. Current and emerging clinical applications of miRNAs are also reviewed, including their use as minimally invasive circulating biomarkers for fracture risk assessment and treatment monitoring, and as therapeutic targets or tools through miRNA mimics and inhibitory agents. Finally, we highlight future perspectives that involve integrated analysis of miRNAs and other non-coding RNAs, advanced profiling approaches such as single-cell RNA sequencing, and miRNA-guided strategies for bone tissue regeneration. A comprehensive understanding of these regulatory networks is expected to support the development of more precise diagnostic tools and targeted therapies for osteoporosis and related skeletal disorders.