Exosomal mRNAs/microRNAs in Osteogenesis and Bone Regeneration: From Signaling to Therapeutic Roles

Bone regeneration remains a significant clinical challenge in conditions such as trauma, osteoporosis, and aging-related bone loss. Recent advances have highlighted the crucial role of extracellular vesicles, especially exosomes, in intercellular signaling pathways that support bone homeostasis and repair. Among their bioactive cargoes, exosomal RNAs—particularly messenger RNAs and microRNAs—have emerged as central regulators of osteogenesis by modulating gene expression, cellular differentiation, and communication within the bone microenvironment. In this review, we provide a comprehensive summary of exosome biology, including their biogenesis, secretion, uptake mechanisms, and RNA cargo characteristics. We critically examine current evidence on how exosomal RNAs influence the molecular mechanisms of bone formation, remodeling, and regeneration under both physiological and pathological conditions such as fractures, diabetes, osteoporosis, and osteoarthritis. Furthermore, we discuss the emerging therapeutic potential of engineered exosomes as RNA delivery systems in bone tissue engineering and regenerative medicine. A better understanding of the functional roles and clinical relevance of exosomal RNAs may pave the way for next-generation, RNA-based therapies in skeletal repair and treatment of bone-related diseases. Impact Statement This review highlights the crucial role of exosomal mRNAs and microRNAs in regulating osteogenesis and bone regeneration. By elucidating the molecular mechanisms and signaling pathways involved, it provides new insights into the potential of exosome-based therapies in bone tissue engineering. This work may accelerate the development of innovative RNA-based regenerative strategies, ultimately improving treatment outcomes for bone diseases and injuries.