Exosomes in bone health and disease: cellular crosstalk, systemic signaling, and AI-driven advances in regenerative therapy.

Exosomes have emerged as critical mediators of intercellular and inter-organ communication in bone biology. Secreted by bone-resident cells such as osteoblasts, osteoclasts, osteocytes, and mesenchymal stem cells (MSCs), these nanosized vesicles carry diverse molecular cargos that regulate bone remodeling, regeneration, and skeletal homeostasis. In addition to mediating local communication within the bone microenvironment, exosomes also participate in systemic crosstalk communication between bone and other tissues, including skeletal muscle, adipose tissue, gut microbiota, the immune system, the nervous system, and vasculature. Disruption of these exosome-mediated pathways contributes to the development and progression of bone diseases, including osteoporosis, osteoarthritis, osteonecrosis of the femoral head, and bone metastases. This review summarizes current advances in exosome-mediated signaling in both physiological and pathological contexts, with particular emphasis on their roles as biomarkers, therapeutic agents, and drug delivery vehicles. We also discuss the emerging contribution of artificial intelligence (AI) to exosome research, especially in biomarker discovery, disease classification, and target identification, as well as the major challenges that currently limit clinical translation. Together, these insights highlight the potential of exosome-based strategies for precision medicine in bone diseases.