Mesenchymal stem/stromal cells-derived exosomal miRNA delivery enhances bone repair in osteoporotic conditions

Developing effective therapeutic strategies to enhance bone repair under osteoporotic conditions remains a major clinical challenge. Increasing evidence indicates that aberrant lineage commitment of mesenchymal stem cells (MSCs) resident in bone marrow contributes to osteoporosis-related bone loss.

However, incomplete understanding of the regulatory mechanisms governing MSC differentiation has limited the development of efficient therapeutic approaches. In this study, we identified microRNA-423 (miR-423) as a negative regulator of osteogenic differentiation, and demonstrated that inhibition of miR-423 significantly enhanced osteoblast differentiation of MSCs. To enable in vivo delivery of the miR-423 inhibitor for bone repair, MSC-derived exosomes (MSC-Exo) were employed as a delivery vehicle, generating Exo–miR-423 inhibitor construct.