Bioactive glass nanoparticle-induced osteogenesis via lncRNA Gm16263/Taok3 axis facilitates Gm16263-loaded EV bone regeneration therapy

Abstract

Bioactive glass nanoparticles (BGN) are potent osteogenic materials, but their capacity to regulate the non-coding genome, specifically long non-coding RNAs (lncRNAs), remains poorly understood. Here, we identified a novel lncRNA Gm16263 that was significantly upregulated in BGN-stimulated mesenchymal stem cells (MSCs) through transcriptomic profiling. Functional in vitro studies demonstrated that Gm16263 directly interacted with the kinase Taok3 and upregulated its expression, ultimately facilitating osteogenic differentiation of MSCs. Delivery of Gm16263 via MSC-derived extracellular vesicles (EVs) effectively mitigated bone loss in osteoporotic mice, and further significantly promoted bone repair in calvarial defect mice upon incorporation into a thermosensitive hydrogel. These therapeutic effects observably associated with upregulated Taok3 expression, further confirming the role of Gm16263/Taok3 axis in vivo. Collectively, our findings elucidated a crucial lncRNA regulatory mechanism underlying BGN-induced osteogenesis, thereby establishing a foundational framework for lncRNA-directed bone tissue engineering and highlighting the Gm16263/Taok3 axis as a promising target to treat bone disorders.