Young BMSC-derived extracellular vesicles containing lncRNA sponging miR-1843a-5p to regulate Mob3a/YAP axis promote osteogenesis of senescent BMSCs

Bone repair in elderly patients poses a huge challenge due to the age-related progressive degenerative decline in regenerative abilities attributed to the senescence of bone marrow stem cells (BMSCs). Stem cell extracellular vesicles-mediated therapy are increasingly acknowledged as a promising strategy for delaying senescence and promoting osteogenesis. Osteoinductive exosome (OI-exo) derived from young BMSCs was applied to treatment of aging bone regeneration and demonstrated to alleviate aging-related phenotypes and promote proliferation and osteogenic differentiation of senescent BMSCs in vitro . OI-exo-loaded hierarchical mesoporous bioactive glass (MBG) scaffold was applied in calvarial defect of aged rats and induced rapid bone formation and efficient enhancement in osteogenesis in vivo , though excess activity of bone resorption in senescent individuals remained a tremendous challenge in aged bone regeneration. The potential underlying mechanism of young extracellular vesicles-enhanced osteogenesis of old BMSCs was revealed that OI-exos were rich in lncRNA-ENSRNOG00000056625, which functioned as a promoter of YAP dephosphorylation and nuclear translocation, ultimately resulting in elevated proliferation and osteogenic differentiation and reduced senescence-related phenotypes. The findings herein revealed the competing endogenous RNA network lncRNA-ENSRNOG00000056625/miR-1843a-5p/Mob3a, and might provide novel insights into the extracellular vesicles-stimulated osteogenesis and the downstream YAP signaling as a potential critical pathway in aging bone regeneration.