SHED-derived exosomes ameliorate age-related osteoporosis by activating mitophagy in senescent bone marrow mesenchymal stem cells
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This study aims to explore the therapeutic efficacy of stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-Exo) in age-related osteoporosis (OP) and clarify its mechanism via mitophagy activation in senescent bone marrow mesenchymal stem cells (BMSCs). SHED-Exo were isolated, characterized and proteomically profiled. <i>In vitro</i>, H<sub>2</sub>O<sub>2</sub>-induced senescent bone marrow mesenchymal stem cells (BMSCs) were treated with SHED-Exo, with mitophagy modulators used for mechanistic validation. <i>In vivo</i>, SHED-Exo were systemically administered to aged osteoporotic mice, assessing biodistribution, safety and therapeutic effects via micro-computed tomography, and molecular analyses of bone tissue/BMSCs. SHED-Exo possessed canonical exosomal properties and were enriched in osteogenic/mitophagic proteins. <i>In vitro</i>, SHED-Exo restored mitochondrial function, activated mitophagy and enhanced osteogenic differentiation of senescent BMSCs. <i>In vivo</i>, SHED-Exo showed no organ toxicity and effectively ameliorated bone loss by upregulating mitophagic/osteogenic markers in aged osteoporotic mice. SHED-Exo ameliorate age-related OP by activating mitophagy in senescent BMSCs, serving as a novel translational nanotherapeutic for age-related bone disorders.
