The Golgi apparatus receives relatively little attention in the context of aging, but it suffers dysfunction like all structures in the cell. It is involved in directing newly manufactured proteins to their destination, whether inside the cell or to be secreted in extracellular vesicles. Researchers here show that extracellular vesicles harvested from a particular form of stem cell culture can act to improve Golgi apparatus function in aged tissues, and in doing so aid in improving bone density and bone regeneration in aged mice.
The production of stem cell aggregates (CA) is a regenerative technique that promotes normal stem cell function by encouraging high-density stem cells to secrete large amounts of extracellular matrix (ECM), which serves as an excellent cellular scaffold. Our previous studies have further revealed that CA-derived extracellular vesicles (CA-EVs) are featured with proteins that effectively promote tissue/organ regeneration.
In this study, we investigated the mechanisms underlying bone marrow mesenchymal stem cell (BMSCs) senescence in bone aging and explored whether CA-EVs can improve bone mass and regeneration with the advanced age. Surprisingly, we discovered that alterations of Golgi apparatus contributed to senescence of resident BMSCs and led to a reduction in the release of endogenous EVs, which has not been previously reported. We further found that locally transplanted CA lost its ability to promote bone regeneration in the aging microenvironment, which was also attributed to impaired structure and function of Golgi.
Intriguingly, in-depth analysis suggested that CA-EVs exposed functional surface proteins to assemble the Golgi apparatus, such as Syntaxin 5 (STX5), which helped restore function of senescent BMSCs. Importantly, CA-EV replenishment promoted regeneration of bone defects and counteracted osteoporosis in aging mice. These findings provide the first evidence that Golgi-based vesicular disorders contribute to cell senescence and that CA-EVs effectively mitigate BMSC aging to retard age-related osteoporosis and safeguard aging bone regeneration.
Link: https://doi.org/10.1038/s41413-024-00386-w
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