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Apoptotic vesicles rejuvenate mesenchymal stem cells via Rab7-mediated autolysosome formation and alleviate bone loss in aging mice

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Abstract

Aging skeletons display decreased bone mass, increased marrow adiposity, and impaired bone marrow mesenchymal stem cells (MSCs). Apoptosis is a programmed cell death process that generates a large number of apoptotic vesicles (apoVs). Dysregulated apoptosis has been closely linked to senescence-associated diseases. However, whether apoVs mediate aging-related bone loss is not clear. In this study, we showed that young MSC-derived apoVs effectively rejuvenated the nuclear abnormalities of aged bone marrow MSCs and restored their impaired self-renewal, osteo-/adipo-genic lineage differentiation capacities via activating autophagy. Mechanistically, apoptotic young MSCs generated and enriched a high level of Ras-related protein 7 (Rab7) into apoVs. Subsequently, recipient aged MSCs reused apoV-derived Rab7 to restore autolysosomes formation, thereby contributing to autophagy flux activation and MSC rejuvenation. Moreover, systemic infusion of young MSC-derived apoVs enhanced bone mass, reduced marrow adiposity, and recused the impairment of recipient MSCs in aged mice. Our findings reveal the role of apoVs in rejuvenating aging-MSCs via restoring autolysosome formation and provide a potential approach for treating age-related bone loss.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 82170924), the National Key R&D Program of China (No. 2021YFA1100600), the Pearl River Talent Recruitment Program (Nos. 2019ZT08Y485 and 2019JC01Y138), the Guangdong Financial Fund for High-Caliber Hospital Construction (174-2018-XMZC-0001-03-0125, C-03 and D-11), the Sun Yat-sen University Young Teacher Key Cultivation Project (No. 18ykzd05).

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  1. Hospital of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, China

    Fangcao Lei, Zhiqing Huang, Qianmin Ou, Jiaqi Li, Manqing Liu, Lan Ma, Lingping Tan & Xiaoxing Kou

  2. Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, 510080, China

    Xiaoxing Kou

  3. Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China

    Zhengmei Lin

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  1. Fangcao Lei
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Apoptotic vesicles rejuvenate mesenchymal stem cells via Rab7-mediated autolysosome formation and alleviate bone loss in aging mice

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Lei, F., Huang, Z., Ou, Q. et al. Apoptotic vesicles rejuvenate mesenchymal stem cells via Rab7-mediated autolysosome formation and alleviate bone loss in aging mice. Nano Res. 16, 822–833 (2023). https://doi.org/10.1007/s12274-022-4709-4

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