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Research Article

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

Fangcao Lei1, Zhiqing Huang1, Qianmin Ou1, Jiaqi Li1, Manqing Liu1, Lan Ma1, Lingping Tan1, Zhengmei Lin3(), Xiaoxing Kou1,2()
Hospital of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China
Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou 510080, China
Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China
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Apoptotic vesicles (apoVs) were internalized and colocalized with lysosomes to activated autophagy via restoring autolysosome formation. Ras-related protein 7 (Rab7) enriched in apoVs could mediate the fusion of autophagosome and lysosome (autolysosome), then activate the arrested autophagy flux in senescent mesenchymal stem cells (MSCs) to promote the osteogenic differentiation and inhibit adipogenic differentiation.

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.

Keywords

apoptotic vesiclesmesenchymal stem cells (MSCs)autolysosome formationRas-related protein 7 (Rab7)aging

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Nano Research
Volume 16 Issue 1,
January 2023
Pages 822-833
DOI: 10.1007/s12274-022-4709-4
Cite this article:
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 Research, 2023, 16(1): 822-833. https://doi.org/10.1007/s12274-022-4709-4
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