摘要
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 agingrelated 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.
基金
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).
