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Small Extracellular Vesicles Derived from Adipocytes Attenuate Intervertebral Disc Degeneration in Rats by Rejuvenating Senescent Nucleus Pulposus Cells and Endplate Cells by Delivering Exogenous NAMPT
Oxid Med Cell Longev. 2021 Aug 14;2021:9955448. doi: 10.1155/2021/9955448.
Yongjin Sun 1, Xu Li 1, Xiaoxu Yang 1, Bi Chen 2, Wenzhi Zhang 1
Abstract:
Cellular senescence is a key factor in the development of intervertebral disc degeneration (IVDD). Age-associated decreases in NAD+ levels play a critical role in regulating cellular senescence. Previous studies have found that small extracellular vesicles (sEVs) secreted by adipocytes (Adipo-sEVs) or adipose tissue are abundant in nicotinamide phosphoribosyltransferase (NAMPT), which is the key NAD+ biosynthetic enzyme in mammals. Systemic injection of these sEVs significantly improves physical activity and extends the lifespan of aged mice by increasing NAD+ levels. However, to date, the therapeutic potential of Adipo-sEVs in other age-associated disease models, such as IVDD, has not been explored. In this study, we investigated the therapeutic effects of Adipo-sEVs on senescence of nucleus pulposus cells (NPCs) and cartilaginous endplate cells (EPCs). In vitro, Adipo-sEVs could rejuvenate the senescence of NPCs and EPCs. Age-related dysfunctions were also ameliorated by Adipo-sEVs by delivering NAMPT and activating NAD+ biosynthesis and the Sirt1 pathway. Further in vivo experiments revealed that Adipo-sEV-mediated delivery of NAMPT attenuated IVDD in rats by rejuvenating senescent NPCs and EPCs. Collectively, the results indicate a new cell-free tool and provide a promising sEV-mediated delivery method of NAMPT as a therapeutic approach for IVDD clinically.
PMID: 34434488
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382538/