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Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration capacity via rejuvenating senescent tendon stem/progenitor cells

ABSTRACT: Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration capacity via rejuvenating senescent tendon stem/progenitor cells

PROVIDER: PRJNA1006711 | ENA |

REPOSITORIES: ENA

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Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration capacity via rejuvenating senescent tendon stem/progenitor cells [DMSO-treated and POG-treated TSPCs]

Project description:Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC- senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore self-renewal and proliferation capacities, and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescues endogenous tendon regeneration and repair capacity in aged rats to levels similar to normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and downregulating mTOR signaling with induction of autophagy. Together, the strategy by pharmacological intervention with deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons. We performed mRNA microarray analyses of DMSO-treated and POG-treated TSPCs from 18-month-old rats and identified meaningful genes in down-regulated and up-regulated group

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