@article{Wang2023, 
author = {Yu Wang and Shanshan Jin and Dan Luo and Danqing He and Min Yu and Lisha Zhu and Zixin Li and Liyuan Chen and Chengye Ding and Xiaolan Wu and Tianhao Wu and Weiran Huang and Xuelin Zhao and Meng Xu and Zhengwei Xie and Yan Liu},
title = {Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells},
year = {2023},
journal = {Bone Research},
volume = {11},
pages = {54},
url = {https://www.sciopen.com/article/10.1038/s41413-023-00288-3},
doi = {10.1038/s41413-023-00288-3},
abstract = {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 the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy. Thus, the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.}
}