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Original Article | Open Access

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

Yu Wang1, Shanshan Jin1, Dan Luo2, Danqing He1, Min Yu1, Lisha Zhu1, Zixin Li1, Liyuan Chen1, Chengye Ding1, Xiaolan Wu1, Tianhao Wu1, Weiran Huang3, Xuelin Zhao4, Meng Xu4, Zhengwei Xie3,( ), Yan Liu1, ( )
Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing 100081, China
CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China
Peking University International Cancer Institute, Health Science Center, Peking University, Beijing 100083, China
Department of Orthopedics, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China

These authors jointly supervised this work: Zhengwei Xie, Yan Liu

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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.

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Bone Research
Volume 11,
December 2023
Article number: 54
DOI: 10.1038/s41413-023-00288-3
Cite this article:
Wang Y, Jin S, Luo D, et al. Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells. Bone Research, 2023, 11: 54. https://doi.org/10.1038/s41413-023-00288-3

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Received: 01 July 2023
Revised: 16 August 2023
Accepted: 17 August 2023
Published: 23 October 2023
© The Author(s) 2023

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