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Senolytic controls bone marrow mesenchymal stem cells fate improving bone formation.

Dianying Zhang1, Kai Yu2, Jie Yang2

  • 1Department of Orthopedics and Trauma, People's Hospital, Peking University Beijing 100044, China.

American Journal of Translational Research
|July 14, 2020
PubMed
Summary

Eliminating senescent bone marrow mesenchymal stem cells (BMSCs) with quercetin improves their proliferation and bone formation while reducing fat production. This offers a new therapeutic strategy for treating osteoporosis.

Keywords:
Senolyticbone marrow mesenchymal stem cellsosteoporosisquercetinsenescence

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Area of Science:

  • Stem Cell Biology
  • Gerontology
  • Orthopedics

Background:

  • Osteoporosis is linked to aging, characterized by increased marrow fat and reduced bone formation.
  • Bone marrow mesenchymal stem cells (BMSCs) are crucial for bone health, and their senescence is implicated in osteoporosis.
  • Targeting BMSC senescence presents a potential therapeutic avenue for osteoporosis.

Purpose of the Study:

  • To investigate the effect of senolytics on regulating the differentiation of senescent BMSCs.
  • To determine if quercetin, a senolytic agent, can modulate BMSC fate.
  • To explore quercetin's impact on BMSC proliferation, migration, osteogenesis, and adipogenesis.

Main Methods:

  • Rat BMSCs were isolated and characterized.
  • Senescent BMSCs were treated with quercetin.
  • Cell proliferation was assessed using CCK-8 and colony formation assays.
  • Cell migration was evaluated via scratch wound healing and Transwell assays.
  • Osteogenic and adipogenic differentiation potentials were determined.

Main Results:

  • Quercetin treatment cleared senescent BMSCs, enhancing BMSC proliferation.
  • Cellular migration remained unaffected by quercetin treatment.
  • Osteogenic potential increased, while adipogenic potential decreased after senescent BMSC removal.
  • BMSCs demonstrated stemness characteristics.

Conclusions:

  • Clearing senescent BMSCs improves their proliferative and osteogenic capacities.
  • Inhibition of adipogenesis in BMSCs was observed after senescent cell removal.
  • Targeting senescent BMSCs with agents like quercetin offers a novel therapeutic approach for osteoporosis.