Stomatology ›› 2026, Vol. 46 ›› Issue (5): 321-329.doi: 10.13591/j.cnki.kqyx.2026.05.001

• Basic and Clinical Research •     Next Articles

Study on ursolic acid ameliorating osteoporosis by alleviating senescence of bone marrow mesenchymal stem cells

SUN Xueyu1,2,3, ZHAO Weiye1,2,3, ZHANG Kejia1,2,3, CAO Dan1,2,3, ZHANG Hanwen4,5,6(), YAN Bin1,2,3()   

  1. Department of OrthodonticsThe Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029, China
  • Received:2026-01-05 Online:2026-05-28 Published:2026-05-15

Abstract:

Objective To investigate whether ursolic acid (UA) can ameliorate osteoporosis-related jaw bone injuries by alleviating the senescence of bone marrow mesenchymal stem cells (BMMSCs). Methods An ovariectomized osteoporotic mouse model was established. After UA intervention,Micro-CT was used to evaluate the trabecular microstructure of the femur and jaw bone. Integrated multidatabase analysis,KEGG pathway enrichment,the CellAge database,and machine learning methods were employed to screen key senescence-related genes through which UA exerts its effects on osteoporosis. Based on single cell transcriptomic data from osteoporotic bone,the expression profiles of these key genes across different cell types were analyzed,and senescence scores for distinct cell populations were calculated using the SenMayo senescence-associated gene set. In vitro,BMMSCs were induced to senesce by H2O2 and then treated with UA. Senescence phenotypes and osteogenic capacity were assessed through SA-β-gal staining,ALP/ARS staining,and RT-PCR. Results Micro-CT analysis demonstrated that UA significantly improved trabecular bone micro-architecture in both the femur and jaw of osteoporotic mice. Bioinformatics analyses revealed that the potential targets of UA in osteoporosis were significantly enriched in the p53 signaling pathway and cellular senescence-related pathways. Single-cell transcriptomic analysis showed that multiple key senescence-related genes were expressed in BMMSCs,and senescence scoring based on the SenMayo gene set consistently indicated a higher level of senescence in BMMSCs from osteoporotic samples. Experiments further demonstrated that UA significantly alleviated hydrogen peroxide-induced senescent phenotypes in BMMSCs. Conclusion UA can ameliorate osteoporosis-associated bone injuries by alleviating senescence in BMMSCs,thereby exhibiting a potential bone-protective effect on the jaw.

Key words: ursolic acid, osteoporosis, jaw bone, bone marrow mesenchymal stem cells, cellular senescence

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