Systemic elimination of senescent cells using senolytic drugs presents
therapeutic effects on age-related diseases, including
senile osteoporosis. However, low bioavailability and potential side effects of
senolytics restrict clinical application. Therefore, we developed a bone-targeted delivery system for
senolytics to effective treatment of
senile osteoporosis. In this study,
quercetin was screened out as the ideal
senolytics for eliminating senescent BMSCs. Treatment of
quercetin efficiently decreased the senescence markers in senescent BMSCs models.
After treatment with
quercetin in vitro, cell mitosis and calcification staining assay confirmed that the proliferation and osteogenesis of the senescent BMSCs populations were enhanced. To enhance the effectiveness and minimize the side effect of treatment,
liposomes decorated with bone affinity
peptide (DSS)6 were constructed for bone-targeted delivery of
quercetin. After administration of
liposomes loading
quercetin in two aged mice models, histological and cellular analysis confirmed that bone-targeted treatment with
quercetin efficiently eliminated senescent cells in bone, restored the function of BMCSs, and promoted bone formation in aged mice models when compared to non-targeted treatment. Taken together, the bone-targeted delivery of
senolytics efficiently eliminates senescent cells to recover bone mass and microarchitecture, showing an effective treatment for
senile osteoporosis. STATEMENT OF SIGNIFICANCE:
Senile osteoporosis, a common and hazardous
chronic disease, has been still lacking effective
therapy. How to effectively eliminate the hazards of senescent cells in skeleton to bone formation remains challenge. In this study,
quercetin was screened out as the ideal senolytic
drug for senescent BMSCs and could effectively eliminated senescent BMSCs to restore the cellular functions of senescent BMSCs models in vitro. Then, the bone-targeted
liposomes were designed to encapsulate and deliver
senolytics efficiently to senile bone tissue. Based on two aged mice models, we confirmed that bone-targeted delivery of
quercetin efficiently eliminated senescent cells in skeleton and enhanced bone formation in vivo, suggesting the bone-targeted elimination of senescent cells is an effective treatment for
senile osteoporosis.