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Bone-Targeted delivery of senolytics to eliminate senescent cells increases bone formation in senile osteoporosis
Xiaotao Xing 1, Qi Tang 2, Jiaojiao Zou 1, Haisen Huang 3, Jian Yang 3, Xin Gao 3, Xun Xu 3, Shixing Ma 3, Maojiao Li 3, Cheng Liang 3, Lin Tan 3, Li Liao 4, Weidong Tian 5
...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.