破骨细胞
骨质疏松症
骨吸收
肽
去卵巢大鼠
材料科学
体内
体内分布
药理学
医学
癌症研究
体外
内科学
生物化学
生物
生物技术
雌激素
作者
Yuyu Li,Shuqin Cao,Qiwen Li,Hanwen Li,Leixiao Yu,Bin Shao,Quan Yuan,Shujuan Zou,Chenchen Zhou
标识
DOI:10.1021/acsami.2c19632
摘要
Osteoporosis is a systemic skeletal disorder characterized by excessive osteoclastic bone resorption and impaired osteoblastic bone formation. Traditional delivery of antiresorptive drugs lacks a specific biodistribution in the body and may cause adverse effects to the patients. In this study, the peptide BTRM is first synthesized consisting of the bone-targeting peptide Asp8 (BT) and the peptide derived from the amino acid sequences of RANK Motif2/3 (RM), two cytoplasmic RANK motifs (PVQEET560-565 and PVQEQG604-609) that have been reported to play an important role in osteoclastogenesis. Then, BTRM is conjugated on the plant virus-like nanoparticles (VNPs) obtained from cowpea chlorotic mottle viruses (CCMVs), forming the engineered plant viruses BTRM-VNPs. In vitro experiments demonstrate that BTRM-VNPs can effectively and safely inhibit osteoclast differentiation and function. Moreover, after injection into ovariectomized mice, BTRM-VNPs show excellent capability to target bone tissue and improve osteoporotic bone loss. Collectively, the findings may provide a novel and promising strategy in the treatment of osteoporotic defects via targeting bone tissue and regulating the function of RANK Motif2/3.
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