异位骨化
肌腱
PLGA公司
医学
结缔组织
PI3K/AKT/mTOR通路
细胞生物学
癌症研究
病理
化学
信号转导
生物
解剖
生物化学
体外
作者
Yangwu Chen,Wei Shen,Chaoying Tang,Jichao Huang,Chunmei Fan,Zi Yin,Yin Hu,Weishan Chen,Yixi Zhou,Zhengwei Mao,Xiao Chen
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2020-05-01
卷期号:6 (18)
被引量:55
标识
DOI:10.1126/sciadv.aay9526
摘要
Heterotopic ossification (HO) in connective tissues like tendons and ligaments severely damages tissue structure. The pathogenesis of HO remains unclear but may involve mTOR. The results presented here indicate that tendon stem/progenitor cells do not undergo osteochondrogenic differentiation when mTOR signaling is inactivated by gene knockout or rapamycin (RAPA) treatment. Meanwhile, it is necessary to deliver RAPA to the injured sites and avoid disturbing the normal tendon. A RAPA delivery system, developed using collagen hybrid peptide (CHP) to modify the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, targeted RAPA specifically to pathological tendon collagen. The CHP-PLGA-RAPA nanoparticles showed excellent pathological collagen affinity, sustained-release ability, and bioactivity. In a mouse model of tendon HO, CHP-PLGA-RAPA nanoparticles specifically bound to pathological tendon and strongly suppressed HO progression. The mTOR signaling pathway appears to be a viable therapeutic target for tendon HO, and CHP-PLGA nanoparticles may be valuable for the treatment of tendon-related diseases.
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