Scholarlink

<p>Intervertebral disc degeneration is a major cause of low back pain and is associated with inflammatory macrophages that promote annulus fibrosus degeneration via osteopontin signaling. Here we report an annulus fibrosus anchored nanovector carrying small interfering RNA targeting osteopontin. The nanovector first binds annulus fibrosus cells via a targeting peptide and is subsequently activated by reactive oxygen species in inflammatory microenvironments to release macrophage targeted hybrid nanovesicles. This sequential design enables local retention in disc tissue and subsequent delivery to osteopontin expressing macrophages. Using human single cell transcriptomic analysis, in vitro macrophage and annulus fibrosus cell coculture assays, mouse macrophage depletion and infiltration models, and rat disc injury models, we show that this strategy reduces pro inflammatory macrophage polarization, preserves extracellular matrix integrity, and improves disc structure. These findings support an inflammation responsive immunomodulatory approach for disc repair in preclinical models.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

An annulus fibrosus anchored nanovector reprograms osteopontin driven macrophages in preclinical disc degeneration models

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月21日

查看全文
  • Zilong Li,
  • Yucheng Xue,
  • Zhenyu Li,
  • Miaojie Fang,
  • Yiwen Xu,
  • Kelei Wang,
  • Hong Liu,
  • Zhenzhong Chen,
  • Jianbin Xu,
  • Ning Zhang

摘要

Intervertebral disc degeneration is a major cause of low back pain and is associated with inflammatory macrophages that promote annulus fibrosus degeneration via osteopontin signaling. Here we report an annulus fibrosus anchored nanovector carrying small interfering RNA targeting osteopontin. The nanovector first binds annulus fibrosus cells via a targeting peptide and is subsequently activated by reactive oxygen species in inflammatory microenvironments to release macrophage targeted hybrid nanovesicles. This sequential design enables local retention in disc tissue and subsequent delivery to osteopontin expressing macrophages. Using human single cell transcriptomic analysis, in vitro macrophage and annulus fibrosus cell coculture assays, mouse macrophage depletion and infiltration models, and rat disc injury models, we show that this strategy reduces pro inflammatory macrophage polarization, preserves extracellular matrix integrity, and improves disc structure. These findings support an inflammation responsive immunomodulatory approach for disc repair in preclinical models.