国内团队：骨靶向外泌体递送药物可缓解IBD相关骨质流失
- ①结肠炎小鼠的骨量及骨质量显著降低，股骨的骨形成率降低且成骨细胞减少；
- ②结肠炎小鼠的BMSC更倾向于分化成脂肪细胞（而非成骨细胞），而IBD患者的血清可促进人BMSC分化成脂肪细胞；
- ③机制上，结肠炎导致BMSC的Wnt信号下调；
- ④构建表面表达GLG1（通过与E-selectin结合实现骨靶向）且内部装载Wnt激动剂1的外泌体，静脉注射后可在骨中累积，并可缓解结肠炎小鼠的骨质流失，促进骨形成，加速骨折后的愈合。
主编推荐语
系统性骨质流失是IBD的常见并发症。上海大学及上海长海医院的苏佳灿团队、陈晓团队与徐灿团队在Cell Reports Medicine上发表的一项最新研究结果，Wnt信号下调导致结肠炎小鼠及IBD患者的骨髓间充质干细胞/基质细胞（BMSC）更倾向于分化成脂肪细胞（而非成骨细胞），从而抑制骨形成并促进骨质流失。构建携带Wnt激动剂的骨靶向外泌体，可在骨中累积，并缓解结肠炎小鼠的骨质流失。
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Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases
基于外泌体的骨靶向药物递送缓解IBD中的成骨细胞骨形成受损及骨质流失
10.1016/j.xcrm.2022.100881
01-04, Article
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Systematic bone loss is commonly complicated with inflammatory bowel diseases (IBDs) with unclear pathogenesis and uncertain treatment. In experimental colitis mouse models established by dextran sulfate sodium and IL-10 knockout induced with piroxicam, bone mass and quality are significantly decreased. Colitis mice demonstrate a lower bone formation rate and fewer osteoblasts in femur. Bone marrow mesenchymal stem/stromal cells (BMSCs) from colitis mice tend to differentiate into adipocytes rather than osteoblasts. Serum from patients with IBD promotes adipogenesis of human BMSCs. RNA sequencing reveals that colitis downregulates Wnt signaling in BMSCs. For treatment, exosomes with Golgi glycoprotein 1 inserted could carry Wnt agonist 1 and accumulate in bone via intravenous administration. They could alleviate bone loss, promote bone formation, and accelerate fracture healing in colitis mice. Collectively, BMSC commitment in inflammatory microenvironment contributes to lower bone quantity and quality and could be rescued by redirecting differentiation toward osteoblasts through bone-targeted drug delivery.
First Authors:
Jiawei Guo,Fuxiao Wang,Yan Hu
Correspondence Authors:
Can Xu,Xiao Chen,Jiacan Su
All Authors:
Jiawei Guo,Fuxiao Wang,Yan Hu,Ying Luo,Yan Wei,Ke Xu,Hao Zhang,Han Liu,Lumin Bo,Shunli Lv,Shihao Sheng,Xinchen Zhuang,Tao Zhang,Can Xu,Xiao Chen,Jiacan Su
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