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- Title
Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors.
- Authors
Xia, Wei; Xie, Jing; Cai, Zhiqing; Liu, Xuhua; Wen, Jing; Cui, Zhong-Kai; Zhao, Run; Zhou, Xiaomei; Chen, Jiahui; Mao, Xinru; Gu, Zhengtao; Zou, Zhimin; Zou, Zhipeng; Zhang, Yue; Zhao, Ming; Mac, Maegele; Song, Qiancheng; Bai, Xiaochun
- Abstract
Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3′UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats. Importantly, increased fibronectin expression on sEVs surface contributes to targeting of osteoprogenitors in bone by TBI sEVs, thereby implying that modification of the sEVs surface fibronectin could be used in bone-targeted drug delivery. Together, our work unveils a role of central regulation in bone formation and a clear link between injured neurons and osteogenitors, both in animals and clinical settings. Concomitant traumatic brain injury accelerates bone healing, but the mechanism is unclear. Here, the authors show that injured neurons, mainly those in the hippocampus, release osteogenic miRNA-enriched small extracellular vesicles, which targete osteoprogenitors to stimulate bone formation.
- Subjects
EXTRACELLULAR vesicles; BONE growth; HEALING; BRAIN injuries; HYDROGELS
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-26302-y