1. Academic Validation
  2. Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors

Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors

  • Nat Commun. 2021 Oct 15;12(1):6043. doi: 10.1038/s41467-021-26302-y.
Wei Xia # 1 Jing Xie # 1 Zhiqing Cai # 1 Xuhua Liu 2 Jing Wen 3 Zhong-Kai Cui 1 Run Zhao 1 Xiaomei Zhou 1 Jiahui Chen 2 Xinru Mao 4 Zhengtao Gu 5 Zhimin Zou 5 Zhipeng Zou 1 Yue Zhang 1 Ming Zhao 5 Maegele Mac 6 Qiancheng Song 7 Xiaochun Bai 8
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 2 State Key Laboratory of Organ Failure Research, Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, 510630, China.
  • 3 Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 4 Department of Clinical laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 5 Department of Pathophysiology, Guangdong Provincial Key Laboratory of Shock and Microcirculation Research, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 6 Institute for Research in Operative Medicine, Private University of Witten-Herdecke, Cologne Merheim Medical Center, Ostmerheimerstr 200, D-51109, Cologne, Germany.
  • 7 Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 8 Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • # Contributed equally.
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.

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