Reln mRNA Delivery Drives Neurogenic Bone Regeneration by Orchestrating Schwann Cell-Mediated Exosomal Trafficking.
Overview
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, Beijing, China
- Sydney Dental School, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Charles Perkins Centre, The University of Sydney, Camperdown, Australia
- School of Stomatology Sanya Division (Sanya Stomatology Center), Peking University, Sanya, Hainan, China
Abstract
Neurogenic bone regeneration is essential for the effective restoration of bone tissue functionality, while the mechanisms and new strategies underlying neurogenic bone regeneration remain to be further explored. Here, single‐cell transcriptomic analysis revealed enhanced mesenchymal‐Schwann cell crosstalk during bone regeneration. Functionally, we verify that Schwann cells are indispensable for bone regeneration via paracrine exosome‐mediated crosstalk with MSCs, a process promoted by Reelin. Mechanistically, Reelin enhances Schwann cell‐derived exosome internalization by MSCs via regulating exosomal proteins, especially UBE2K, which promotes MSC osteogenic differentiation through the ERK pathway, associated with Lys63‐linked polyubiquitination. For effective neurogenic bone regeneration, we engineered mesoporous silica nanoparticles (MSNs) as a CRISPRa delivery system for local Reln gene activation at the defect area. This mRNA delivery system could promote bone regeneration in both calvarial defect and tibial fracture models by constructing a pro‐osteogenic neurogenic microenvironment. Collectively, our findings uncover a Reelin‐Schwann cell exosomes‐ERK regulatory axis in bone regeneration with translational potential, highlighting the therapeutic value of targeting neural‐osteogenic crosstalk in bone regeneration.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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The paper's code and data availability statement is in the Data section.
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Data
Datasets cited
- geo:GSE245094, at NCBI GEO; found in the text, “Single‐Cell RNA Sequencing Data Processing and…”
Data Availability Statement
The bulk RNA seq data is deposited in the China National GeneBank (CNGB) Sequence Archive (CNSA) under the accession code: PRJCA058228. The mass spectrometry data is deposited in the PRoteomics IDEntifications Database (PRIDE) under the accession code: PXD077621. Other data that support the findings of this study are available from the corresponding author upon reasonable request.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 3 November 2026: the first record
Recorded: type, language, journal, pages, dates, 10 authors, 5 keywords, 3 funders, 59 references.
Cite
This paper
Lin, S., Li, Q., Liu, D., Li, M., Zhang, H., Chen, L., Yu, Y., Jiang, J., Xu, C., & Yang, R. (2026). Reln mRNA Delivery Drives Neurogenic Bone Regeneration by Orchestrating Schwann Cell-Mediated Exosomal Trafficking. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e78530. https://
BibTeX
@article{lin2026reln,
author = {Lin, Shuai and Li, Qianwen and Liu, Duo and Li, Mingzhao and Zhang, Han and Chen, Liujing and Yu, Yan and Jiang, Jiuhui and Xu, Chun and Yang, Ruili},
title = {{Reln mRNA Delivery Drives Neurogenic Bone Regeneration by Orchestrating Schwann Cell-Mediated Exosomal Trafficking}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = nov,
pages = {e78530},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/
url = {https://
pmid = {42969166},
pmcid = {PMC13725739}
}
RIS
TY - JOUR
AU - Lin, Shuai
AU - Li, Qianwen
AU - Liu, Duo
AU - Li, Mingzhao
AU - Zhang, Han
AU - Chen, Liujing
AU - Yu, Yan
AU - Jiang, Jiuhui
AU - Xu, Chun
AU - Yang, Ruili
TI - Reln mRNA Delivery Drives Neurogenic Bone Regeneration by Orchestrating Schwann Cell-Mediated Exosomal Trafficking
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/
SP - e78530
SN - 2198-3844
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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