Rab27a-mediated extracellular vesicle secretion contributes to osteogenesis in periodontal ligament-bone niche communication

Autor: Yun Lu, Liru Zhao, Jiaqi Mao, Wen Liu, Wensheng Ma, Bingjiao Zhao
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-023-35172-x
Popis: Abstract Periodontitis, an infectious and common disease worldwide, leads to the destruction of the periodontal ligament-alveolar bone complex. Within the bone metabolic niche, communication between periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMMSCs) has been considered a major contributor to osteogenesis. PDLSC-derived extracellular vesicles (P-EVs) have shown great potential for bone regeneration. However, the secretion and uptake mechanisms of P-EVs remain elusive. Herein, the biogenesis of extracellular vesicles (EVs) from PDLSCs was observed using scanning and transmission electron microscopy. PDLSCs were transduced with Ras-associated protein 27a (Rab27a) siRNA (PDLSC siRab27a ) to inhibit EV secretion. The effect of P-EVs on BMMSCs was evaluated using a non-contact transwell co-culture system. We observed that Rab27a knockdown decreased EV secretion, and PDLSC siRab27a remarkably attenuated co-culture-enhanced osteogenesis of BMMSCs. Isolated PDLSC-derived EVs enhanced osteogenic differentiation of BMMSCs in vitro and induced bone regeneration in a calvarial defect model in vivo. PDLSC-derived EVs were rapidly endocytosed by BMMSCs via the lipid raft/cholesterol endocytosis pathway and triggered the phosphorylation of extracellular signal-regulated kinase 1/2. In conclusion, PDLSCs contribute to the osteogenesis of BMMSCs through Rab27a-mediated EV secretion, thereby providing a potential cell-free approach for bone regeneration.
Databáze: Directory of Open Access Journals
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