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

Yun Lu; Liru Zhao; Jiaqi Mao; Wen Liu; Wensheng Ma; Bingjiao Zhao

doi:10.1038/s41598-023-35172-x

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

Sci Rep. 2023 May 25;13(1):8479. doi: 10.1038/s41598-023-35172-x.

Authors

Yun Lu^#^{1

2}, Liru Zhao^#³, Jiaqi Mao³, Wen Liu², Wensheng Ma⁴, Bingjiao Zhao^{5

6}

Affiliations

¹ Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200001, China.
² Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China.
³ Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, 050017, China.
⁴ Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, 050017, China. wsma02@hebmu.edu.cn.
⁵ Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200001, China. joyce_zhao_ortho@fudan.edu.cn.
⁶ Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China. joyce_zhao_ortho@fudan.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Cells, Cultured
Communication
Extracellular Vesicles*
Humans
Osteogenesis*
Periodontal Ligament
Stem Cells / metabolism

Substances

RAB27A protein, human