Dataset Information

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

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.

SUBMITTER: Lu Y

PROVIDER: S-EPMC10213006 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Lu Yun Y Zhao Liru L Mao Jiaqi J Liu Wen W Ma Wensheng W Zhao Bingjiao B

Scientific reports 20230525 1

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. ...[more]

PMID: 37231020

Similar Datasets

Project description:BackgroundExtracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments. Given their boundary location, we propose ECs use bidirectional release of distinct EV cargo in quiescent (healthy) and activated (atheroprone) states to communicate with cells within the circulation and blood vessel wall.MethodsEVs were isolated from primary human aortic ECs (plate and transwell grown; ±IL [interleukin]-1β activation), quantified, visualized, and analyzed by miRNA transcriptomics and proteomics. Apical and basolateral EC-EV release was determined by miRNA transfer, total internal reflection fluorescence and electron microscopy. Vascular reprogramming (RNA sequencing) and functional assays were performed on primary human monocytes or smooth muscle cells±EC-EVs.ResultsActivated ECs increased EV release, with miRNA and protein cargo related to atherosclerosis. EV-treated monocytes and smooth muscle cells revealed activated EC-EV altered pathways that were proinflammatory and atherogenic. ECs released more EVs apically, which increased with activation. Apical and basolateral EV cargo contained distinct transcriptomes and proteomes that were altered by EC activation. Notably, activated basolateral EC-EVs displayed greater changes in the EV secretome, with pathways specific to atherosclerosis. In silico analysis determined compartment-specific cargo released by the apical and basolateral surfaces of ECs can reprogram monocytes and smooth muscle cells, respectively, with functional assays and in vivo imaging supporting this concept.ConclusionsDemonstrating that ECs are capable of polarized EV cargo loading and directional EV secretion reveals a novel paradigm for endothelial communication, which may ultimately enhance the design of endothelial-based therapeutics for cardiovascular diseases such as atherosclerosis where ECs are persistently activated.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets