Cargando…

Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway

Recent studies have shown that co-culture systems play an important role in bone tissue engineering. In this study, human dental pulp stem cells (hDPSCs) were co-cultured with human adipose-derived stem cells (hADSCs), and osteoblastic phenotypes were found to be enhanced in co-cultures compared wit...

Descripción completa

Detalles Bibliográficos
Autores principales: Jin, Qiaoqiao, Li, Peilun, Yuan, Keyong, Zhao, Fen, Zhu, Xiaohan, Zhang, Pengfei, Huang, Zhengwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716067/
https://www.ncbi.nlm.nih.gov/pubmed/33312494
http://dx.doi.org/10.1177/2041731420975569
_version_ 1783619098439057408
author Jin, Qiaoqiao
Li, Peilun
Yuan, Keyong
Zhao, Fen
Zhu, Xiaohan
Zhang, Pengfei
Huang, Zhengwei
author_facet Jin, Qiaoqiao
Li, Peilun
Yuan, Keyong
Zhao, Fen
Zhu, Xiaohan
Zhang, Pengfei
Huang, Zhengwei
author_sort Jin, Qiaoqiao
collection PubMed
description Recent studies have shown that co-culture systems play an important role in bone tissue engineering. In this study, human dental pulp stem cells (hDPSCs) were co-cultured with human adipose-derived stem cells (hADSCs), and osteoblastic phenotypes were found to be enhanced in co-cultures compared with monocultures of hDPSCs or hADSCs. Furthermore, GW4869, an inhibitor of extracellular vesicle (EV) formation, suppressed the mineralization of co-cultured cells. Studies indicate that the therapeutic potential of DPSCs is realized through paracrine action, in which EVs play an important role. To study their role, we successfully obtained and identified hDPSC-derived extracellular vesicles (hDPSC-EVs), and further investigated their effects on hADSCs and the underlying mechanism. hADSCs were stimulated with hDPSC-EVs, which were found to promote the migration and mineralization of hADSCs. Moreover, hDPSC-EVs promoted osteogenic differentiation by enhancing the phosphorylation of ERK 1/2 and JNK in hADSCs. To investigate the specific proteins in EVs that might play a role in hADSC osteogenic differentiation, we performed proteomic analysis of hDPSC-EVs. We determined the top 30 enriched pathways, which notably included the insulin signaling pathway. The number of genes enriched in the insulin signaling pathway was the largest, in addition to the “protein processing in endoplasmic reticulum” term. The MAPK cascade is a typical downstream pathway mediating insulin signaling. To further study the effects of hDPSC-EVs on maxillofacial bone regeneration, we used hDPSC-EVs as a cell-free biomaterial in a model of mandibular defects in rats. To assess the therapeutic potential of EVs, we analyzed their proteome. Animal experiments demonstrated that hDPSC-EVs promoted the regeneration of bone defects. Overall, these results highlight the potential of hDPSC-EVs to induce lineage specific differentiation of hADSCs. The results also indicated the importance of considering hDPSC-EVs as biomimetic materials for clinical translation of treatments for oral maxillofacial defects.
format Online
Article
Text
id pubmed-7716067
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-77160672020-12-10 Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway Jin, Qiaoqiao Li, Peilun Yuan, Keyong Zhao, Fen Zhu, Xiaohan Zhang, Pengfei Huang, Zhengwei J Tissue Eng Original Article Recent studies have shown that co-culture systems play an important role in bone tissue engineering. In this study, human dental pulp stem cells (hDPSCs) were co-cultured with human adipose-derived stem cells (hADSCs), and osteoblastic phenotypes were found to be enhanced in co-cultures compared with monocultures of hDPSCs or hADSCs. Furthermore, GW4869, an inhibitor of extracellular vesicle (EV) formation, suppressed the mineralization of co-cultured cells. Studies indicate that the therapeutic potential of DPSCs is realized through paracrine action, in which EVs play an important role. To study their role, we successfully obtained and identified hDPSC-derived extracellular vesicles (hDPSC-EVs), and further investigated their effects on hADSCs and the underlying mechanism. hADSCs were stimulated with hDPSC-EVs, which were found to promote the migration and mineralization of hADSCs. Moreover, hDPSC-EVs promoted osteogenic differentiation by enhancing the phosphorylation of ERK 1/2 and JNK in hADSCs. To investigate the specific proteins in EVs that might play a role in hADSC osteogenic differentiation, we performed proteomic analysis of hDPSC-EVs. We determined the top 30 enriched pathways, which notably included the insulin signaling pathway. The number of genes enriched in the insulin signaling pathway was the largest, in addition to the “protein processing in endoplasmic reticulum” term. The MAPK cascade is a typical downstream pathway mediating insulin signaling. To further study the effects of hDPSC-EVs on maxillofacial bone regeneration, we used hDPSC-EVs as a cell-free biomaterial in a model of mandibular defects in rats. To assess the therapeutic potential of EVs, we analyzed their proteome. Animal experiments demonstrated that hDPSC-EVs promoted the regeneration of bone defects. Overall, these results highlight the potential of hDPSC-EVs to induce lineage specific differentiation of hADSCs. The results also indicated the importance of considering hDPSC-EVs as biomimetic materials for clinical translation of treatments for oral maxillofacial defects. SAGE Publications 2020-12-02 /pmc/articles/PMC7716067/ /pubmed/33312494 http://dx.doi.org/10.1177/2041731420975569 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Jin, Qiaoqiao
Li, Peilun
Yuan, Keyong
Zhao, Fen
Zhu, Xiaohan
Zhang, Pengfei
Huang, Zhengwei
Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway
title Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway
title_full Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway
title_fullStr Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway
title_full_unstemmed Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway
title_short Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway
title_sort extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the mapk pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716067/
https://www.ncbi.nlm.nih.gov/pubmed/33312494
http://dx.doi.org/10.1177/2041731420975569
work_keys_str_mv AT jinqiaoqiao extracellularvesiclesderivedfromhumandentalpulpstemcellspromoteosteogenesisofadiposederivedstemcellsviathemapkpathway
AT lipeilun extracellularvesiclesderivedfromhumandentalpulpstemcellspromoteosteogenesisofadiposederivedstemcellsviathemapkpathway
AT yuankeyong extracellularvesiclesderivedfromhumandentalpulpstemcellspromoteosteogenesisofadiposederivedstemcellsviathemapkpathway
AT zhaofen extracellularvesiclesderivedfromhumandentalpulpstemcellspromoteosteogenesisofadiposederivedstemcellsviathemapkpathway
AT zhuxiaohan extracellularvesiclesderivedfromhumandentalpulpstemcellspromoteosteogenesisofadiposederivedstemcellsviathemapkpathway
AT zhangpengfei extracellularvesiclesderivedfromhumandentalpulpstemcellspromoteosteogenesisofadiposederivedstemcellsviathemapkpathway
AT huangzhengwei extracellularvesiclesderivedfromhumandentalpulpstemcellspromoteosteogenesisofadiposederivedstemcellsviathemapkpathway