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Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis
Extensive macrophage inflammatory responses and osteoclast formation are predominant during inflammatory or infective osteolysis. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) have been shown to exert therapeutic effects on bone defects. However, cultured MSCs are typica...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
KeAi Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587346/ https://www.ncbi.nlm.nih.gov/pubmed/36311048 http://dx.doi.org/10.1016/j.bioactmat.2022.10.001 |
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author | Tian, Jun Chen, Weiyang Xiong, Yuhua Li, Qianer Kong, Siyi Li, Mengjie Pang, Chunfeng Qiu, Yu Xu, Zhezhen Gong, Qimei Wei, Xi |
author_facet | Tian, Jun Chen, Weiyang Xiong, Yuhua Li, Qianer Kong, Siyi Li, Mengjie Pang, Chunfeng Qiu, Yu Xu, Zhezhen Gong, Qimei Wei, Xi |
author_sort | Tian, Jun |
collection | PubMed |
description | Extensive macrophage inflammatory responses and osteoclast formation are predominant during inflammatory or infective osteolysis. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) have been shown to exert therapeutic effects on bone defects. However, cultured MSCs are typically exposed to normoxia (21% O(2)) in vitro, which differs largely from the oxygen concentration in vivo under hypoxic conditions. It is largely unknown whether sEV derived from dental pulp stem cells (DPSCs) cultured under hypoxic conditions (Hypo-sEV) exert better therapeutic effects on lipopolysaccharide (LPS)-induced inflammatory osteolysis than those cultured under normoxic conditions (Nor-sEV) by simultaneously inhibiting the macrophage inflammatory response and osteoclastogenesis. In this study, we show that hypoxia significantly induces the release of sEV from DPSCs. Moreover, Hypo-sEV exhibit significantly improved efficacy in promoting M2 macrophage polarization and suppressing osteoclast formation to alleviate LPS-induced inflammatory calvarial bone loss compared with Nor-sEV. Mechanistically, hypoxia preconditioning markedly alters the miRNA profiles of DPSC-sEV. MiR-210-3p is enriched in Hypo-sEV, and can simultaneously induce M2 macrophage generation and inhibit osteoclastogenesis by targeting NF-κB1 p105, which attenuates osteolysis. Our study suggests a promising potential for hypoxia-induced DPSC-sEV to treat inflammatory or infective osteolysis and identifies a novel role of miR-210-3p in concurrently hindering osteoclastogenesis and macrophage inflammatory response by inhibiting NF-kB1 expression. |
format | Online Article Text |
id | pubmed-9587346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | KeAi Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-95873462022-10-27 Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis Tian, Jun Chen, Weiyang Xiong, Yuhua Li, Qianer Kong, Siyi Li, Mengjie Pang, Chunfeng Qiu, Yu Xu, Zhezhen Gong, Qimei Wei, Xi Bioact Mater Article Extensive macrophage inflammatory responses and osteoclast formation are predominant during inflammatory or infective osteolysis. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) have been shown to exert therapeutic effects on bone defects. However, cultured MSCs are typically exposed to normoxia (21% O(2)) in vitro, which differs largely from the oxygen concentration in vivo under hypoxic conditions. It is largely unknown whether sEV derived from dental pulp stem cells (DPSCs) cultured under hypoxic conditions (Hypo-sEV) exert better therapeutic effects on lipopolysaccharide (LPS)-induced inflammatory osteolysis than those cultured under normoxic conditions (Nor-sEV) by simultaneously inhibiting the macrophage inflammatory response and osteoclastogenesis. In this study, we show that hypoxia significantly induces the release of sEV from DPSCs. Moreover, Hypo-sEV exhibit significantly improved efficacy in promoting M2 macrophage polarization and suppressing osteoclast formation to alleviate LPS-induced inflammatory calvarial bone loss compared with Nor-sEV. Mechanistically, hypoxia preconditioning markedly alters the miRNA profiles of DPSC-sEV. MiR-210-3p is enriched in Hypo-sEV, and can simultaneously induce M2 macrophage generation and inhibit osteoclastogenesis by targeting NF-κB1 p105, which attenuates osteolysis. Our study suggests a promising potential for hypoxia-induced DPSC-sEV to treat inflammatory or infective osteolysis and identifies a novel role of miR-210-3p in concurrently hindering osteoclastogenesis and macrophage inflammatory response by inhibiting NF-kB1 expression. KeAi Publishing 2022-10-19 /pmc/articles/PMC9587346/ /pubmed/36311048 http://dx.doi.org/10.1016/j.bioactmat.2022.10.001 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Tian, Jun Chen, Weiyang Xiong, Yuhua Li, Qianer Kong, Siyi Li, Mengjie Pang, Chunfeng Qiu, Yu Xu, Zhezhen Gong, Qimei Wei, Xi Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis |
title | Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis |
title_full | Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis |
title_fullStr | Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis |
title_full_unstemmed | Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis |
title_short | Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis |
title_sort | small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587346/ https://www.ncbi.nlm.nih.gov/pubmed/36311048 http://dx.doi.org/10.1016/j.bioactmat.2022.10.001 |
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