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Updated: Aug 23, 2025
Author Spotlight: Advancing Tissue Regeneration and Disease Modeling with Dental Pulp Stem Cells
Published on: May 5, 2023
Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory
Jun Tian1,2, Weiyang Chen1,2, Yuhua Xiong1,2
1Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, PR China.
Abstract:
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% O2) 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.
Insights
Hypoxia-conditioned dental pulp stem cell-derived small extracellular vesicles (Hypo-sEV) show enhanced therapeutic effects for inflammatory osteolysis. Hypo-sEV promote M2 macrophage polarization and inhibit osteoclast formation more effectively than normoxia-derived sEV.
Area of Science:
- Stem cell biology
- Extracellular vesicles
- Immunomodulation
- Bone biology
Background:
- Inflammatory osteolysis involves macrophage activation and osteoclast formation.
- Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) show therapeutic potential for bone defects.
- In vitro culture conditions (normoxia) differ from in vivo (hypoxia), potentially affecting MSC-sEV efficacy.
Purpose of the Study:
- To investigate if small extracellular vesicles (sEV) from dental pulp stem cells (DPSCs) cultured under hypoxia (Hypo-sEV) offer superior therapeutic effects on lipopolysaccharide (LPS)-induced osteolysis compared to those cultured under normoxia (Nor-sEV).
- To determine if Hypo-sEV can simultaneously inhibit macrophage inflammatory responses and osteoclastogenesis.
Main Methods:
- DPSCs were cultured under normoxic and hypoxic conditions to isolate sEV.
- The efficacy of Hypo-sEV and Nor-sEV in promoting M2 macrophage polarization and suppressing osteoclast formation was evaluated in vitro and in vivo.
- MiRNA profiles of Hypo-sEV were analyzed, and the role of enriched miRNAs in regulating macrophage polarization and osteoclastogenesis was investigated.
Main Results:
- Hypoxia significantly increased sEV release from DPSCs.
- Hypo-sEV demonstrated superior efficacy in promoting M2 macrophage polarization and suppressing osteoclast formation, leading to reduced LPS-induced calvarial bone loss compared to Nor-sEV.
- MiR-210-3p was enriched in Hypo-sEV and was found to target NF-κB1 p105, thereby inhibiting both osteoclastogenesis and macrophage inflammatory responses.
Conclusions:
- Hypoxia preconditioning enhances the therapeutic potential of DPSC-sEV for treating inflammatory osteolysis.
- Hypoxia-induced DPSC-sEV offer a promising cell-free therapeutic strategy for inflammatory or infective osteolysis.
- MiR-210-3p plays a crucial role in the dual action of Hypo-sEV by inhibiting both osteoclastogenesis and macrophage inflammation via NF-kB1 pathway.
