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Local anesthetics induce autophagy in young permanent tooth pulp cells

View Article: PubMed Central - PubMed

ABSTRACT

Pulp cells are essential for tooth development, and dentin repair and regeneration. In addition these cells have been identified as an important stem cell source. Local anesthetics are widely used in dental clinics, as well as the other clinical disciplines and have been suggested to interfere with human permanent tooth development and induce tooth agenesis through unknown mechanisms. Using pig model and human young permanent tooth pulp cells, our research has identified that the local anesthetics commonly used in clinics can affect cell proliferation. Molecular pathway profiling suggested that LC3II is one of the earliest molecules induced by the agents and p62 is the only common downstream target identified for all the drugs tested. The effect of the drugs could be partially recovered by V-ATPase inhibitor only if early intervention is performed. Our results provide novel evidence that local anesthetics could affect tooth cell growth that potentially can have impacts on tooth development.

No MeSH data available.


Local anesthetics affect tooth pulp cellular energetics. Key parameters of mitochondrial function including basal respiration, phosphorylation, proton leak and maximum respiration were tested by directly measuring the oxygen consumption rate (OCR) of cells treated with the five anesthetics with 0.5 and 2 mM concentrations for 2 h (a) and 16 h (b) (8, 16 h results can be found in Supplementary Figure 5). Note that at 16 h basal respiration, phosphorylation and maximum respiration were all reduced in the 2 mM UBI-F, Sept, Scan and Lido treated cells. Lido, Lidocaine; UBI, Ubistesin; UBI-F, Ubistesin forte; Scan, Scandonest; Sept, Septanest. Number abbreviations after individual drug abbreviation: 0.5: 0.5 mM; 2: 2 mM. *P<0.05; **P<0.01.
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fig5: Local anesthetics affect tooth pulp cellular energetics. Key parameters of mitochondrial function including basal respiration, phosphorylation, proton leak and maximum respiration were tested by directly measuring the oxygen consumption rate (OCR) of cells treated with the five anesthetics with 0.5 and 2 mM concentrations for 2 h (a) and 16 h (b) (8, 16 h results can be found in Supplementary Figure 5). Note that at 16 h basal respiration, phosphorylation and maximum respiration were all reduced in the 2 mM UBI-F, Sept, Scan and Lido treated cells. Lido, Lidocaine; UBI, Ubistesin; UBI-F, Ubistesin forte; Scan, Scandonest; Sept, Septanest. Number abbreviations after individual drug abbreviation: 0.5: 0.5 mM; 2: 2 mM. *P<0.05; **P<0.01.

Mentions: Local anesthetics have been known to be able to induce cellular stress and autophagy that has been linked with mitochondrial dysfunctions. We therefore measured dynamic cellular energetics using the Seahorse XF reader in cells received local anesthetics challenge. The results showed unexpectedly that at time points 2, 4 and 8 h, all the parameters tested including basal respiration, phosphorylation, proton leak and maximum respiration were induced in the agents treated cells for most of the cases (Figures 5a and b and Supplementary Figures 5A and B) with the exception of the 16-h time point at 2 mM but not 0.5 mM concentration four out of five drugs tested reduced basal respiration, phosphorylation and maximum respiration but not proton leak (Figure 5a and b and Supplementary Figures 5A and B). These results indicate that mitochondrial functions were disturbed only at high concentration (2 mM) after 16 h.


Local anesthetics induce autophagy in young permanent tooth pulp cells
Local anesthetics affect tooth pulp cellular energetics. Key parameters of mitochondrial function including basal respiration, phosphorylation, proton leak and maximum respiration were tested by directly measuring the oxygen consumption rate (OCR) of cells treated with the five anesthetics with 0.5 and 2 mM concentrations for 2 h (a) and 16 h (b) (8, 16 h results can be found in Supplementary Figure 5). Note that at 16 h basal respiration, phosphorylation and maximum respiration were all reduced in the 2 mM UBI-F, Sept, Scan and Lido treated cells. Lido, Lidocaine; UBI, Ubistesin; UBI-F, Ubistesin forte; Scan, Scandonest; Sept, Septanest. Number abbreviations after individual drug abbreviation: 0.5: 0.5 mM; 2: 2 mM. *P<0.05; **P<0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979463&req=5

fig5: Local anesthetics affect tooth pulp cellular energetics. Key parameters of mitochondrial function including basal respiration, phosphorylation, proton leak and maximum respiration were tested by directly measuring the oxygen consumption rate (OCR) of cells treated with the five anesthetics with 0.5 and 2 mM concentrations for 2 h (a) and 16 h (b) (8, 16 h results can be found in Supplementary Figure 5). Note that at 16 h basal respiration, phosphorylation and maximum respiration were all reduced in the 2 mM UBI-F, Sept, Scan and Lido treated cells. Lido, Lidocaine; UBI, Ubistesin; UBI-F, Ubistesin forte; Scan, Scandonest; Sept, Septanest. Number abbreviations after individual drug abbreviation: 0.5: 0.5 mM; 2: 2 mM. *P<0.05; **P<0.01.
Mentions: Local anesthetics have been known to be able to induce cellular stress and autophagy that has been linked with mitochondrial dysfunctions. We therefore measured dynamic cellular energetics using the Seahorse XF reader in cells received local anesthetics challenge. The results showed unexpectedly that at time points 2, 4 and 8 h, all the parameters tested including basal respiration, phosphorylation, proton leak and maximum respiration were induced in the agents treated cells for most of the cases (Figures 5a and b and Supplementary Figures 5A and B) with the exception of the 16-h time point at 2 mM but not 0.5 mM concentration four out of five drugs tested reduced basal respiration, phosphorylation and maximum respiration but not proton leak (Figure 5a and b and Supplementary Figures 5A and B). These results indicate that mitochondrial functions were disturbed only at high concentration (2 mM) after 16 h.

View Article: PubMed Central - PubMed

ABSTRACT

Pulp cells are essential for tooth development, and dentin repair and regeneration. In addition these cells have been identified as an important stem cell source. Local anesthetics are widely used in dental clinics, as well as the other clinical disciplines and have been suggested to interfere with human permanent tooth development and induce tooth agenesis through unknown mechanisms. Using pig model and human young permanent tooth pulp cells, our research has identified that the local anesthetics commonly used in clinics can affect cell proliferation. Molecular pathway profiling suggested that LC3II is one of the earliest molecules induced by the agents and p62 is the only common downstream target identified for all the drugs tested. The effect of the drugs could be partially recovered by V-ATPase inhibitor only if early intervention is performed. Our results provide novel evidence that local anesthetics could affect tooth cell growth that potentially can have impacts on tooth development.

No MeSH data available.