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. 2022 Jan 15;14(1):582-593.
eCollection 2022.

Pyrroloquinoline quinone inhibits ligature-induced alveolar bone loss through regulation of redox balance and cell senescence

Genxiong Tang  1 , Haoran Ma  1 , Shuying Liu  1 , Jun Wu  2 , Aixiu Gong  1
Affiliations

Pyrroloquinoline quinone inhibits ligature-induced alveolar bone loss through regulation of redox balance and cell senescence

Genxiong Tang et al. Am J Transl Res. .

Abstract

It has been demonstrated that oxidative stress is related to periodontitis, and that pyrroloquinoline quinine (PQQ) acts as a powerful antioxidant. This study aimed to explore the effect of PQQ on ligature-induced alveolar bone loss in experimental periodontitis (EP) mice with/without PQQ in the diet. EP mice received a diet supplemented with PQQ for 2 weeks and were compared with sham (control) mice as well as untreated EP mice. Additionally, human periodontal ligament cells (hPDLCs) were treated with PQQ in the presence or absence of lipopolysaccharide (LPS). We found that the bone volume fraction, alkaline phosphatase activity, and the number of antioxidant cells were significantly decreased in EP mice compared with the sham mice, whereas PQQ administration rescued the above effects. In contrast, alveolar bone loss, osteoclast number, cell senescence-associated cells, and cytokines' expression were significantly increased in EP mice compared with the sham mice but were significantly decreased with PQQ supplementation in periodontal tissues. Furthermore, we found that antioxidant enzymes and Bmi-1 protein expression levels were downregulated, whereas the protein expression levels of cell senescence-related proteins including γ-H2AX, IL-6, IL-1β, p16, and p21 were significantly up-regulated in LPS-induced hPDLCs compared with the control cells. However, PQQ administration partially prevented these changes. These findings suggest that PQQ may alleviate periodontal damage through regulation of the redox balance and cell senescence.

Keywords: Pyrroloquinoline quinone; alveolar bone resorption; inflammation; oxidative stress; periodontitis.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
The effect of PQQ on alveolar bone destruction in EP mice. A. Representative Micro-CT scans and 3D reconstructed sections of mouse maxilla. B. Two-dimensional (2D) sagittal plane of micro-CT scanned maxillary sections. C. Two-dimensional (2D) transverse plane of micro-CT scanned maxillary second molar (M2). D. The alveolar bone volume fraction (bone volume/total volume, BV/TV) was determined by micro-CT images of 3D reconstructed sections of M2 root furcation. The vertical data point is presented as means ± SEM, and the data were the means of ten specimens, and the differences between the groups were statistically analyzed using a one-way ANOVA followed by Bonferroni’s test. ***P<0.001, vs shame group; ###P<0.001, vs PQQ-untreated ligated mice.
Figure 2
Figure 2
The effect of PQQ on alveolar bone loss (ABL) in EP mice. A, B. Representative photomicrographs of paraffin sections of maxilla of each group histochemically stained for HE and total collagen. C. ABL was determined by HE image analysis. D. The percentage of total collagen positive area was determined by image analysis. Data are presented as means ± SEM, and each data point was the means of ten specimens, and the differences between the groups were statistically analyzed using a one-way ANOVA followed by Bonferroni’s test. ***P<0.001, vs shame group; ###P<0.001, vs PQQ-untreated ligated mice. A and B. Magnification, 50×.
Figure 3
Figure 3
The effect of PQQ on osteoblastic and osteoclastic alveolar bone formation in EP mice. A. Representative photomicrographs of paraffin sections of maxilla of each group histochemically stained for ALP. B. Representative photomicrographs of paraffin sections of maxilla of each group histochemically stained for TRAP. C. The percentage of ALP positive area was determined by image analysis. D. The number of TRAP-positive osteoclasts (N.Oc) per mm bone perimeter (B.Pm) was measured in the alveolar bone. Data are presented as means ± SEM, and each data point was the means of ten specimens. Data are presented as means ± SEM, and each data point was the means of ten specimens, and the differences between the groups were statistically analyzed using a one-way ANOVA followed by Bonferroni’s test. ***P<0.001, vs shame group; #P<0.05, ##P<0.01, vs PQQ-untreated ligated mice. A and B. Magnification, 400×.
Figure 4
Figure 4
The effect of PQQ on senescence-related inflammatory cells and cytokines in the gingiva in EP mice. A. Representative micrographs of paraffin sections of maxillae immunohistochemically stained for CD3. B. Representative micrographs of paraffin sections of maxillae immunohistochemically stained for NF-кB p65. C. The percentages of CD3 positive cells. D. The percentages of NF-кB p65 positive cells. E-H. Real-time RT-PCR was performed on the extracts of gingiva for gene expression of MMP-3, MMP-8, IL-1β and TNF-α. Messenger RNA expression, assessed by real-time RT-PCR analysis, is calculated as a ratio to that of β-actin mRNA level. Each value is presented as means ± SEM, and the data were the means of ten specimens, and the differences between the groups were statistically analyzed using a one-way ANOVA followed by Bonferroni’s test. ***P<0.001, vs shame group; ##P<0.01, ###P<0.001, vs PQQ-untreated ligated mice. A and B. Magnification, 400×.
Figure 5
Figure 5
The effect of PQQ on antioxidant enzyme expression and senescence-related inflammatory cells in the alveolar bone area in EP mice. A-C. Representative micrographs of paraffin sections of maxillae immunohistochemically stained for SOD2, IL-1β and IL-6. D-F. The percentages of SOD2, IL-1β and IL-6 positive cells. Each value is presented as means ± SEM, and the data were the means of ten specimens, and the differences between the groups were statistically analyzed using a one-way ANOVA followed by Bonferroni’s test. ***P<0.001, vs shame group; #P<0.05, ###P<0.001, vs PQQ-untreated ligated mice. A-C. Magnification, 400×.
Figure 6
Figure 6
Effects of PQQ on redox balance and cell senescence-related markers in LPS-induced hPDLCs. A. Western blots of cell extracts for the expression of SOD1, SOD2, Bmi-1, γ-H2AX, IL-6, IL-1β, p21, p16. ß-actin was used as loading control for Western blots. B-I. Quantification of protein relative expression levels of SOD1, SOD2, Bmi-1, γ-H2AX, IL-1β, IL-6, p21 and p16 assessed by densitometric analysis. Values are means ± SEM of 6 determinations per group, and the differences between the groups were statistically analyzed using a one-way ANOVA followed by Bonferroni’s test. *P<0.05, **P<0.01, vs vehicle-induced group; #P<0.05, vs PQQ-untreated LPS-induced group.
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