Chloroquine and 3-Methyladenine Attenuates Periodontal Inflammation and Bone Loss in Experimental Periodontitis

He, Shasha; Zhou, Qian; Luo, Bing; Chen, Bin; Li, Lingjun; Yan, Fuhua

doi:10.1007/s10753-019-01111-0

Cited by 36 publications

(21 citation statements)

References 37 publications

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“…These differences may be due to the different types of cell or bacterial strains and different MOIs or conditions of infection used by the researcher, and they also reveal that after highly virulent bacterial infection and caused cellular stress, the regulation of autophagy has become a more intricate process than before [ 36 ]. Recent research has reported that P. gingivalis infection can activate autophagy in cementoblasts [ 60 ], human umbilical vein endothelial cells [ 61 ] and periodontal ligament fibroblasts [ 62 ], and subsequently generate damaging effects through inflammatory pathways, 3-MA and CQ may attenuate the inflammatory injury by suppressing autophagy activity and Beclin1 expression [ 63 ]. These studies proved a positive association between the occurrence and development of P. gingivalis -induced autophagy and inflammatory injury, However, the P. gingivalis -induced autophagy pathway can also prevent inflammation by regulating inflammatory signalling [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Associations of Porphyromonas gingivalis Infection and Low Beclin1 Expression With Clinicopathological Parameters and Survival of Esophageal Squamous Cell Carcinoma Patients

Guo¹,

Liu²,

Yang³

et al. 2021

Pathol. Oncol. Res.

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Purpose: The present study focused on exploring the associations of Porphyromonas gingivalis (P. gingivalis) infection and low Beclin1 expression with clinicopathological parameters and survival of esophageal squamous cell carcinoma (ESCC) patients, so as to illustrate its clinical significance and prognostic value.Methods: Immunohistochemistry (IHC) was used to detect P. gingivalis infection status and Beclin1 expression in 370 ESCC patients. The chi-square test was adopted to illustrate the relationship between categorical variables, and Cohen’s kappa coefficient was used for correlation analysis. Kaplan-Meier survival curves with the log-rank test were used to analyse the correlation of P. gingivalis infection and low Beclin1 expression with survival time. The effects of P. gingivalis infection and Beclin1 downregulation on the proliferation, migration and antiapoptotic abilities of ESCC cells in vitro were detected by Cell Counting Kit-8, wound healing and flow cytometry assays. For P. gingivalis infection of ESCC cells, cell culture medium was replaced with antibiotic-free medium when the density of ESCC cells was 70–80%, cells were inoculated with P. gingivalis at a multiplicity of infection (MOI) of 10.Result:P. gingivalis infection was negatively correlated with Beclin1 expression in ESCC tissues, and P. gingivalis infection and low Beclin1 expression were associated with differentiation status, tumor invasion depth, lymph node metastasis, clinical stage and prognosis in ESCC patients. In vitro experiments confirmed that P. gingivalis infection and Beclin1 downregulation potentiate the proliferation, migration and antiapoptotic abilities of ESCC cells (KYSE150 and KYSE30). Our results provide evidence that P. gingivalis infection and low Beclin1 expression were associated with the development and progression of ESCC.Conclusion: Long-term smoking and alcohol consumption causes poor oral and esophageal microenvironments and ESCC patients with these features were more susceptible to P. gingivalis infection and persistent colonization, and exhibited lower Beclin1 expression, worse prognosis and more advanced clinicopathological features. Our findings indicate that effectively eliminating P. gingivalis colonization and restoring Beclin1 expression in ESCC patients may contribute to preventation and targeted treatment, and yield new insights into the aetiological research on ESCC.

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Section: Discussionmentioning

confidence: 99%

Associations of Porphyromonas gingivalis Infection and Low Beclin1 Expression With Clinicopathological Parameters and Survival of Esophageal Squamous Cell Carcinoma Patients

Guo¹,

Liu²,

Yang³

et al. 2021

Pathol. Oncol. Res.

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“…Recently, He et al showed that the number of TRAP‐positive multinucleated cells was lower in a group using autophagy inhibitors 3‐MA or chloroquine. Furthermore, 3‐MA downregulated LPS‐induced osteoclast formation in a periodontitis rat model 100 …”

Section: Autophagy and Alveolar Bone Homeostasismentioning

confidence: 96%

Autophagy and its significance in periodontal disease

Yang

Huang

2020

J of Periodontal Research

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Autophagy is an evolutionarily conserved process essential for cellular homeostasis and human health. As a lysosome‐dependent degradation pathway, autophagy acts as a modulator of the pathogenesis of diverse diseases. The relationship between autophagy and oral diseases has been explored in recent years, and there is increasing interest in the role of autophagy in periodontal disease. Periodontal disease is a prevalent chronic inflammatory disorder characterized by the destruction of periodontal tissues. It is initiated through pathogenic bacterial infection and interacts with the host immune defense, leading to inflammation and alveolar bone resorption. In this review, we outline the machinery of autophagy and present an overview of work on the significance of autophagy in regulating pathogen invasion, the immune response, inflammation, and alveolar bone homeostasis of periodontal disease. Existing data provide support for the importance of autophagy as a multi‐dimensional regulator in the pathogenesis of periodontal disease and demonstrate the importance of future research on the potential roles of autophagy in periodontal disease.

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“…Recent studies have found that autophagy-related proteins are important regulators of osteoclast differentiation and function 19 , 20 . Both autophagy inhibitors 3-Methyladenine and chloroquine can effectively down-regulate the expression of osteoclast-related genes and inhibit osteoclastogenesis and its function 21 , 22 . Silencing the autophagy-associated gene Beclin1 in osteoclast precursors inhibits osteoclast differentiation and maturation.…”

Section: Introductionmentioning

confidence: 99%

PERK controls bone homeostasis through the regulation of osteoclast differentiation and function

et al. 2020

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Osteoclasts are multinucleated giant cells with the ability to degrade bone tissue, and are closely related to abnormal bone metabolic diseases. Endoplasmic reticulum (ER) is an organelle responsible for protein modification, quality control, and transportation. The accumulation of unfolded or misfolded proteins in ER cavity induces ER stress. Double-stranded RNA-dependent protein kinase-like ER kinase (PERK) is an ER stress-sensing protein, which is ubiquitous in eukaryotic cells. Systemic PERK knockout mice show severe bone loss, suggesting that PERK is of great significance for maintaining the normal growth and development of bone tissue, but the role of PERK in osteoclastogenesis is still unclear. In this study, we found that PERK was significantly activated during RANKL-induced osteoclast differentiation; knockdown of PERK by siRNA and inhibition of PERK by GSK2606414, respectively, had significant negative regulatory effects on the formation and bone resorption of osteoclasts. PERK inhibitor GSK2606414 down-regulated the mRNA levels and protein expression of osteoclast differentiation marker genes, and inhibited RANKL-induced activation of Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways. Treatment with PERK inhibitor GSK2606414 in ovariectomized mouse model significantly suppressed bone loss and osteoclast formation. Thapsigargin activated ER stress to enhance autophagy, while GSK2606414 had a significant inhibitory effect on autophagy flux and autophagosome formation. Antioxidant N-acetylcysteine (NAC) could inhibit the expression of PERK phosphorylation, osteoclast-related proteins and autophagy-related proteins, but the use of PERK activator CCT020312 can reverse inhibition effect of NAC. Our findings demonstrate a key role for PERK in osteoclast differentiation and suggest its therapeutic potential.

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Chloroquine and 3-Methyladenine Attenuates Periodontal Inflammation and Bone Loss in Experimental Periodontitis

Cited by 36 publications

References 37 publications

Associations of Porphyromonas gingivalis Infection and Low Beclin1 Expression With Clinicopathological Parameters and Survival of Esophageal Squamous Cell Carcinoma Patients

Associations of Porphyromonas gingivalis Infection and Low Beclin1 Expression With Clinicopathological Parameters and Survival of Esophageal Squamous Cell Carcinoma Patients

Autophagy and its significance in periodontal disease

PERK controls bone homeostasis through the regulation of osteoclast differentiation and function

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