Dysregulated Phosphate Metabolism, Periodontal Disease, and Cancer: Possible Global Health Implications

Brown, Ronald B.

doi:10.3390/dj7010018

Cited by 7 publications

(9 citation statements)

References 70 publications

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“…Some studies show similar data for patients with periodontitis and patients without periodontal involvement [47,48], or minimal differences between the levels found in periodontal healthy sites and those with periodontitis [49,50]. Other studies point out considerable increase of crevicular TNF-α in periodontitis [51][52][53], supporting the fact that TNF-α concentration variations can be used to predict the progression of periodontal condition.…”

Section: Discussionmentioning

confidence: 87%

TNF-α, IL-1β, MMP-8 Crevicular Profile in Patients with Chronic Kidney Disease and Periodontitis

et al. 2022

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Increasing evidence sustains the potential of periodontitis as a risk factor for chronic kidney disease (CKD). Our study aimed to analyze several periodontal specific inflammatory biomarkers within the gingival crevicular fluid (GCF) of patients with CKD, compared to patients with normal kidney function, providing an inflammatory profile of the dialysis patient. The study comprised 79 patients divided into: group 1 (59 subjects with periodontitis and CKD) and group 2 (20 patients with periodontitis, without other systemic conditions). Clinical diagnosis was performed via dental and periodontal examination. GCF samples were collected from each patient, and the levels of TNF-α, IL-1β and MMP-8 were determined by using ELISA assay. In group 1, the average values were: 22.85 ± 5.87 pg/mL for TNF-α, 33.00 ± 39.68 pg/mL for IL-1β and 18.80 ± 27.75 ng/mL for MMP-8. In group 2, the mean values were: 2.10 ± 1.34 pg/mL for TNF-α, 0.71 ± 2.42 pg/mL for IL-1β and 5.35 ± 0.37 ng/mL for MMP-8. Statistical analysis revealed significant differences between groups as referring to all three biomarkers and, TNF-α and MMP-8, in certain stages of periodontitis. The level of TNF-α, IL-1β and MMP-8 points out the increased inflammatory status of the dialysis patient with PD, supporting the mutual connection of the two pathologies.

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Section: Discussionmentioning

confidence: 87%

TNF-α, IL-1β, MMP-8 Crevicular Profile in Patients with Chronic Kidney Disease and Periodontitis

et al. 2022

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“…When it comes to CKD-MBD, hyperphosphatemia increases phosphate levels in saliva, which is associated with a higher risk of inflammation of the periodontium. Furthermore, higher levels of phosphorus itself are linked to systemic inflammation [71]. This will enhance the association of periodontal disease and CKD.…”

Section: Periodontal Disease and Chronic Kidney Diseasementioning

confidence: 99%

Pathological Characteristics of Periodontal Disease in Patients with Chronic Kidney Disease and Kidney Transplantation

Kitamura

Mochizuki

Miyata

et al. 2019

IJMS

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Chronic kidney disease (CKD) is recognized as an irreversible reduction of functional nephrons and leads to an increased risk of various pathological conditions, including cardiovascular disease and neurological disorders, such as coronary artery calcification, hypertension, and stroke. In addition, CKD patients have impaired immunity against bacteria and viruses. Conversely, kidney transplantation (KT) is performed for patients with end-stage renal disease as a renal replacement therapy. Although kidney function is almost normalized by KT, immunosuppressive therapy is essential to maintain kidney allograft function and to prevent rejection. However, these patients are more susceptible to infection due to the immunosuppressive therapy required to maintain kidney allograft function. Thus, both CKD and KT present disadvantages in terms of suppression of immune function. Periodontal disease is defined as a chronic infection and inflammation of oral and periodontal tissues. Periodontal disease is characterized by the destruction of connective tissues of the periodontium and alveolar bone, which may lead to not only local symptoms but also systemic diseases, such as cardiovascular diseases, diabetes, liver disease, chronic obstructive pulmonary disease, and several types of cancer. In addition, the prevalence and severity of periodontal disease are significantly associated with mortality. Many researchers pay special attention to the pathological roles and clinical impact of periodontal disease in patients with CKD or KT. In this review, we provide information regarding important modulators of periodontal disease to better understand the relationship between periodontal disease and CKD and/or KT. Furthermore; we evaluate the impact of periodontal disease on various pathological conditions in patients with CKD and KT. Moreover, pathogens of periodontal disease common to CKD and KT are also discussed. Finally, we examine the importance of periodontal care in these patients. Thus, this review provides a comprehensive overview of the pathological roles and clinical significance of periodontal disease in patients with CKD and KT.

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“…135 Klotho as an Obligatory Co-receptor High concentrations of phosphate in the body are found in bone, teeth, and dental enamel as calcium phosphate crystals. 136,137 Klotho regulates phosphorus and calcium homeostasis 5,6,18,23,138 and functions as an obligatory co-receptor that binds and activates its related endocrine fibroblast growth factor (FGF) receptors (FGFRs) to potentiate its biological activities. 5,6,23,102,[139][140][141][142][143][144][145][146] FGFs are exemplary pleiotropic hormones that play numerous roles in cellular and metabolic homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…5,6,23,102,[139][140][141][142][143][144][145][146] FGFs are exemplary pleiotropic hormones that play numerous roles in cellular and metabolic homeostasis. 5,6,137,141,[144][145][146][147][148] In particular, FGF23 is a bone-derived hormone that in conjunction with Klotho acts on the kidney to increase phosphate excretion and suppress biosynthesis of vitamin D. 5,6,14,23,102,136,138,145,148,149 Vitamin D regulates epigenetic mechanisms that maintain the transcription of its target genes in regulatory networks, including the expression of Klotho and nuclear factor-erythroid-2related factor 2 (Nrf2) to carry out many of its homoeostatic functions. 17,97,[150][151][152][153] Vitamin D is a modulator of the immune system, 154,155 hence its mention here, and accumulating evidence suggests vitamin D deficiency is a risk factor for dysregulated Klotho-associated neurodegenerative diseases, the most noteworthy being MS. 9,27,52,97,…”

Section: Introductionmentioning

confidence: 99%

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Moos

Faller

Glavas

et al. 2020

BioResearch Open Access

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In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.

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Dysregulated Phosphate Metabolism, Periodontal Disease, and Cancer: Possible Global Health Implications

Cited by 7 publications

References 70 publications

TNF-α, IL-1β, MMP-8 Crevicular Profile in Patients with Chronic Kidney Disease and Periodontitis

TNF-α, IL-1β, MMP-8 Crevicular Profile in Patients with Chronic Kidney Disease and Periodontitis

Pathological Characteristics of Periodontal Disease in Patients with Chronic Kidney Disease and Kidney Transplantation

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

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