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      Methylenetetrahydrofolate reductase polymorphisms in dental caries-induced pulp inflammation and regeneration of dentine-pulp complex: Future perspectives

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          Abstract

          Dental caries (DC)-induced pulp infections usually undergo the common endodontic treatment, root canal therapy (RCT). Endodontically treated teeth are devitalized, become brittle and susceptible for re-infection which eventually results in dental loss. These complications arise because the devitalized pulp losses its ability for innate homeostasis, repair and regeneration. Therefore, restoring the vitality, structure and function of the inflamed pulp and compromised dentin have become the focal points in regenerative endodontics. There are very few evidences, so far, that connect methylenetetrahydrofolate reductase single nucleotide polymorphisms (MTHFR-SNPs) and dental disorders. However, the primary consequences of MTHFR-SNPs, in terms of excessive homocysteine and folate deficiency, are well-known contributors to dental diseases. This article identifies the possible mechanisms by which MTHFR-SNP-carriers are susceptible for DC-induced pulp inflammation (PI); and discusses a cell-homing based strategy for in vivo transplantation in an orthotopic model to regenerate the functional dentine-pulp complex which includes dentinogenesis, neurogenesis and vasculogenesis, in the SNP-carriers.

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          Most cited references55

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          Global, Regional, and National Levels and Trends in Burden of Oral Conditions from 1990 to 2017: A Systematic Analysis for the Global Burden of Disease 2017 Study

          Government and nongovernmental organizations need national and global estimates on the descriptive epidemiology of common oral conditions for policy planning and evaluation. The aim of this component of the Global Burden of Disease study was to produce estimates on prevalence, incidence, and years lived with disability for oral conditions from 1990 to 2017 by sex, age, and countries. In addition, this study reports the global socioeconomic pattern in burden of oral conditions by the standard World Bank classification of economies as well as the Global Burden of Disease Socio-demographic Index. The findings show that oral conditions remain a substantial population health challenge. Globally, there were 3.5 billion cases (95% uncertainty interval [95% UI], 3.2 to 3.7 billion) of oral conditions, of which 2.3 billion (95% UI, 2.1 to 2.5 billion) had untreated caries in permanent teeth, 796 million (95% UI, 671 to 930 million) had severe periodontitis, 532 million (95% UI, 443 to 622 million) had untreated caries in deciduous teeth, 267 million (95% UI, 235 to 300 million) had total tooth loss, and 139 million (95% UI, 133 to 146 million) had other oral conditions in 2017. Several patterns emerged when the World Bank’s classification of economies and the Socio-demographic Index were used as indicators of economic development. In general, more economically developed countries have the lowest burden of untreated dental caries and severe periodontitis and the highest burden of total tooth loss. The findings offer an opportunity for policy makers to identify successful oral health strategies and strengthen them; introduce and monitor different approaches where oral diseases are increasing; plan integration of oral health in the agenda for prevention of noncommunicable diseases; and estimate the cost of providing universal coverage for dental care.
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            Dental Pulp Defence and Repair Mechanisms in Dental Caries

            Dental caries is a chronic infectious disease resulting from the penetration of oral bacteria into the enamel and dentin. Microorganisms subsequently trigger inflammatory responses in the dental pulp. These events can lead to pulp healing if the infection is not too severe following the removal of diseased enamel and dentin tissues and clinical restoration of the tooth. However, chronic inflammation often persists in the pulp despite treatment, inducing permanent loss of normal tissue and reducing innate repair capacities. For complete tooth healing the formation of a reactionary/reparative dentin barrier to distance and protect the pulp from infectious agents and restorative materials is required. Clinical and in vitro experimental data clearly indicate that dentin barrier formation only occurs when pulp inflammation and infection are minimised, thus enabling reestablishment of tissue homeostasis and health. Therefore, promoting the resolution of pulp inflammation may provide a valuable therapeutic opportunity to ensure the sustainability of dental treatments. This paper focusses on key cellular and molecular mechanisms involved in pulp responses to bacteria and in the pulpal transition between caries-induced inflammation and dentinogenic-based repair. We report, using selected examples, different strategies potentially used by odontoblasts and specialized immune cells to combat dentin-invading bacteria in vivo.
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              Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition.

              Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional and/or genetic disruptions in homocysteine metabolism. The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. This variant, with mild enzymatic deficiency, is associated with an increased risk for neural tube defects and pregnancy complications and with a decreased risk for colon cancer and leukemia. Although many studies have reported that this variant is also a risk factor for vascular disease, this area of investigation is still controversial. Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications. To investigate the in vivo pathogenetic mechanisms of MTHFR deficiency, we generated mice with a knockout of MTHFR: Plasma total homocysteine levels in heterozygous and homozygous knockout mice are 1.6- and 10-fold higher than those in wild-type littermates, respectively. Both heterozygous and homozygous knockouts have either significantly decreased S-adenosylmethionine levels or significantly increased S-adenosylhomocysteine levels, or both, with global DNA hypomethylation. The heterozygous knockout mice appear normal, whereas the homozygotes are smaller and show developmental retardation with cerebellar pathology. Abnormal lipid deposition in the proximal portion of the aorta was observed in older heterozygotes and homozygotes, alluding to an atherogenic effect of hyperhomocysteinemia in these mice.
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                Author and article information

                Contributors
                Journal
                Saudi Dent J
                Saudi Dent J
                The Saudi Dental Journal
                Elsevier
                1013-9052
                1658-3558
                30 August 2023
                December 2023
                30 August 2023
                : 35
                : 8
                : 1029-1038
                Affiliations
                [a ]Department of Cardiology, SRM Medical College Hospital and Research Center, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India
                [b ]Department of Zoology, College of Science, King Saud University, P.O.Box 2455, 11451 Riyadh, Saudi Arabia
                [c ]Department of Food Science & Biotechnology, Sejong University, Seoul 05006, Korea
                [d ]Department of Medical Research, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India
                Author notes
                [* ]Corresponding author. kanchana39@ 123456gmail.com
                Article
                S1013-9052(23)00158-X
                10.1016/j.sdentj.2023.08.008
                10759554
                f2aa3da9-34b2-4b42-a301-1b769950b4fe
                © 2023 King Saud University

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 29 December 2022
                : 3 August 2023
                : 17 August 2023
                Categories
                Original Article

                dental pi,methylenetetrahydrofolate reductase,single nucleotide polymorphism,cell-homing,orthotopic model,regenerative endodontics

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