Root Research: How Research and Advancing Knowledge of the Oral Environment are Impacting Endodontics

Endodontics is a constantly evolving field that relies heavily on emerging research and a deep understanding of the oral environment and the subsequent effects it has on oral health. As researchers learn more about the oral microbiome, genetics, and the oral cavity as a whole, endodontists become better equipped to effectively treat endodontic disease. 

Over the past several decades, an increasing focus on the investigation into causes of inflammation has changed the way clinicians approach endodontic treatment. Microenvironmental changes that affect the oral microbiota and genetic predispositions have been studied at length in an attempt to better understand why issues arise in endodontic cases—and how those issues can lead to case failure. While there are still many factors that have not been identified or are not yet fully understood, the advancing knowledge of the oral environment has made great leaps in recent years.

Genetics

In recent years, research into the human genome has greatly impacted endodontics. While much is known about the effects of microbial infections on oral health, less is understood about genetic factors in disease susceptibility. Studies have suggested that DNA may play a factor in a patient’s susceptibility to pulpal or periapical diseases. Separated from the etiologic factors, and understanding of these underlying molecular mechanisms could better target future therapeutic approaches for more personalized treatment strategies.¹ And clinicians are curious about the implications.

“A fascinating area of current study is the effect of the individual characteristics of the human genome and its effect on inflammation and endodontic healing,” says Richard Mounce, DDS, an endodontist practicing in Pacific City, Oregon. “It appears that with time we will be able to correlate the probabilities more clearly for healing with the patients DNA and other medical conditions.”

But it’s not only the patient’s DNA that can play a part. The DNA of the bacteria in the oral microbiome can also be a factor in infected root canals. A recent study used genomic DNA probes and checkerboard DNA-DNA hybridization to detect bacterial species that are difficult to identify, making them nearly impossible to treat. The ability to identify bacteria more effectively will lead to advances in treatment, as clinicians will be able to target the specific problematic pathogen.

“The microbiologic data of the present investigation indicated that molecular genetic methods can provide significant additional knowledge regarding the endodontic microbiota by detecting bacterial species that are difficult or impossible to culture,” the study’s authors concluded. “In addition, our findings support the current concept that endodontic infections are mixed infections of polymicrobial etiology.”²

Although genetics may affect the propensity for the need of endodontic treatment—and how the treatment itself is approached—endodontic treatment may also be affecting genetics. Researchers have been exploring the genotoxic potential of some of the compounds used in endodontic treatment. Genotoxicity, or the ability of a material to produce damage to the DNA molecule, is of particular concern in endodontic treatment as the dental materials used are designed to remain in the oral environment for long periods of time. In particular, endodontic compounds and cements and restorative materials pose concerns for researchers, as endodontic cements and epoxy resins can produce formaldehyde, a well-known carcinogen.^3,4 Other endodontic compounds, such as calcium hydroxide, resin-based sealers, phenolic compounds, chlorhexidine, and mineral trioxide aggregate, are also under the microscope.⁴

“Some of these compounds appear capable of exerting noxious activity on the genetic material,” one study states. “Therefore, this is an area that warrants investigation since the estimation of risk of these substances with respect to genotoxicity will be added to those used for regulatory purposes in improving oral health and preventing oral carcinogenesis.”⁵

Bacterial and viral impacts

While research on the part played by genetics continues, investigation into oral bacteria and viruses also march on. In light of the COVID-19 pandemic, researchers have also been exploring the effects of viruses in regards to pulpitis and the subsequent root-canal therapy it often necessitates. While the most common cause of pulpitis is bacterial infiltration of the dental pulp through an area of tooth decay, a recent study found that the SARS-CoV-2 virus can also similarly affect the dental pulp. 

“Master Regulator Analysis of the SARS-CoV-2/human interactome identified 75 relevant genes whose expression values are either up-regulated or down-regulated in both the human interactome and pulpitis,” the study’s authors wrote. “Our results suggest that the dental pulp is vulnerable to SARS-CoV2 infection and that SARS-CoV-2 infection of the dental pulp may contribute to worse outcomes of pulpitis.”⁶

As more is learned about the effects of inflammatory conditions caused by microorganisms and pathogens on pulp and periapical tissues, better defensive steps can be taken to boost preventative measures and immune responses. What causes a change in the balance between microorganisms and the oral microbiome that leads to inflammatory complications, infection, and periapical responses? How can we perform better microbial detection? A greater understanding of these issues is surely on the horizon, and the implications it will have for endodontics will be significant.

Gaps that still need to be filled

While knowledge of the oral environment has certainly improved, it bears repeating that there are still many of these questions left unanswered.

“There are many gaps in our knowledge of the oral environment and its effect on endodontics,” Dr Mounce says. “For example, we don't have a conclusive understanding of temporomandibular joint disorders (TMDs) and there is only modest agreement on its treatment.”

The correlation of TMD to endodontic diagnosis, coronal fractures, vertical root fracture, etc., and optimal long-term restorative outcomes and concepts is, Dr Mounce says, something that would be hugely beneficial to the endodontic field. He offers up the example of a well-treated molar tooth that continues to hurt while chewing after a crown is placed in the presence of TMB: “If occlusion has been optimized, why is this happening? We just don’t know yet.”  

While clinicians are still left with many pressing questions, Dr Mounce is certain that rapidly progressing research will soon change the field.

“All of this emerging research will advance endodontics,” Dr Mounce says. “Some of our time-honored beliefs about what makes treatment succeed or fail (excellent cleaning and shaping and obturation and coronal seal equals healing) may be slowly changing or at least modified.”

References

1. Fouad Ashraf F., Khan Asma A., Silva Renato M., Kang Mo K. Genetic and Epigenetic Characterization of Pulpal and Periapical Inflammation. Front. Physiol, 2020; 11 

2. Siqueira JF Jr, Rôças IN, Souto R, de Uzeda M, Colombo AP. Checkerboard DNA-DNA hybridization analysis of endodontic infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Jun;89(6):744-8.

3. Athanassiadis B, George G.A., Abbott P.V., Wash L. J. A review of the effects of formaldehyde release from endodontic materials. International Endodontic Journal, 2015;48, 829–838

4. Ribiero DA, Yujra VQ, Gomes de Moura CF, Handan BA, De Barros Viana M, Yamauchi LY, Castelo PM, Aguiar O. Genotoxicity induced by dental materials: A comprehensive review. Anticancer Research. 2017; 37 (8) 4017-4024.

5. Ribeiro DA. Do endodontic compounds induce genetic damage? A comprehensive review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 105(2):251-6.

6. Galicia, J.C., Guzzi, P.H., Giorgi, F.M. et al. Predicting the response of the dental pulp to SARS-CoV2 infection: a transcriptome-wide effect cross-analysis. Genes Immun. 2020; 21, 360–363