Researchers discover mechanism involved in dental inflammation

Researchers at the University of São Paulo in Brazil have discovered connections in the mechanisms involved in dental pulp inflammation and root apex damage. The findings may lead to medications that can prevent bone loss due to endodontic infection.

The team's results were published recently in the Journal of Endodontics. The researchers found that tumor necrosis factor-α receptor-1, TNFR1, is involved in the formation of reparative dentin after dental pulp capping. Pulp capping is a procedure in which bioactive material is placed over exposed pulp to encourage healing at the site of injury. TNFR1 becomes proinflammatory on binding to the cytokine TNF-α.

The team showed that in one analysis, the TNF-α-TNFR1 signaling pathway protected teeth and allowed for repair. However, in another case, it acted in an antagonistic manner, leading to an inflammatory process with bone loss. The difference between the two situations was due to the presence or absence of microorganisms, the team wrote.

When TNFR1 is ablated (genetically removed or deactivated), the inflammatory response is altered and the expression of key mineralization proteins (dentin sialoprotein and osteopontin) is inhibited thus leading to dental pulp necrosis and apical periodontitis. In this manner, the researchers demonstrated in vivo that this proinflammatory signaling pathway is important to cell differentiation and the synthesis of proteins that control the process of dental biomineralization, a crucial process for successful dental healing. 

In one study on reparative dentin formation, the researchers compared the dental pulp repair response of TNFR1-deficient mice with that of wild-type mice (C57BL/6 strain) as the control group. Pulp capping was performed with mineral trioxide aggregate. The researchers reported that genetic ablation of TNFR1 modified the inflammatory process and inhibited the expression of mineralization proteins. This led to dental pulp necrosis and the development of apical periodontitis. 

In another study on the role of the TNF-α-TNFR1 signaling pathway, the researchers induced apical periodontitis by inoculating oral microorganisms into the molar root canals of mice lacking TNFR1 and compared their response with that of the wild-type control group. They showed that lower recruitment of neutrophils in TNFR1-deficient mice resulted in a reduced apical periodontitis area and volume at 42 days. The number of osteoclasts (cells that mediate bone loss in pathological conditions) was also lower in TNFR1-deficient mice at 14 and 42 days.

The team said it is now investigating therapeutic approaches based on the results of these two studies.