Pulpitis, defined as the inflammation of the dental pulp, is a common disease that significantly impact the health of patients. Symptoms include toothache, discomfort during intake of hot or cold foods and beverages, and in severe cases, abscesses and general sepsis [33]. Clinicians face challenges in accurately determining the degree of dental pulp inflammation due to the lack of effective diagnostic methods, which adversely affects the outcomes of vital pulp therapy [34]. Glycolysis is one of the most important pathways of cellular energy metabolism, connected with several inflammatory diseases [35]. However, the present literature lacks a definite connection between glycolysis and pulpitis. The purpose of this research is to establish the relationship between alterations in glycolytic gene expression and pulpitis, with a view to enhancing disease diagnosis and management. Identifying key regulatory genes could reveal new biomarkers and therapeutic targets, thereby enhancing the diagnostic and prognostic accuracy of pulpitis. This, in turn, may help in the preservation of teeth and support oral and maxillofacial health.
Analysis of GEO datasets GSE77459 and GSE92681 showed that the expression levels of GRDEGs like PPBP and BIK were up-regulated in pulpitis, and the expressions of PRKAA2, GLCE, and VLDLR were downregulated, suggesting the involvement of energy metabolism in the development of pulpitis. Enrichment analysis identified that these GRDEGs are predominantly clustered with biological processes, cellular structures, and molecular activities related to energy production, consistent with the high energy demands required for sustaining inflammatory responses [36]. Notably, several GRDEGs located on chromosome 11 may play pivotal roles in modulating the glycolytic pathway during pulpitis development.
The recognition of hub genes, including HIF1A, LDHA, HK2, STAT3, TALDO1, PPARG, ALDOC, and PFKP, emphasizes their pivotal position within the PPI network and underscores their potential influence on disease progression. For instance, HIF1A is well-known to regulate cellular reactions to low oxygen tension and has relation to several inflammatory disorders due to its ability in controlling anaerobic respiration [37]. Also, LDHA and HK2 are glycolytic enzymes that increase in activity in inflamed tissue [38].
In addition, analysis of immune cell infiltration between the pulpitis and control groups revealed differences in the levels of 28 different immune cell types, including macrophages, dendritic cells, T lymphocytes, and B lymphocytes, which are involved in the processes of inflammation and tissue repair. For example, macrophages display various roles ranging from aggressive (M1) to the reparative (M2), which can affect the course of pulpitis [39]. Also, dendritic cells are crucial for antigen presentation and initiating specific immune responses, potentially influencing the chronicity of inflammatory conditions such as pulpitis [40]. Moreover, T lymphocyte subsets including Th1, Th2, Th17, and Treg are seen in pulpitis, indicating the intricate nature of the adaptive immune response. Th17 cells are linked with inflammation through IL-17 secretion, while Tregs suppress the immune responses to maintain tissue health [41]. Stewardship of these counterpoised influences may significantly affect the course of the disease.
The correlation between immunological cell types and hub genes discussed in this study gives some clues to possible molecular targets for future treatments. For instance, HIF1A, which is a transcription factor for hypoxia and inflammation, correlates with immune cell infiltration, indicating that dental pulp cells acclimatize to hypoxic conditions in an inflamed environment [42]. Also, the activation of STAT3 is associated with both pro-inflammatory mechanisms and anti-inflammatory actions [43], suggesting the complex role in the development of pulpitis. This study, through bioinformatics analysis, has identified multiple interactions of immune cells in pulpitis, paving the way for identifying specific diagnostic markers and treatment strategies.
However, there are some limitations that should be taken into consideration regarding the present study and the findings made on differential gene expression associated with pulpitis and their possible functions and roles in biological processes and molecular pathways. Firstly, our findings were not validated in wet-laboratory experiments. Secondly, the sample size was relatively low, which might have repercussions concerning the generalizability of the results. Finally, despite efforts to correct batch effects using computational methods, the combination of multiple datasets can introduce variability which may influence the robustness of our conclusions.