This work describes the current state of research on the potential relationship between protein content in human saliva and dental caries, which remains among the most common oral diseases and causes irreversible damage in the oral cavity. An understanding the whole saliva proteome in the oral cavity could serve as a prerequisite to obtaining insight into the etiology of tooth decay at early stages. To date, however, there is no comprehensive evidence showing that salivary proteins could serve as potential indicators for the early diagnosis of the risk factors causing dental caries. Therefore, proteomics indicates the promising direction of future investigations of such factors, including diagnosis and thus prevention in dental therapy.

The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the literature by searching PubMed, Web of Science, and ProQuest databases for genes, proteins, and microRNAs associated with MRONJ from the earliest records through April 2023. Conference abstracts, letters, review articles, non-human studies, and non-English publications were excluded. Twelve studies meeting the inclusion criteria involving exposure of human oral mucosa, blood, serum, saliva, or adjacent bone or periodontium to anti-resorptive or anti-angiogenic agents were analyzed. The Cochrane Collaboration risk assessment tool was used to assess the quality of the studies. A total of 824 differentially expressed genes/proteins (DEGs) and 22 microRNAs were extracted for further bioinformatic analysis using Cytoscape, STRING, BiNGO, cytoHubba, MCODE, and ReactomeFI software packages and web-based platforms: DIANA mirPath, OmicsNet, and miRNet tools. The analysis yielded an interactome consisting of 17 hub genes and hsa-mir-16-1, hsa-mir-21, hsa-mir-23a, hsa-mir-145, hsa-mir-186, hsa-mir-221, and hsa-mir-424. A dominance of cytokine pathways was observed in both the cluster of hub DEGs and the interactome of hub genes with dysregulated miRNAs. In conclusion, a panel of genes, miRNAs, and related pathways were found, which is a step toward understanding the complexity of the disease.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies, yet its molecular mechanisms remain poorly defined. The present study employed an analysis of microarray data (GSE7116) from peripheral blood mononuclear cells of patients with multiple myeloma, myeloma patients with MRONJ, and healthy controls. Differentially expressed genes were identified using the limma package, followed by functional enrichment analysis, weighted gene co-expression network analysis, and LASSO regression and CytoHubba network ranking. The predictive performance was validated by means of nested cross-validation, Firth logistic regression, and safe stratified 0.632+ bootstrap ridge regression. The profiling revealed distinct gene expression patterns between the groups: the upregulation of ribosomal and translational pathways, as well as the suppression of neutrophil degranulation and antimicrobial defense mechanisms, and identified key candidate genes, including PDE4B, JAK1, ETS1, EIF4A2, FCMR, IGKV4-1, and XPO7. These genes demonstrated substantial discriminatory capability, with an area under the curve ranging from 0.95 to 0.99, and were found to be functionally linked to immune system dysfunction, cytokine signaling, NF-κB activation, and a maladaptive stress response. These findings link MRONJ to systemic immune-inflammatory imbalance and translational stress disruption, offering novel insights and potential biomarkers for diagnosis and risk evaluation.

Long-term treatment with bisphosphonates is accompanied by an increased risk of medication-related osteonecrosis of the jaw (MRONJ). Currently, no clinically useful biomarkers for the predictive diagnosis of MRONJ are available. To investigate the potential key proteins involved in the pathogenesis of MRONJ, a proteomic LC-MS/MS analysis of saliva was performed. Differentially expressed proteins (DEPs) were analyzed using BiNGO, ClueGO, cytoHubba, MCODE, KEGG, and ReactomeFI software packages using Cytoscape platforms. In total, 1545 DEPs were identified, including 43 up- and 11 down-regulated with a 1.5-fold cut-off value and adj. p-value < 0.05. The analysis provided a panel of hub genes, including APOA2, APOB, APOC2, APOC3, APOE, APOM, C4B, C4BPA, C9, FGG, GC, HP, HRG, LPA, SAA2-SAA4, and SERPIND1. The most prevalent terms in GO of the biological process were macromolecular complex remodeling, protein–lipid complex remodeling, and plasma lipoprotein particle remodeling. DEPs were mainly involved in signaling pathways associated with lipoproteins, the innate immune system, complement, and coagulation cascades. The current investigation advanced our knowledge of the molecular mechanisms underlying MRONJ. In particular, the research identified the principal salivary proteins that are implicated in the onset and progression of this condition.

Background: Dental caries disease is a dynamic process with a multi-factorial etiology. It is manifested by demineralization of enamel followed by damage spreading into the tooth inner structure. Successful early diagnosis could identify caries-risk and improve dental screening, providing a baseline for evaluating personalized dental treatment and prevention strategies. Methodology: Salivary proteome of the whole unstimulated saliva (WUS) samples was assessed in caries-free and caries-susceptible individuals of older adolescent age with permanent dentition using a nano-HPLC and MALDI-TOF/TOF mass spectrometry. Results: 554 proteins in the caries-free and 695 proteins in the caries-susceptible group were identified. Assessment using bioinformatics tools and Gene Ontology (GO) term enrichment analysis revealed qualitative differences between these two proteomes. Members of the caries-susceptible group exhibited a branch of cytokine binding gene products responsible for the regulation of immune and inflammatory responses to infections. Inspection of molecular functions and biological processes of caries-susceptible saliva samples revealed significant categories predominantly related to the activity of proteolytic peptidases, and the regulation of metabolic and catabolic processes of carbohydrates. Conclusions: Proteomic analysis of the whole saliva revealed information about potential risk factors associated with the development of caries-susceptibility and provides a better understanding of tooth protection mechanisms.