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Medication-Related Osteonecrosis of the Jaw: A Systematic Review and a Bioinformatic Analysis
Galina Laputková1, Ivan Talian1, Vladimíra Schwartzová2
1Department of Medical and Clinical Biophysics, Faculty of Medicine, University of P. J. Šafárik, Trieda SNP 1, 040 11 Košice, Slovakia.
Abstract:
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.
Insights
This study identified key genes, microRNAs, and cytokine pathways involved in medication-related osteonecrosis of the jaw (MRONJ). These findings advance understanding of MRONJ etiology and potential therapeutic targets.
Area of Science:
- Biomedical research
- Genomics
- Molecular biology
Background:
- Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of anti-resorptive and anti-angiogenic therapies.
- The precise etiology of MRONJ remains incompletely understood, necessitating further investigation into its molecular underpinnings.
Approach:
- A systematic literature review identified 12 human studies investigating genes, proteins, and microRNAs associated with MRONJ.
- Bioinformatic analyses were performed using multiple software packages and web platforms to construct molecular interaction networks.
- The Cochrane Collaboration risk assessment tool was employed to evaluate study quality.
Key Points:
- Analysis revealed 824 differentially expressed genes/proteins (DEGs) and 22 microRNAs implicated in MRONJ.
- A significant interactome emerged, highlighting 17 hub genes and specific microRNAs (e.g., hsa-mir-16-1, hsa-mir-21).
- Cytokine pathways were prominently identified in both hub DEGs and gene-miRNA interactions.
Conclusions:
- This research elucidates a panel of key genes, microRNAs, and associated pathways contributing to MRONJ pathogenesis.
- The findings represent a significant advancement in comprehending the complex molecular mechanisms underlying MRONJ.
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