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Identification of Potential Biomarkers and Small Molecule Drugs for Bisphosphonate-Related Osteonecrosis of the Jaw
Kumarendran Balachandran1, Roszalina Ramli2, Saiful Anuar Karsani3
1Department of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.
Abstract:
This study aimed to identify potential molecular mechanisms and therapeutic targets for bisphosphonate-related osteonecrosis of the jaw (BRONJ), a rare but serious side effect of bisphosphonate therapy. This study analyzed a microarray dataset (GSE7116) of multiple myeloma patients with BRONJ (n = 11) and controls (n = 10), and performed gene ontology, a pathway enrichment analysis, and a protein-protein interaction network analysis. A total of 1481 differentially expressed genes were identified, including 381 upregulated and 1100 downregulated genes, with enriched functions and pathways related to apoptosis, RNA splicing, signaling pathways, and lipid metabolism. Seven hub genes (FN1, TNF, JUN, STAT3, ACTB, GAPDH, and PTPRC) were also identified using the cytoHubba plugin in Cytoscape. This study further screened small-molecule drugs using CMap and verified the results using molecular docking methods. This study identified 3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo[d]isoxazol-6-yl) methoxy) phenyl) propanoic acid as a potential drug treatment and prognostic marker for BRONJ. The findings of this study provide reliable molecular insight for biomarker validation and potential drug development for the screening, diagnosis, and treatment of BRONJ. Further research is needed to validate these findings and develop an effective biomarker for BRONJ.
Insights
Researchers identified key molecular mechanisms and potential drug targets for bisphosphonate-related osteonecrosis of the jaw (BRONJ). A novel compound shows promise as a treatment and prognostic marker for this condition.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Bisphosphonate therapy can lead to bisphosphonate-related osteonecrosis of the jaw (BRONJ), a severe complication.
- Understanding the molecular underpinnings of BRONJ is crucial for developing effective treatments.
Purpose of the Study:
- To identify molecular mechanisms and therapeutic targets for BRONJ.
- To screen for potential small-molecule drugs for BRONJ treatment.
Main Methods:
- Analysis of microarray data (GSE7116) from multiple myeloma patients with and without BRONJ.
- Gene ontology, pathway enrichment, and protein-protein interaction network analyses.
- Small-molecule drug screening using Connectivity Map (CMap) and molecular docking.
Main Results:
- Identified 1481 differentially expressed genes, with functions enriched in apoptosis, RNA splicing, signaling, and lipid metabolism.
- Seven hub genes (FN1, TNF, JUN, STAT3, ACTB, GAPDH, PTPRC) were identified.
- A novel compound, 3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo[d]isoxazol-6-yl) methoxy) phenyl) propanoic acid, was identified as a potential therapeutic agent.
Conclusions:
- This study provides molecular insights into BRONJ pathogenesis.
- The identified compound represents a potential therapeutic strategy and prognostic marker for BRONJ.
- Further validation is required for biomarker development and clinical application.
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