» Articles » PMID: 39596473

Insights into Medication-Induced Osteonecrosis of the Jaw Through the Application of Salivary Proteomics and Bioinformatics

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2024 Nov 27
PMID 39596473
Authors
Affiliations
Soon will be listed here.
Abstract

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 . -value < 0.05. The analysis provided a panel of hub genes, including , , , , , , , , , , , , , , , and . 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.

References
1.
Antonuzzo L, Lunghi A, Petreni P, Brugia M, Laffi A, Giommoni E . Osteonecrosis of the Jaw and Angiogenesis inhibitors: A Revival of a Rare but Serous Side Effect. Curr Med Chem. 2017; 24(28):3068-3076. DOI: 10.2174/0929867324666170511113811. View

2.
Tollefsen D . Heparin cofactor II modulates the response to vascular injury. Arterioscler Thromb Vasc Biol. 2006; 27(3):454-60. DOI: 10.1161/01.ATV.0000256471.22437.88. View

3.
Querrer R, Ferrare N, Melo N, Stefani C, Reis P, Mesquita C . Differences between bisphosphonate-related and denosumab-related osteonecrosis of the jaws: a systematic review. Support Care Cancer. 2020; 29(6):2811-2820. DOI: 10.1007/s00520-020-05855-6. View

4.
Balachandran K, Ramli R, Karsani S, Abdul Rahman M . Identification of Potential Biomarkers and Small Molecule Drugs for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ): An Integrated Bioinformatics Study Using Big Data. Int J Mol Sci. 2023; 24(10). PMC: 10218302. DOI: 10.3390/ijms24108635. View

5.
Kim J, Yeon A, Parker S, Shahid M, Thiombane A, Cho E . Alendronate-induced Perturbation of the Bone Proteome and Microenvironmental Pathophysiology. Int J Med Sci. 2021; 18(14):3261-3270. PMC: 8364444. DOI: 10.7150/ijms.61552. View