Abstract
Purpose
Molar-incisor hypomineralization (MIH) is a qualitative developmental defect of enamel that affects first permanent molars with or without affecting permanent incisors. We aimed to carry out a quantitative proteomics-based study to compare and evaluate proteins in sound and MIH-affected enamel.
Materials and methods
Ten blocks each of the MIH-affected enamel and sound enamel were processed and prepared for LC–MS/MS analysis. Label-free quantitation was carried out to evaluate the differentially expressed proteins in the two groups of samples.
Results
A significant increase in the number of proteins in MIH-affected enamel (50.3 ± 29.6) was observed compared to the sound enamel (21.4 ± 3.2). While proteins like collagens, α1-anti-trypsin, kallikrein-4 (KLK4), matrix metalloprotease-20 (MMP-20), alpha-2-macroglobulin, and alpha-2-HS-glycoprotein were upregulated in sound enamel, there was over-expression of albumin, calcium-binding proteins, anti-thrombin III, and dentin sialophosphoprotein (DSPP), along with proteins implicated in stress response and inflammatory processes in MIH.
Conclusion
We propose that altered biomechanical properties of the enamel in MIH samples arise due to (i) down-regulation of proteins contributing to collagen biosynthesis and fibril formation; (ii) an overall imbalance in required levels of proteases (KLK4 and MMP-20) and anti-proteases (anti-thrombin-III which inhibits KLK-4), essential for optimal mineralization; (iii) very low levels of alpha-2-macroglobulin with important consequences in enamel mineralization and amelogenesis; and (iv) increased albumin in MIH, preventing proper growth of hydroxyapatite crystals. Increased inflammatory component was also seen in MIH; however, whether inflammation is a cause or consequence of the poor mineralization process needs to be assessed.
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We would like to thank lab technician for their active contribution towards the present clinical study.
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UM contributed to conception, design, acquisition, analysis, interpretation and drafting, and critical revision of the manuscript. AG contributed to conception and design, analysis and interpretation, and critically revised the manuscript. MLG supervised the proteomics work, analyzed and interpreted data, edited the manuscript. KG contributed to the work flow, design, acquisition, analysis and interpretation of the proteomics work flow, and writing and critical revision of the manuscript. AK contributed to the conception and design. AKT assisted in sample preparation for proteomics, and contributed to analysis and interpretation of data. All the authors gave final approval and agree to be accountable for all aspects of the work.
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Mukhtar, U., Goyal, A., Luthra-Guptasarma, M. et al. Label-free quantitative proteomics reveals molecular correlates of altered biomechanical properties in molar incisor hypomineralization (MIH): an in vitro study. Eur Arch Paediatr Dent 23, 179–191 (2022). https://doi.org/10.1007/s40368-021-00687-2
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DOI: https://doi.org/10.1007/s40368-021-00687-2