Saliva proteomic patterns in patients with molar incisor hypomineralization

Abstract

Molar incisor hypomineralization (MiH) is an endemic pediatric disease with an unclear pathogenesis. considering that saliva controls enamel remineralization and that MiH is associated with higher saliva flow rate, we hypothesized that the protein composition of saliva is linked to disease. To test this, we enrolled 5 children aged 6-14 years with MIH showing at least one hypersensitive molar and 5 cariesfree children without hypomineralization. Saliva samples were subjected to proteomic analysis followed by protein classification in to biological pathways. Among 618 salivary proteins identified with high confidence, 88 proteins were identified exclusively in MIH patients and 16 proteins in healthy controls only. Biological pathway analysis classified these 88 patient-only proteins to neutrophil-mediated adaptive immunity, the activation of the classical pathway of complement activation, extracellular matrix degradation, heme scavenging as well as glutathione-and drug metabolism. The 16 controlsonly proteins were associated with adaptive immunity related to platelet degranulation and the lysosome. This report suggests that the proteaneous composition of saliva is affected in MIH patients, reflecting a catabolic environment which is linked to inflammation. The term molar incisor hypomineralization (MIH) was coined in 2001 and defines a qualitative enamel defect affecting one or more first permanent molars with or without the involvement of permanent incisors 1. The global prevalence of MIH exceeds one-tenth of children, ranging from 0.5% to 40.2% and differing between countries 2. Demarcated hypomineralized enamel lesions are caused by the process of amelogenesis being altered or interrupted 3. Compared to normal teeth, affected enamel is characterized by a reduction in mineral quantity and quality, increased porosity and reduced hardness 4. The clinical management of MIH is challenging because of rapid wear, progressing enamel loss, increased susceptibility to caries, loss of fillings, and severe hypersensitivity 5. Although MIH is a pandemic pediatric disease, the etiology remains unknown 6. Several hypotheses are proposed, including childhood illness, genetic influences 7,8 , and a putative individual threshold of susceptibility 3. Thus, there is an increasing demand to better understand the cause and consequence(s) of MIH at the cellular and molecular level. Chronic subclinical pulpal inflammation is a consequence of increased enamel porosity and reduced hardness in MIH 9. Pulpitis is characterized by enhanced neutrophil emigration into the pulp tissue 10,11 and biomarkers can be identified in gingival crevicular fluid 12. Moreover, in periodontitis patients, neutrophils constantly migrate through the oral epithelia into the saliva 13 , with increasing numbers exhibiting apoptosis and augmented levels of degranulation markers 14. Further, saliva of MIH patients reportedly displays altered physicochemical properties such as altered flow rates, viscosity, pH and acid buffering capacity 15. Thus, it is conceivabl...

Proteomic Analysis of Porcine-Derived Collagen Membrane and Matrix

“…Highly sensitive mass spectrometers and improved separation methods have enabled analysis of minute sample amounts of proteins from a wider area of biological materials, such as plasma, serum, urine, bone, and saliva, just to name a few [ 25 , 26 , 27 , 28 , 29 ]. Furthermore, the use of proteomics enables the nature of interactions between biomaterials and biological systems to be determined, e.g., for tissue-biomaterials or cell-biomaterials [ 30 ].…”

Amelogenesis Imperfecta Enamel Changes, Amelogenin, and Dental Caries Susceptibility

“…Proteins exclusively found in saliva of individuals with MIH include pathways for neutrophil-mediated adaptive immunity, the activation of the classical pathway of complement activation, extracellular matrix degradation, heme scavenging as well as glutathione and drug metabolism. In comparison, individuals without MIH had proteins that belong to adaptive immunity related to platelet degranulation and the lysosome (27).…”

Analysis of Human and Microbial Salivary Proteomes in Children Offers Insights on the Molecular Pathogenesis of Molar-Incisor Hypomineralization

“…As changes in saliva composition are associated with oral pathologies, it is reasonable to assume that the saliva proteome of MIH-affected children might be altered compared to healthy children. While several studies have attempted to identify proteomic profiles in oral diseases [ 16 ], there are only scarce data in the literature about the proteome in MIH pathology, indicating differential expression of proteins in MIH patients’ saliva [ 17 ].…”