Proteomic pipeline to identify age-related compositional and structural changes of the human dentin extracellular matrix

Abstract

Aging is the conjunction of progressive physiological changes that occur in living organisms over time. A fundamental component of organs and tissues that undergoes functional and structural modifications with age is the extracellular matrix (ECM). The ECM is a dynamic assembly of proteins that regulates cellular functions and participates in tissue organization and remodeling. The ECM of teeth is no different but lacks turnover capability. Dentin, the bulk of the tooth, endures modifications throughout a lifespan. As of now, the composition of the dentin ECM and how it changes with age is unknown. To address, we used proteomics to profile the dentin ECM of young and older adult human teeth. We report the identification of 341 unique ECM proteins and define the matrisome of young and old dentin as composed of 125 and 112 proteins, respectively. Our study identified over 100 ECM proteins that have not previously been associated with the dentin. Importantly, it also reveals changes to both protein solubility and matrisome composition as a function of age. Our study is a first step towards the discovery of biomarkers of the aging tooth and the development of strategies to maintain or regenerate a healthy dentition in our aging population.

Identification of an Altered Matrix Signature in Kidney Aging and Disease

“…We also found a reduction in BM components and increased collagen VI and nephronectin in the aged glomerular matrix. Indeed, these components were also increased in proteomic studies of IgA nephropathy (11), DKD (12) and collagen VI was also upregulated in aged human dentin (49). A Nephroseq analysis provided further correlation between matrix signature proteins and transcriptional change in a variety of glomerular phenotypes.…”