Axin2-expressing cells differentiate into reparative odontoblasts via autocrine Wnt/β-catenin signaling in response to tooth damage

Abstract

In non-growing teeth, such as mouse and human molars, primary odontoblasts are long-lived post-mitotic cells that secrete dentine throughout the life of the tooth. New odontoblast-like cells are only produced in response to a damage or trauma. Little is known about the molecular events that initiate mesenchymal stem cells to proliferate and differentiate into odontoblast-like cells in response to dentine damage. The reparative and regenerative capacity of multiple mammalian tissues depends on the activation of Wnt/β-catenin signaling pathway. In this study, we investigated the molecular role of Wnt/β-catenin signaling pathway in reparative dentinogenesis using an in vivo mouse tooth damage model. We found that Axin2 is rapidly upregulated in response to tooth damage and that these Axin2-expressing cells differentiate into new odontoblast-like cells that secrete reparative dentine. In addition, the Axin2-expressing cells produce a source of Wnt that acts in an autocrine manner to modulate reparative dentinogenesis.

Molecular Programming of Perivascular Stem Cell Precursors

“…Having MSC precursors ready “primed” for odontoblast differentiation may be a way of achieving this. Significantly, we were unable to detect Dspp expression in molar pulp pericytes via qPCR or RNA‐seq which is consistent with these cells being in a quiescent state during homeostasis and only required to provide cells for new odontoblast formation following dentine damage (data not shown) . Overall, what was seen was that not only did ChIP‐seq results mirror the gene expression patterns observed in the RNA‐seq profiling but also provided insight into the distinct chromatin architecture in these pericytes that is driving a corresponding transcriptional output.…”

Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair

“…S4 ). Axin-2 plays an important role in the regulation of the stability of β-catenin in the Wnt signaling pathway which is critical to the reparative and regenerative capacity of multiple tissues 21 , 22 . Axin-2 mRNA expression was significantly upregulated at days 30 and 60 following doxorubicin treatment (* P < 0.05), consistent with myocardial regeneration in response to injury.…”

A new perspective to push forward a stagnated dental world

“…We found that via the understanding of a signalling cascade called 'Wnt' , we could manipulate dentine repair. 6 From the basic biological knowledge gained, we were able to translate this inner biological capacity into a novel treatment approach. We showed that by adding small molecules capable of activating this genetic cascade, we increased reparative and reactionary dentine secretion in the dental pulp, which has the potential to increase the vitality of teeth with large damaged areas.…”