Autophagic Activity and Aging in Human Odontoblasts

Abstract

Odontoblasts are long-lived post-mitotic cells in the dental pulp, whose function is to form and maintain dentin. The survival mechanisms that preserve the viability of terminally differentiated odontoblasts during the life of a healthy tooth have not been described. In the present study, we characterized the autophagic-lysosomal system of human odontoblasts with transmission electron microscopy and immunocytochemistry, to analyze the mechanisms that maintain the functional viability of these dentinogenic cells. Odontoblasts were found to develop an autophagic-lysosomal system organized mainly by large autophagic vacuoles that are acid-phosphatase-positive to various degrees. These vacuoles expressed the autophagosomal and lysosomal markers LC3 and LAMP2, respectively, in an age-related pattern indicating the organization of a dynamic autophagic machinery. Progressive accumulation of lipofuscin within lysosomes indicates reduced lysosomal activity as a function of odontoblast aging. Our results suggest that autophagic activity in odontoblasts is a fundamental mechanism to ensure turnover and degradation of subcellular components. A reduction in the efficacy of this system might compromise cell viability and dentinogenic secretory capacity. In adult teeth, this condition is described as an 'old odontoblast' stage.

Assessing biological aging: the origin of deficit accumulation

“…The mechanisms by which recovery occurs are complex and involve a number of processes, at different levels of the organism, from the DNA repair response (Moskalev et al 2012), to repair of chromosomal damage (Nicholls et al 2011) to autophagy (Couve and Schmachtenberg 2011; Fortini and Dogliotti 2010; Vicencio et al 2008), degradation of repair capacity (Koga et al 2011), and a host of others (Tacutu et al 2010b; Howlett and Rockwood 2013; Yashin et al 2013). This multiplicity of specific mechanisms responsible for age-related decline in the recovery rate likely corresponds to decline in flexibility (Fabre et al 2007) or loss of stress resistance with aging seen with decline in allostatic adaptation (Yashin et al 2007b, c, 2013).…”

Increased autophagic activity in senescent human dental pulp cells

“…The current study revealed that autophagy is activated in DPCs senescence in vitro . On the other hand, a reduction of autophagic activity in the odontoblast of old patients has been shown in dentine–pulp complex semithin sections (Couve & Schmachtenberg 2011). It is conceivable that autophagy has different roles in the different stages, or contexts, of ageing.…”

“…2008, Tang & Watkins 2008). Moreover, it has been reported that autophagic activity is a fundamental mechanism to degrade damaged cellular components for odontoblasts (Couve & Schmachtenberg 2011). However, autophagic activity to date has focused only on odontoblasts, and other pulp cells need to be investigated.…”

Gene expression changes in bioceramic paste-treated human dental pulp cells

“…LAMP2 is a lysosomal marker expressed by the autophagic vacuoles that constitutes the autophagic-lysosomal system of odontoblasts (16). The decrease in LAMP2 expression is an indicator of an aging odontoblast, which is reflected by lipofuscin accumulation in lysosomal compartments.…”