Obesidade, doença periodontal e células de Schwann: em busca de novos caminhos

Abstract

There is a bidirectional association between highly prevalent oral diseases and metabolic diseases, with obesity being a significant risk factor for periodontal disease (PD). Schwann cells (SCs) and glial progenitors are responsible for detecting the first signs of tissue alteration and can repair damaged tissues. Understanding the role of these cells in the healthy periodontal ligament and in PD could provide new therapeutic possibilities for periodontal alterations associated with obesity. This study investigated the relationship between obesity, PD, and SC using PLP1-CreERTdTomato transgenic mice (PLP1+; myelinated SCs), and explored, in vitro, the effect of different inflammation scenarios on the cellular functions of two non-myelinated Schwann cell lines (SW-10; RT4-D6P2T) and periodontal ligament cells (PDLC). Obesity was induced in transgenic or WT (wild-type) mice through a high-fat diet for 12 weeks. The murine model of ligature-induced PD was also used. In another group, obese mice were also induced to PD. Mice maintained on a conventional diet and without ligature served as the control group. At the end of the experimental period, the animals were euthanized, and the maxillae were collected and processed for microtomography, confocal microscopy, routine histology, and quantitative PCR (q-PCR). In vitro, PDLC and CS (SW-10) were stimulated with lipopolysaccharide (LPS) from Escherichia coli and Interferon-Gamma (IFNɣ) and evaluated for viability, migration, gene expression of inflammatory markers, and osteodifferentiation. CS (RT4-D6P2T) were stimulated with LPS from Porphyromonas gingivalis and with adipose tissue-conditioned medium (ATCM) from Wistar rats and analyzed for viability, migration, and osteogenic and adipogenic differentiation. In vivo, micro-CT imaging demonstrated that obesity exacerbates the severity of PD, resulting in significant bone resorption. Confocal microscopy and qPCR confirmed an increase in Plp1+ cells in the affected region, with increased gene expression in the presence of obesity, associated with or without PD. Concomitant with the high expression of Plp1, we observed a decrease in Pparɣ gene expression in the obese and PD groups, as well as a reduction in p38 expression in both the obese and PD groups. The gene expression of Tnf and Runx-2 remained stable in all experimental groups. The presence of inflammatory infiltrate, as well as characteristic periodontal pocket and disorganized periodontal ligament alterations, was verified in the PD groups. In vitro, in the presence of E. coli LPS and IFNɣ, PDLCs express more genes related to inflammation and have a greater mineralization capacity when compared to SW-10s. CS (RT4-D6P2T) are not affected by LPS treatment with P. gingivalis, but rather by the presence of ATCM, while preserving the capacity for osteogenic and adipogenic differentiation. The findings indicate that the hyperinflammatory and lipotoxic microenvironment of obesity, associated or not with PD, alters the dedifferentiation capacity of CS, both in the presence and absence of PD, thus inhibiting their repair phenotype.