Ativação do receptor P2X7 inibe osteoblastos e induz perda óssea na periodontite experimental

Abstract

Periodontitis is an immunoinflammatory disease with a high worldwide prevalence that affects the supporting tissues, especially the periodontal ligament and alveolar bone. The presence of periodontopathogens is an important etiological factor, but the host's response to the dysbiotic biofilm is a determining factor in its onset and progression. The exacerbation of inflammation leads to tissue destruction, which induces the release of ATP, which interacts with purinergic receptors, especially P2X7R. P2X7R is widely expressed in immune and bone cells and has therefore been linked to inflammatory bone diseases. Studies highlight its effect on osteoclasts more than on osteoblasts, but little has yet been said about the role of P2X7R in periodontitis. Therefore, this study aimed to evaluate the role of P2X7R in experimental periodontitis in rats and the effect of its modulation on osteoblasts. Initially, an in vitro assay was carried out in order to assess the expression of P2X7R in cells and the effect of modulators of this receptor on the proliferation and morphology of osteoblasts (OFCOL II strain), as well as to determine alkaline phosphatase levels. Wistar rats were then used to induce experimental periodontitis by ligation. The animals were randomly divided into 4 groups (n=6): (1) naive group; (2) periodontitis group (PE), receiving 1 ml of 0.9% saline solution ip; (3) BzATP group, receiving BzATP, a P2X7R agonist, at a dose of 1 mg/kg/day, ip. (4) BBG group, receiving BBG, a P2X7R antagonist, at a dose of 45.5 mg/kg, ip; except for the naive group, all the animals underwent PE. On the 11th day, all the animals were euthanized and the maxillae removed for microscopic analysis, and blood samples were taken for alkaline phosphatase (AP). The results of this study showed that P2X7R was expressed in vitro and that activation of P2X7R reduces the viability of osteoblasts and alters their morphology (p<0.05). In the animals subjected to periodontitis, activation of the P2X7 receptor altered the architecture of the periodontal tissue with an intense inflammatory infiltrate and disorganization of the periodontal ligament fibres, similar to the animals in the SAL group. BzATP reduced the number and function of osteoblasts in periodontal tissue (P<0.05). P2X7 receptor blockade was able to improve periodontal architecture and attenuate the local inflammatory infiltrate. The use of BBG in animals with periodontitis caused an increase in the number of osteoblasts and in FAO levels when compared to animals in the SAL group. In short, the results of this study suggest that P2X7R is involved in periodontal inflammatory bone loss, affecting the viability of osteoblasts, and that it could be a potential pharmacological target for the treatment of periodontitis.