Blockage of P2X7 receptor activation attenuated bone loss in ligature-induced model of periodontitis in rats.

Abstract

Periodontitis is a highly prevalent immunoinflammatory disease that compromises the supporting tissues of the teeth, especially the periodontal ligament and alveolar bone. During disease progression, inflammatory responses lead to the release of ATP, which interacts with purinergic receptors such as P2X7R, potentially influencing bone remodeling. Although P2X7R has been studied in bone cells, its specific role in periodontitis remains poorly characterized. This study aimed to evaluate the effects of P2X7R modulation on osteoblastic activity and experimental bone loss. In vitro, P2X7R expression was confirmed in OFCOL II osteoblastic cells. Receptor activation using BzATP significantly reduced cell viability, altered cell morphology, and decreased alkaline phosphatase (ALP) activity (p < 0.05). In vivo, periodontitis was induced in Wistar rats via ligature. Animals were allocated into four groups: (1) Naïve; (2) Periodontitis (saline-treated); (3) BzATP-treated (P2X7R agonist); and (4) BBG-treated (P2X7R antagonist). BzATP aggravated periodontal damage, with increased inflammation, loss of osteoblasts, and disorganization of periodontal ligament fibers. In contrast, BBG improved tissue architecture, reduced inflammatory infiltrate, and increased osteoblast numbers and ALP activity, possibly via the Wnt signaling pathway. These results suggest that P2X7R activation contributes to inflammation-driven bone loss, impairing osteoblast viability and function. Therefore, P2X7R inhibition may serve as a promising pharmacological strategy to preserve bone and periodontal integrity in the context of periodontitis.