Ligation of P2X₇ receptors with a ‘danger signal’, extracellular ATP (eATP), has recently been shown to result in production of intracellular reactive‐oxygen‐species (ROS) in macrophages. We show that primary gingival epithelial cells (GECs) produce sustained, robust cellular ROS upon stimulation by eATP. The induction of ROS was mediated by P2X₇ receptor signalling coupled with NADPH‐oxidase activation, as determined by pharmacological inhibition and RNA interference. Furthermore, Porphyromonas gingivalis, an oral opportunistic pathogen, upregulated the antioxidant glutathione response, modulated eATP‐induced cytosolic and mitochondrial ROS generated through P2X₇/NADPH‐oxidase interactome, and subsequently blocked oxidative stress in GECs via temporal secretion of a P. gingivalis effector, nucleoside‐diphosphate‐kinase (Ndk). An ndk‐deficient P. gingivalis mutant lacked the ability to inhibit ROS production and persist intracellularly following eATP stimulation. Treatment with recombinant Ndk significantly diminished eATP‐evoked ROS production. P. gingivalis infection elicited a strong, time‐dependent increase in anti‐oxidativemitochondrial UCP₂ levels, whereas ndk‐deficient mutant did not cause any change. The results reveal a novel signalling cascade that is tightly coupled with eATP signalling and ROS regulation. Ndk by P. gingivalis counteracts these antimicrobial signalling activities by secreting Ndk, thus contributing to successful persistence of the pathogen.

Theofilos Koutouzis, DDS, MS/Rodrigo Neiva, DDS, MS/Madhu Nair, DDS, PhD/J?rg Nonhoff, DDS, PhD/Tord Lundgren, DDS, PhD: Purpose: The aim of this study was to evaluate marginal bone levels, with cone beam computed tomography, on the buccal and lingual aspects of implants placed with the implant-abutment interface (IAI) at different positions in relation to the alveolar crest. Materials and Methods: Thirty patients in need of single-tooth rehabilitation were randomly assigned to three groups based on the position of the IAI in relation to the buccal aspect of the alveolar crest at the time of implant placement. Patients in groups 0, 1, and 2 had their implants placed level with the buccal crest or 1 or 2 mm apical to the buccal aspect of the alveolar crest, respectively. The implants were restored with screw-retained single crowns after 4 months. Marginal bone levels on the buccal and lingual aspects of the implants were evaluated at 12 months after implant placement. Results: All groups of implants demonstrated significantly different crestal positions. Group 2 implants maintained the greatest subcrestal position (1.33 ? 0.86 mm) compared to the implants of group 0 (?0.04 ? 0.18 mm) and group 1 (0.34 ? 0.44 mm). There were no differences between groups in the level of the first bone-to-implant contact relative to the implant platform. Implants of group 0 exhibited less buccal bone remodeling (?0.08 ? 0.25 mm) compared to group 1 (?0.65 ? 0.45 mm) and group 2 (?0.85 ? 0.75 mm) implants. For groups 1 and 2 implants, there was a significant negative correlation between buccal wall thickness following the osteotomy and the amount of buccal bone remodeling. Conclusion: In this study, different responses were seen in the buccal and lingual peri-implant bone for implants with platform-switched Morse taper connections placed with the IAI at different locations in relation to the alveolar crest.