ABSTRACT Introduction: Periodontitis is a chronic inflammatory disease initiated by microbial dysbiosis and perpetuated by an aberrant host immune response, resulting in the progressive destruction of the tooth-supporting tissues. Neutrophils are essential for periodontal homeostasis; however, their dysregulated activation contributes to excessive inflammation and tissue damage. This narrative review aimed to critically evaluate the role of rat sarcoma virus gene-related C3 botulinum toxin substrate (RAC) genes, particularly RAC1 and RAC2, in neutrophil-mediated periodontal pathogenesis. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar databases. Studies exploring the molecular, cellular, and experimental roles of RAC1 and RAC2 in immune regulation, neutrophil function, oxidative stress, and periodontal disease progression were included and critically analyzed. Results: Changes in RAC1 and RAC2 activity were linked to overactive neutrophils, showing increased movement, higher reactive oxygen species production, and continuous release of inflammatory mediators. This heightened neutrophil response was associated with increased osteoclast activity and greater alveolar bone loss. Discussion: Collectively, altered RAC signaling plays a key role in neutrophil-mediated periodontal inflammation and tissue destruction. RAC1 and RAC2 exhibit both protective and pathogenic effects, depending on the context and duration of activation. Understanding this balance may help identify novel host-modulatory therapeutic targets and enable the development of RAC-based biomarkers for improved periodontal diagnosis and management.
Naidu et al. (Thu,) studied this question.