Abstract
Periodontitis is a chronic inflammatory disease that compromises the periodontium and is among the most prevalent oral conditions worldwide. Recent studies highlight exosomes - small extracellular vesicles carrying nucleic acids, lipids, metabolites, and proteins - as key mediators of intercellular communication contributing to disease progression. The objective of this review was to systematically analyze the existing scientific literature regarding the role of exosomes in the pathogenesis of periodontitis. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The study question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: "Do exosomes contribute to the pathogenesis of periodontitis?". A literature search was performed in PubMed and ScienceDirect databases for articles published between 2015 and 2025. Inclusion criteria were restricted to original research, written in English, involving human participants or human-derived samples that explicitly focused on exosomes in the context of periodontitis. Out of 1,000 identified records, 106 full-text articles were screened, and six met the inclusion criteria. The included studies investigated salivary, gingival, or periodontal ligament stem cell-derived exosomes and reported their roles in pyroptosis, macrophage polarization, angiogenesis, and immune modulation. Key findings demonstrated that the downregulation of exosomal miR-223-3p enhanced NLRP3-mediated pyroptosis, while exosomal miR-143-3p promoted M1 macrophage polarization via the PI3K/AKT/NF-κB signaling pathway. In addition, exosomal VEGFA regulated by miR-17-5p promoted angiogenesis, and salivary exosomes exhibited immune-related protein cargo, decreased tetraspanins (CD9, CD81), and elevated PD-L1 mRNA in advanced disease. Collectively, this review underscores the ability of exosomes to transport diverse molecular cargo and influence recipient cell behavior, highlighting their role as mediators of intercellular communication in periodontal inflammation.