Journal of periodontal research最新文献

Periodontitis and noncommunicable diseases share an overall inflammatory state often sustained by concomitant oxidative stress as one of the main processes involved. A huge amount of literature supports such a main pathogenic process, which is also considered the therapeutic target. The attempt to control inflammation by acting on oxidative stress has given largely unsatisfactory results, either as preventive or as treatment approaches. To propose new ideas that will help in this field, the paper reviewed all physiological processes involved in oxidative stress in periodontitis. The discussion considers all of them, considering whether they come from endogenous sources, that is, all the intracellular physiological devices and/or processes that are involved in oxidative stress, such as mitochondria, rough endoplasmic reticulum, peroxisomes, autophagy, and aging, or from exogenous sources, that is, the external factors that affect oxidative stress, such as nutrition, physical activity, psychological status, environmental conditions, microbiome, and drugs. The most important conclusion is that all of them should be taken into consideration in future research since we need to address oxidative stress as part of a specific biological and metabolic cellular state in a multicellular organism. To understand the cellular physiology that underlies oxidative stress and consider this point in treating each of our periodontal patients according to a specific oxidative state could be called personalized/precise oxidative stress therapy (POST) and should include the following points: (1) environmental conditions, (2) individual characteristics, and (3) oxidative state of different intracellular organelles.

The central question addressed in this review revisits the historical chicken-and-egg debate: "In periodontitis, does microbial dysbiosis drive inflammation, or does inflammation shape the subgingival microbiome?" This question is reframed through the lens of inflammation resolution. Specialized pro-resolving mediators (SPMs) provide a mechanistic framework for understanding how inflammation intersects with microbial dysbiosis. Derived from omega-3 and omega-6 fatty acids, SPMs actively promote the resolution of inflammation through binding of specific cell surface receptors rather than nonspecifically suppressing it, highlighting their therapeutic potential as side-effect-free host modulators, with implications beyond periodontitis to other chronic inflammatory diseases. The evidence reviewed shows how SPMs can: (1) control inflammation by resolution rather than inhibition, (2) reverse microbial dysbiosis as a consequence of inflammation control, and (3) promote tissue regeneration through diverse biological pathways. Whether the primary dysregulation in periodontitis lies solely in resolution failure or involves additional-possibly still unidentified-mechanisms, remains unclear. All individuals harbor periodontal pathobionts, yet only a subset develop severe disease. Why do some individuals with significant biofilm accumulation maintain attachment levels, while others with reasonable plaque control become edentulous? This remains one of the most significant unanswered questions in periodontology. What is evident, however, is the need for a paradigm shift. While bacteria initiate the inflammatory process in all individuals, it is the host response that ultimately determines the progression to periodontitis.

Periodontitis is a widespread inflammatory disease of the oral cavity that is influenced by genetic and environmental factors. Periodontitis has a high heritability, and particularly severe periodontitis often manifests before the age of 40, suggesting a strong genetic component. Genetic research has identified genetic variants associated with susceptibility to periodontitis that provide insights into the underlying mechanisms, which may improve future diagnostic and treatment strategies. We screened potential risk single-nucleotide variants (SNVs) identified in genetic association studies on periodontitis using the following selection criteria: genome-wide significance (p ≤ 5 × 10^-8) or suggestive significance (p ≤ 5 × 10^-6) with replication in ≥ 1 independent study. Additionally, we included SNVs with p < 5 × 10^-4 and ≥ 2 independent replications and functional validation. Due to the polygenic nature of periodontitis, we prioritized common variants with a minor allele frequency ≥ 1% and included rare variants (MAF ≤ 0.001) identified in whole-exome sequencing studies of severe cases with early onset. These criteria increased the reliability of identifying true genetic risk factors. The identified genetic risk loci for periodontitis can be primarily attributed to two biological functions: immune response and tissue integrity including regeneration. Genes such as SIGLEC5, DEFA1, FCERG1, PPBP/CXCL5/PF4, CDKN2B-AS1, and CTSC have a known function in neutrophil activity, antimicrobial defense, and mediation of the immune response. In particular, SIGLEC5, PLG, RSPO4, ROBO2, HMCN2, and CTSC appear to contribute to wound healing, extracellular matrix remodeling, and hemostasis. In particular, SIGLEC5, PLG, and PPBP/PF4 interact at the interface of immune function and tissue repair. In conclusion, risk genes for periodontitis point to the importance of the interplay between immune response and tissue homeostasis in the etiology of periodontitis. Future large-scale genome-wide association studies, whole-exome sequencing, and functional studies will likely uncover additional risk genes and refine our understanding of genetic contributions to periodontitis and help to develop potential therapeutic targets.

Although tissue engineering and cell therapy have been widely investigated as promising regenerative modalities, their clinical translation has partly been limited by a lack of standardization, high costs, and regulatory barriers. Recently, cell-free therapies (CFT) in the form of cell secretomes [conditioned media (CM)] and extracellular vesicles (EVs) have emerged as viable alternatives to cell therapies. However, much of the evidence is based on preclinical studies. This scoping review aimed to summarize the current evidence for using human-derived CFT, with a focus on EVs, for craniofacial regeneration. Based on predefined inclusion criteria and a systematic search covering three electronic databases (MEDLINE, EMBASE, Web of Science), 122 animal studies (n = 27 CM, n = 95 EVs), and 4 clinical studies (n = 2 CM, n = 2 EVs), mostly reporting on bone and periodontal regeneration, were included. The use of oral-derived CFT, particularly from the periodontal ligament, dental pulp, and gingiva, was frequently reported. A wide range of pre-conditioning strategies, dosages, and delivery methods were tested. The preclinical data revealed a clear adjunctive benefit of CFT with biomaterial scaffolds versus scaffolds alone for bone and periodontal regeneration. Limited clinical data based on small patient groups confirmed the safety and feasibility of CFT, although robust evidence for efficacy is lacking. Finally, several issues related to the clinical translation of CFT have been highlighted for future consideration.

Periodontal and craniofacial regeneration presents significant challenges owing to the complex tissue architecture, inadequate vascularization, and diminished stem cell populations within damaged tissues. Traditionally, autologous bone grafts or alternative bone substitute materials have been employed to address these conditions; however, these approaches are constrained by donor site morbidity, limited availability, and suboptimal regenerative efficacy. The advancement of mesenchymal stem/stromal cell (MSC) biology has accelerated the development of cell-based therapies in modern dentistry, which now focuses on biologically driven approaches to regenerate tissues. MSC-based therapies currently under investigation, both preclinically and clinically, show promise for improving tissue integration and healing processes of both soft and hard tissues, attributable to their multipotent nature, immunomodulatory properties, and paracrine signaling capabilities. Nevertheless, obstacles persist, including inconsistent standardization, limited scalability, regulatory hurdles, a paucity of controlled studies, and restricted biomaterial options. This review evaluates MSC-based treatments for periodontal and craniofacial reconstruction by discussing recent research findings and existing obstacles. This review also examines future prospects, such as advanced biofabrication methods, including 3D printing and bioprinting, which have the potential to improve personalized cell therapy for periodontal and craniofacial regeneration.

Salivary circular RNAs, particularly hsa_circ_0003563 (circRUNX2) and hsa_circ_0001161 (circMMP9), show strong potential as non-invasive biomarkers for diagnosing periodontitis and distinguishing the rate of disease progression, offering promising tools for improved periodontal diagnostics.