Journal of periodontal research最新文献

Aim: To assess tissue perfusion changes and wound healing biomarker levels after root coverage procedures with coronally advanced flap in combination with the cross-linked xenogeneic collagen matrix (CCMX), loaded either with a placebo or recombinant human platelet-derived growth factor-BB (rhPDGF).

Methods: This study was designed as a secondary analysis from a previously published clinical trial, and it assessed the tissue perfusion changes over 6 months around multiple gingival recession defects, treated with either with CCMX alone (control) or with CCMX + rhPDGF (test). High frequency Doppler ultrasonography (HFUS) scans were obtained at sites of interest at baseline, 2 weeks, 3 months, and 6 months after surgery. Dynamic tissue perfusion measurements (DTPMs) were performed at the midfacial, interproximal, and transverse aspects of the teeth by an operator, blinded to treatment allocation, using a software package. The expression of different wound healing biomarkers from the gingival crevicular fluid was also assessed.

Results: The regression analyses showed similar tissue perfusion changes between the two groups throughout the majority of the 6 months. DTPMs at 2 weeks showed the test group to have significantly higher perfusion relief intensity (pRI, p < 0.001), mean perfused area (pA, p < 0.001), mean blood flow intensity (FI_mean, p = 0.021), and total blood flow intensity (FI_tot, p = 0.021) at the graft region of interest (ROI) compared to control sites. The test sites also exhibited significantly greater pA (p = 0.033) and blood flow intensity "blue" (FI_blue, meaning flow away from the transducer, p = 0.035) at the level of the flap compared to the control sites. At 2 weeks, FI_blue of the graft was directly correlated with the final mean root coverage (p = 0.008) and complete root coverage (p = 0.003). FI_mean and FI_tot of the graft exhibited a direct correlation with volume gain at 6 months (p = 0.031 for both parameters). The final GT gain was correlated to the early DTPMs (pA and FI_blue) of the graft and the flap. The two groups exhibited different expressions of IL-1β, PDFG-BB, and VEGF over 3 months, with the 1-week levels of PDGF-BB that were associated with time to recovery.

Conclusions: HFUS allowed exquisite assessment of tissue perfusion occurring at the entire surgical reconstructive regions and also within the flap and the graft. Sites treated with CCMX + rhPDGF exhibited higher DTPMs, primarily within the graft and flap ROIs at the 2-week timepoint compared to sites augmented with CCMX + saline. Early DTPMs at the graft and flap ROIs showed associations with PROMs and the final clinical outcomes.

Trial registration: ClinicalTrials.gov: NCT04462237.

Aim: To examine the association between the oral microbiome, periodontitis, and edentulism in a nationally representative sample of the U.S.

Population:

Methods: A total of 5299 adults aged 30-69 years were examined (NHANES 2009-2012). Oral rinse samples were collected and analyzed through 16S rRNA gene sequencing. Periodontitis presence, stage, extent, and grade were assessed according to the 2017 AAP/EFP classification using the ACES framework, with edentulism considered as a distinct category. Bacterial diversity and taxonomic composition were evaluated using alpha and beta diversity metrics and multivariable linear models (MaAsLin2), adjusted for relevant confounders.

Results: Alpha diversity increased with periodontitis severity, extent, and grade, peaking in Stage III generalized periodontitis. In Stage IV, extensive tooth loss was associated with a decrease in alpha diversity. Edentulous individuals exhibited the lowest alpha diversity, falling below levels observed in those without periodontitis. Beta diversity differences across periodontitis severity, extent, and grade were subtle (< 0.2%). Taxonomically, increasing severity, extent, and grade of periodontitis were associated with enrichment of established periodontitis-related genera (e.g., Dialister, Filifactor, Fusobacterium, Porphyromonas, Prevotella, Tannerella) and Jonquetella, alongside depletion of health-related genera (e.g., Rothia, Veillonella). A total of 13 genera were commonly altered in both edentulous individuals and those with Stage III-IV periodontitis, relative to participants with no or localized Stage I-II disease.

Conclusion: Periodontitis is characterized by an increase in alpha diversity with advancing severity, extent, and grade, followed by a decline with extensive tooth loss and edentulism. However, it accounted for only a small fraction of the overall variation in oral microbiome composition. Taxonomic shifts included enrichment of established periodontitis-related genera and Jonquetella, alongside depletion of health-related genera. The persistence of periodontitis-associated bacteria in edentulous individuals may have important implications for implant dentistry.

We have previously described Porphyromonas gingivalis as a keystone pathogen due to its critical contribution to the development of periodontitis. Healthy periodontal tissue contains an active innate host defense system made in response to commensal bacterial colonization that facilitates an orchestrated expression of protective host mediators. We designated P. gingivalis as a keystone pathogen since it impairs host defense, leading to the overgrowth of oral commensal bacteria, altering a protective host surveillance response to a destructive, increased host inflammatory response. In addition, P. gingivalis uncouples inflammation from bactericidal activity, which manipulates the host inflammatory response in a way that promotes bone loss but not bacterial clearance. In this review, we update the keystone hypothesis by summarizing recent key fields of research that enhance our understanding of the keystone properties of this organism. For example, the last decade has witnessed significant progress in the characterization of the mechanism of export of some of the critical virulence determinants of P. gingivalis via the type IX secretion system (T9SS). These include, but are not limited to, the gingipain proteases, hemagglutinins, and numerous other potential virulence factors that require further characterization. As an example, the secretion of P. gingivalis peptidylarginine deiminase (PPAD), which has been shown to neutralize human innate immune defenses, is exported via the T9SS. In addition, outer membrane vesicles (OMV) are increasingly recognized as effective long-distance vehicles of P. gingivalis virulence determinants to the external environment. Furthermore, OMVs have been shown to provide a novel delivery system for lipid A structures attached to the two lipopolysaccharides produced by this bacterium: O-LPS and A-LPS. Lipid A modifications by P. gingivalis represent a key patho-adaptation by modulating the host immuno-inflammatory response and providing protection from bacterial killing. Critically, it is also recognized that the full expression of the P. gingivalis keystone phenotype is strain-dependent and subject to environmental control, both of which may contribute to an individual's susceptibility to disease. These studies further validate and confirm the key contribution of P. gingivalis to the transition from periodontal health to disease.

Aim: To analyze the rate, timeline, and risk factors for furcation involvement (FI) progression using a large, multi-center electronic health record database.

Methods: This retrospective cohort study analyzed 3924 patients with periodontitis and at least 1 year of follow-up from the BigMouth Dental Data Repository. Furcation progression (increase in the maximum recorded furcation grade for a given tooth during the follow-up period) was assessed at both the patient and tooth level. Time-to-event analysis at the patient level was performed using Kaplan-Meier curves and a multivariate Cox Proportional Hazards model to identify predictive factors. At the tooth level, the primary analysis was a multilevel Cox model, with a Fine-Gray competing risks model performed as a secondary analysis to assess the impact of tooth loss.

Results: Over a mean follow-up of 4.7 years, 57.1% of patients experienced furcation progression, with a median time to the first event of 3.6 years. A Cox proportional hazards model identified smoking as the factor most strongly correlated with progression, increasing the risk by 51% (Hazard Ratio [HR]: 1.51), followed by high blood pressure (HR: 1.25) and diabetes (HR: 1.24). At the tooth level, the initial furcation grade showed the strongest association with progression, increasing the hazard by 3.05 times for each unit increase.

Conclusion: Furcation involvement is a progressive event for a majority of patients diagnosed with periodontitis. The risk of progression is correlated with a combination of systemic factors and the patient's overall periodontal status, but the factor most strongly correlated with a tooth's future deterioration is its own initial furcation grade.

This study identifies autophagy-pyroptosis crosstalk as a driver of periodontal pathogenesis and suggests ATG7 as a preliminary, context-dependent modulator.

Peri-implant diseases (PIDs) are highly prevalent and threaten both the success and longevity of implant-supported prostheses. Their prevention should begin before implant surgery (i.e., primordial prevention) by avoiding risk factor exposure and ensuring optimal implant placement conditions. Prehabilitation, a multimodal strategy already used in other surgical fields, can be applied to implant dentistry to optimize patient status before surgery. By addressing modifiable behavioral risk factors and strengthening systemic and local conditions, prehabilitation would enhance both short- and long-term outcomes of implant-supported rehabilitation.

In its most common form, periodontitis is viewed as a chronic immunoinflammatory disorder of the tooth supporting tissues, shaped by host-microbiome disequilibrium, exaggerated immune activation, and impaired resolution mechanisms. This review explores the periodontal battlefield through its inflammatory and immunological lens, beginning with the transformation of the lesion from silent immune surveillance to sustained inflammation, connective tissue degradation, and alveolar bone loss. The classical Page and Schroeder model is used as a foundation but reinterpreted in light of current evidence derived from advanced molecular techniques. The immunological architecture is subsequently dissected through the involvement of its principal cellular players, acting in a dynamic battleground composed of saliva, crevicular fluid, epithelial barriers, and connective tissues. On the frontlines, neutrophils act as double-edged defenders, capable of both microbial clearance and bystander tissue damage. Like macrophages and dendritic cells, they also serve as strategic sensors and shapers of immunity, bridging innate and adaptive responses. Among these, the T cell arsenal includes inflammatory subsets such as Th1, Th17, and cytotoxic cells, balanced by regulatory T cells. B lymphocytes and plasma cells emerge not only as antibody producers but also as pro-inflammatory effectors, with growing evidence implicating autoreactive subsets in tissue damage, particularly in aggressive forms of the disease. Equally critical are the structural cells: gingival fibroblasts, which transition from matrix architects to immune-active contributors under stress, and osteocytes, recognized as mechanosensitive regulators of bone turnover and immune signaling. Alongside osteoblasts and osteoclasts, these elements form a fragile yet responsive osteoimmune axis that determines the trajectory toward either tissue homeostasis or destruction. The molecular arsenal fueling this conflict-cytokines, chemokines, complement, specialized pro-resolving mediators, neuropeptides, and matrix metalloproteinases-is also examined, highlighting how its dysregulation sustains chronic inflammation and drives structural breakdown. The review also explores how this localized immune conflict echoes systemically, contributing to broader immune activation and comorbidity. By reframing periodontitis as a prototypical immune-mediated disease, this work contributes to a deeper understanding of its pathogenesis and provides a framework for future research aimed at disentangling its immunological complexity and clinical heterogeneity for targeted diagnostic strategies and immune-based therapeutics.

Aim: X-linked Hypophosphatemia (XLH), caused by PHEX mutations, hinders skeletal and dental mineralization and contributes to tooth loss. While XLH is associated with dental implant-related complications, no clinical or preclinical studies have investigated socket healing. XLH secondarily disrupts local mineral metabolism by increasing levels of the mineralization inhibitors, osteopontin (OPN) and inorganic pyrophosphate (PP_i). Tissue-nonspecific alkaline phosphatase (TNAP) promotes mineralization by dephosphorylating OPN and hydrolyzing PP_i. In this proof-of-principle study, we hypothesized that alveolar bone socket healing defects in the Hyp mouse model of XLH would be improved by exogenous TNAP.

Methods: Maxillary first molars were extracted from wild-type (WT) and Hyp mice at 6 weeks, and collagen gel ± mineral-targeted TNAP (TNAP-Fc-D₁₀; asfotase alfa) was placed in sockets. Submucosal injections of TNAP-Fc-D₁₀ or saline were delivered at 7 and 14 days post-procedure (dpp) in some mice. Maxillae were collected at 21 dpp for micro-computed tomography, histology, and RT-qPCR.

Results: Untreated Hyp mice showed impaired socket healing compared to WT mice in bone volume and density. TNAP delivered at the time of extraction was unable to improve healing in Hyp mice. However, additional local TNAP delivery increased both alveolar bone volume and density in Hyp mice. Histology indicated repeated TNAP increased both woven and mature bone in Hyp mouse sockets. Immunostaining for osteopontin and bone sialoprotein suggested partial resolution of osteoid accumulation.

Conclusion: TNAP enhanced socket healing in Hyp mice, overcoming inherent bone healing defects in XLH. These results provide new insights into bone healing with implications beyond alveolar bone in XLH.

Periodontitis is a multifactorial inflammatory disease, traditionally attributed to a bacterial biofilm. Increasing evidence indicates that viruses, especially members of the Herpesviridae family, are frequently detected in periodontal lesions and may influence disease onset and progression. This review provides an overview of viruses present in the oral cavity, including Herpesviridae, Papillomaviridae, Retroviridae, SARS-CoV-2, and emerging viral taxa such as Redondoviridae and bacteriophages, and summarizes their reported associations with periodontitis. Proposed mechanisms of viral contribution include modulation of local immune responses, facilitation of bacterial overgrowth, direct cytopathic effects on periodontal tissues, and synergistic interactions with classical periodontal pathobionts. Clinical correlations link viral load and co-infections with increased disease severity. Identification of direct causal relationships and therapeutic aspects, such as antiviral and combined antimicrobial approaches, is the subject of current research; however, clinical evidence remains limited. Overall, specific viruses show direct influence on periodontal bacterial pathogens and affect the host immune response, warranting further longitudinal and functional studies to clarify their exact role in periodontitis onset, progression, and treatment.