Journal of periodontal research最新文献

The periodontium is a uniquely dynamic tissue system requiring precise signaling for lifelong adaptation. The canonical Wnt/β-catenin pathway is a master regulator of bone homeostasis; however, its role in the specialized environment of the alveolar bone-marked by rapid turnover, complex mechanical forces, and exposure to the oral microbiome-remains incompletely understood, particularly in the context of aging. This review critically synthesizes evidence on Wnt signaling in alveolar bone remodeling, with a focus on age-related dysregulation, contrasting established paradigms from long bone biology with emerging oral-tissue-specific data. Wnt/β-catenin signaling is essential for periodontal homeostasis, orchestrating osteoblastogenesis and mechanotransduction. Its activity is compartment-specific within the periodontium and is potently suppressed in pathology. Key mechanisms of age-related decline include the upregulation of Wnt antagonists (e.g., sclerostin, DKK1), cellular senescence, altered FoxO-Wnt crosstalk under oxidative stress, and impaired mechanosensing. These changes converge to disrupt regenerative capacity, tipping the balance toward net alveolar bone loss. Therapeutically, sclerostin inhibition demonstrates robust preclinical efficacy in rescuing bone loss in models of periodontitis and estrogen deficiency. However, the potential cardiovascular risks of systemic Wnt activation suggest that redirecting efforts toward localized delivery strategies could be a promising alternative. Aging induces a multifaceted suppression of regenerative Wnt signaling in the periodontium. Modulating the Wnt pathway shows great potential for oral bone regeneration. However, significant challenges exist, especially in designing local delivery systems that are both safe and effective. Overcoming these hurdles is crucial for successful clinical applications. Future research must bridge the gap between skeletal biology and direct oral-specific investigations to enable targeted therapies that preserve periodontal health in an aging population.

Grade C molar-incisor pattern periodontitis (C-MIP) is the latest in a series of names given to a unique phenotype, characterized by an aggressive and rapid loss of tooth-supporting structures, starting early in life and usually affecting first molars and incisors. Although much less prevalent than the more generalized "chronic" forms of this disease in adults, it affects mostly young individuals of lower socioeconomic status and African descent, or from mixed-race populations, and shows a strong familial aggregation, pointing to a possible genetic contribution, yet not fully elucidated. Even though most of the studies report this disease in adolescents/young adults, it can also be diagnosed in the primary dentition, frequently in the first molar. Thus, proper periodontal examination and radiographs in children are crucial for early diagnosis and treatment. The rapid periodontal breakdown in this disease is also associated with specific microorganisms and a dysfunctional inflammatory response of the host. A. actinomycetemcomitans has been strongly implicated in C-MIP severity and progression, although newer technologies have pointed to the influence of other associated species implicated in this disease in different populations. Additionally, a pro-inflammatory profile along with hypo/hyperactivity of the cellular innate response has been observed in C-MIP. Genetic studies have supported evidence of family aggregation, although specific genes are yet to be identified. Several clinical therapies have been proposed to treat C-MIP over time, and non-surgical periodontal therapy with adjunctive systemic antibiotics has shown a favorable impact on clinical, immunological, and microbiological outcomes in the short and long term in both primary and permanent dentition. This paper aims to review this unique disease, its proposed pathogenic mechanisms, risk factors, treatment outcomes, and the remaining gaps that still require investigation.

Aim: This study evaluated the potential of a beta-defensin-3 mimetic peptide (BDMP), a synthetic cell-penetrating peptide with antimicrobial and immunomodulatory properties, as an adjunctive therapeutic approach for periodontitis.

Methods: BDMP was formulated in a hydroxyethyl cellulose (HEC) gel and assessed for binding affinity, release kinetics, and ability to penetrate cells and gingival tissues. Anti-inflammatory and osteoclast-related signaling pathways were examined in vitro using RAW264.7 macrophages stimulated with lipopolysaccharide (LPS). Effects on osteogenic recovery were evaluated in periodontal ligament stem cells (PDLSCs) under inflammatory conditions. Antimicrobial activity against multispecies biofilms was analyzed by confocal microscopy. In a ligature-induced experimental periodontitis model in beagle dogs, BDMP gel was compared with a subgingival instrumentation (SI)-only (standard-of-care) control, and minocycline gel was included as an active adjunctive comparator. Clinical parameters, inflammatory markers, microbial load, radiographs, micro-CT images, and histology were evaluated.

Results: In vitro, BDMP reduced histone deacetylase 5 (HDAC5) phosphorylation and attenuated downstream NF-κB-associated inflammatory signaling without altering upstream kinase activity. BDMP decreased osteoclast differentiation, reduced inflammatory cytokine transcription, and partially restored osteogenic capacity in LPS-stimulated PDLSCs. BDMP also demonstrated broad-spectrum antimicrobial activity and disrupted mature multispecies biofilms. In vivo, BDMP resulted in greater reductions in gingival inflammation, bleeding, IL-1β levels, and oral spirochetes over 12 weeks compared with the SI-only control. Radiographic images provided qualitative support for reduced bone loss, which was corroborated by micro-CT and histology, indicating attenuation of alveolar bone resorption. When compared with the combination of SI and minocycline arm, BDMP showed comparable or greater improvements in several inflammatory and microbiological parameters.

Conclusion: BDMP exhibited sustained antimicrobial and anti-inflammatory activity and attenuated bone loss in a beagle periodontitis model when used alongside standard SI therapy. These findings support BDMP as a promising adjunctive therapeutic candidate for managing periodontal inflammation and biofilm-associated disease, although further studies are needed to confirm long-term safety and to define its mechanistic contributions to periodontal tissue preservation.

Oral tissue regeneration involves the orchestration of known physiologic wound healing processes to synthesize single or composite tissues with functional, anatomical interfaces. Fundamental to oral tissue regeneration are the four main stages of wound healing: hemostasis, inflammation, proliferation, and remodeling. The oral cavity presents distinct challenges for regeneration due to its highly dynamic environment characterized by mechanical, microbiological, immunological, cellular, and biochemical factors that regulate cell-matrix interactions. The incorporation of natural or synthetic matrices and biologic agents introduces additional considerations in regenerative therapy. The intrinsic capacity for regeneration in oral tissues is dictated by the tissue type and the defect characteristics. Accordingly, defect classification systems aid in treatment planning, guiding the selection of clinical techniques and regenerative biomaterials. This review outlines the fundamental biological principles required to predictably regenerate alveolar bone, gingiva, and the periodontium. Further, emerging technologies poised to advance personalized therapy will be explored, including customized, bioprinted scaffolds, immunoengineering strategies, and organ-on-chip platforms for disease modeling and therapeutic development.

Aims: This study investigated the role of superoxide dismutase 3 (SOD3) in alveolar bone remodeling and cementum repair under orthodontic loading.

Methods: Mice were subjected to models of tooth movement with or without adenovirus-SOD3 treatment, and were examined for osteolytic activity, distance of tooth movement, and volume of root resorption. The periodontal ligament cells (PDLCs) were cultured under mechanical loading or unloaded controls, in the presence or absence of piezo-type mechanosensitive ion channel component1 (Piezo1) inhibitor GsMTx4 or Yes-associated protein (YAP) inhibitor Verteporfin, and were examined for SOD3 expressions. The MC3T3-E1, BMSCs, OCCM-30, BMMs, and RAW264.7 cell cultures with or without recombinant mouse SOD3 (rmSOD3) administration were examined for osteogenic or osteoclastogenic markers.

Results: Orthodontic loading induced SOD3 expressions in the periodontal ligament (PDL). The mechanical force-induced production of SOD3 in the PDLCs was potentially mediated by Piezo1 and YAP signaling. Exogenous rmSOD3 promoted osteoblastogenesis, boosted cementoblast differentiation and mineralization, and inhibited osteoclastogenesis from osteoclast precursors. Adenovirus-mediated SOD3 overexpression in the PDL suppressed osteoclast differentiation, reduced root resorption, and retarded orthodontic tooth movement.

Conclusion: Piezo1-mediated production of SOD3 from the PDLCs protected the root from resorption and retarded tooth movement by suppressing osteoclastogenesis and promoting osteoblast and cementoblast differentiation.

This study elucidates a potential mechanistic pathway by which DAA attenuates IL-1β secretion in HGF-1 cells, through the disruption of NLRP3 inflammasome assembly, thereby highlighting a novel anti-inflammatory property of DAA at the molecular level.

Our study aims to profile EV subtypes and cytokines (IL-4, IL-10, IL-1β, TNF-α) across (1) shallow pockets (≤ 3 mm) in healthy, gingivitis, and periodontitis patients, and (2) deep pockets (≥ 6 mm) in periodontitis patients before and 1 month after NSPT. Preliminary data suggest that sEV-IL-4 and CD9⁺ sEV may reflect treatment response in periodontitis, being elevated in responding versus nonresponding sites.

Periodontal and craniofacial tissue defects are complex regenerative targets as the reconstitution of tissue heterogeneity, interconnection and function is essential for favorable clinical outcomes. Periodontal tissues are additionally challenged by the bacterial and immunological factors associated with oral regeneration. Hydrogels are extracellular matrix-like hydrated polymer networks that represent a diverse class of regenerative materials. Current applications of hydrogels for periodontal and craniofacial tissue regeneration include either independent or combined approaches including serving as scaffolds to support cell migration, proliferation, differentiation and matrix deposition at the defective site, and/or the delivery of biomolecular therapies. The aim of this review is to highlight and classify the hydrogel strategies currently used in the clinical area for the regeneration of periodontal and craniofacial tissues. In addition, we provide a perspective on emerging hydrogel technologies and regenerative strategies under development that may be utilized to address unmet clinical needs.

Periodontitis is a chronic, host-mediated inflammatory disease in which microbial dysbiosis and dysregulated immune responses drive the destruction of tooth-supporting tissues. Although conventional therapy remains centered on mechanical biofilm control, persistent inflammation and alveolar bone loss in susceptible individuals underscore the need for adjunctive strategies. Translating preclinical discoveries into predictable clinical outcomes, however, remains a major challenge in periodontal research. This narrative review integrates two interrelated themes, translational research methodology and adjunctive therapeutic innovation, to critically examine how preclinical findings can be more effectively bridged to clinical practice in periodontitis management. Evidence was synthesized from experimental, translational, and clinical studies retrieved from PubMed, Scopus, and Web of Science up to September 2025. Emphasis was placed on mechanistic insights, model validity, and translational feasibility across host-modulatory, natural, probiotic, and device-based adjuncts. Animal models remain indispensable for mechanistic understanding and therapeutic testing but face biological and methodological limitations that hinder direct extrapolation to humans. Interspecies differences, short disease kinetics, and non-standardized endpoints constrain translational predictability. Addressing these gaps requires refined modeling, standardized outcomes, and integration of systemic risk factors. Within this methodological framework, several adjunctive modalities, including specialized pro-resolving mediators, probiotics, natural compounds such as curcumin and resveratrol, and device-based therapies like antimicrobial photodynamic therapy demonstrate promising anti-inflammatory, osteoimmunomodulatory, and regenerative effects. Emerging translational tools such as bioresponsive drug delivery systems, nanocarriers, 3D-printed scaffolds, and AI-driven precision periodontics may further enhance clinical relevance and patient-specific targeting. Advancing adjunctive periodontal therapy demands harmonized translational models, bioresponsive delivery platforms, and precision diagnostic tools that bridge preclinical efficacy with real-world outcomes. By aligning methodological rigor with therapeutic innovation, translational research can accelerate the safe and effective clinical integration of next-generation adjunctive treatments in periodontitis.

Matrix metalloproteinases (MMPs) represent a family of 23 zinc-dependent endopeptidases central to extracellular matrix remodeling in periodontal and peri-implant diseases. This comprehensive review examines the pathogenic mechanisms, diagnostic applications, and therapeutic targeting potential of the entire MMP family in periodontitis and peri-implantitis. All MMP subfamilies, collagenases (MMP-1, -8, -13), gelatinases (MMP-2, -9), stromelysins (MMP-3, -10, -11), matrilysins (MMP-7, -26), membrane-type MMPs (MT1-6), and others, demonstrate distinct expression patterns and substrate specificities in diseased tissues. MMP-8 and MMP-9 emerge as primary biomarkers, showing 5-6-fold elevations in active periodontitis compared to health, with corresponding increases in activation ratios and decreases in tissue inhibitor of metalloproteinase (TIMP) levels. Diagnostic applications reveal point-of-care active MMP-8 (aMMP-8) immunotests achieve 70%-85% sensitivity and 65%-80% specificity for periodontitis detection, though standardization challenges limit clinical implementation. Salivary and gingival crevicular fluid MMP profiling demonstrates disease-specific signatures, with MMP-8/TIMP-1 ratios serving as progression indicators. Therapeutically, MMP modulation strategies include FDA-approved subantimicrobial dose doxycycline (SDD), which achieves a 40%-60% reduction in clinical attachment loss. Novel approaches encompass selective MMP inhibitors, pro-resolving mediators, and host-modulation therapies, with emerging AI-assisted personalized treatment protocols showing promise. Critically, peri-implantitis exhibits more severe MMP dysregulation than periodontitis, with MMP: TIMP ratios reaching 50:1 versus 20:1, accelerated bone loss patterns, and distinct MT-MMP involvement reflecting titanium surface interactions. Translation barriers include the need for biomarker standardization, the complexity of MMP redundancy, and the requirement for personalized diagnostic thresholds. Future directions emphasize integrating MMP signatures with multi-omics approaches, developing selective inhibitors, and establishing evidence-based clinical guidelines for MMP-targeted precision periodontal medicine.