Journal of periodontal research最新文献

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.

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.

Aim: To investigate the contribution of the Single Immunoglobulin Interleukin-1 Receptor-Related Molecule (SIGIRR), a recently described negative mediator of inflammation signaling, in experimental periodontitis pathogenesis.

Methods: A comprehensive approach was employed, including the analysis of human periodontal tissues, in vitro experiments with Periodontal ligament stem cells (PDLSCs), and validation in a rat experimental periodontitis model. The mechanistic link between LPS stimulation and SIGIRR downregulation was investigated, focusing on the p38 pathway and transcription factor Sp1. Functional effects of SIGIRR overexpression on inflammatory cytokine production were assessed.

Results: SIGIRR expression was markedly downregulated in periodontitis and LPS-stimulated PDLSCs. This downregulation was mechanistically linked to LPS activation of the p38 pathway, which impaired nuclear translocation of the transcription factor Sp1, a key positive regulator of SIGIRR transcription. SIGIRR overexpression in PDLSCs significantly attenuated LPS-induced production of pro-inflammatory cytokines (IL-6, IL-8, TNF-α). Local administration of a SIGIRR-overexpressing lentivirus in the rat experimental periodontitis model effectively reduced local pro-inflammatory cytokine levels, and promoted alveolar bone repair.

Conclusion: Together, our findings establish a unique role for p38-Sp1-SIGIRR axis in the pathogenesis of experimental periodontitis and provide evidence that SIGIRR gene therapy promises to offer an alternative option for inflammation blockade and bone repair, facilitating the development of a novel therapeutic strategy.

Aim: To identify and validate druggable gene targets for periodontitis using integrative human genomic analyses and to explore their therapeutic potential through pharmacological evaluation.

Methods: To identify therapeutic targets for periodontitis, we performed Mendelian randomization (MR) and colocalization analyses using the cis-expression quantitative trait loci (cis-eQTL) data of druggable genes and genome-wide association studies (GWAS) data. This approach allowed us to pinpoint druggable gene targets significantly associated with periodontitis, which were then validated by immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Next, we applied drug prediction and molecular docking to identify candidate drugs for the key druggable target. Finally, pharmacological analyses were conducted to evaluate the efficacy of these drugs in vitro and in vivo.

Results: A total of six genes (CACNB4, PSMA4, GAA, FGF2, AURKAIP1, and ADAM12) were found to be causally associated with periodontitis in the MR analysis, of which two (CACNB4 and PSMA4) were further supported by colocalization analyses. CACNB4 was significant in both cohorts in MR analysis and supported by localization and experimental evidence. Moreover, the reliability of this target was confirmed in patient samples. We then identified drugs with repurposing potential that target CACNB4, namely verapamil and safinamide. Pharmacological analyses showed that both agents attenuated osteoclast differentiation, indicating therapeutic potential. Importantly, validation at the cellular level confirmed the activity of these candidate drug targets.

Conclusion: Through MR analysis, we identified CACNB4 as a potential druggable gene for periodontitis. Among the drugs targeting CACNB4, verapamil and safinamide emerged as the most promising candidates for periodontitis treatment. Pharmacological studies further demonstrated that these agents may inhibit osteoclast differentiation by targeting CACNB4, thereby offering potential therapeutic options for periodontitis.