Aim To identify novel non‐syndromic hereditary gingival fibromatosis (nsHGF)–associated pathogenic variants and discover therapeutic targets for innovative, minimally invasive therapies. Materials and Methods Whole‐genome sequencing was performed to identify the pathogenic variant in a family with nsHGF. Levels of fibrosis markers and the yes‐associated protein/transcriptional coactivator with PDZ‐binding motif (YAP/TAZ) in gingival fibroblasts were measured by qPCR, western blot and immunofluorescence. Conditioned medium from gingival fibroblasts was used to treat THP‐1‐derived macrophages. In vivo pro‐fibrotic behaviour of CHYMASE ‐silenced gingival fibroblasts and verteporfin‐loaded exosome efficacy were evaluated in NOD/SCID mice. Results We identified a novel CHYMASE ( CMA1 ) nonsense mutation (c.114C>A, p.Tyr38*) in the nsHGF family. This mutation caused chymase deficiency in the patient's gingival fibroblasts, directly leading to extracellular matrix (ECM) overproduction through YAP/TAZ activation. Moreover, CHYMASE ‐silenced gingival fibroblasts promoted interleukin‐6 (IL‐6) secretion by macrophages, thereby amplifying pro‐fibrotic responses in gingival fibroblasts. The YAP inhibitor verteporfin suppressed ECM overproduction in CHYMASE ‐silenced gingival fibroblasts. In vivo, topical administration of verteporfin‐loaded exosomes significantly attenuated chymase deficiency–induced fibrosis. Conclusion Our findings support the pathogenic role of the CHYMASE mutation in nsHGF, establish chymase deficiency and consequent YAP/TAZ activation as the underlying mechanism and propose verteporfin‐loaded exosomes as a promising therapeutic strategy for nsHGF‐associated gingival overgrowth.
目的发现新的非综合征性遗传性牙龈纤维瘤病（nsHGF）相关的致病变异，并发现创新的微创治疗靶点。材料和方法采用全基因组测序方法鉴定一个nsHGF家族的致病变异。通过qPCR、western blot和免疫荧光检测牙龈成纤维细胞中纤维化标志物和yes相关蛋白/带PDZ结合基序的转录共激活因子（YAP/TAZ）的水平。使用牙龈成纤维细胞的条件培养基处理THP‐1来源的巨噬细胞。在NOD/SCID小鼠中评估了CHYMASE沉默的牙龈成纤维细胞的体内促纤维化行为和载维替porfin的外泌体功效。结果在nsHGF家族中发现了一个新的CHYMASE （CMA1）无义突变（c.114C> a, p.Tyr38*）。这种突变导致患者的牙龈成纤维细胞中乳糜酶缺乏，通过YAP/TAZ激活直接导致细胞外基质（ECM）过量产生。此外，CHYMASE沉默的牙龈成纤维细胞促进巨噬细胞分泌白细胞介素- 6 (IL - 6)，从而增强了牙龈成纤维细胞的促纤维化反应。YAP抑制剂维替波芬抑制CHYMASE沉默的牙龈成纤维细胞中ECM的过量产生。在体内，局部施用载维替波芬的外泌体可显著减轻乳糜酶缺乏症引起的纤维化。结论我们的研究结果支持了CHYMASE突变在nsHGF中的致病作用，确定了CHYMASE缺陷和随后的YAP/TAZ激活是潜在的机制，并提出了满载维替波芬的外泌体作为治疗nsHGF相关牙龈过度生长的有希望的治疗策略。
{"title":"Non‐Syndromic Hereditary Gingival Fibromatosis Driven by Chymase Deficiency Is Attenuated by Verteporfin‐Loaded Exosomes","authors":"Xin Chen, Yuqing Guo, Yangqiao Qing, Runze Li, Haotian Luo, Hio Cheng Ieong, Bingyan Guo, Zichun Huang, Yungshan Teng, Ruoyu Li, Wenfeng Li, Danying Chen, Yang Cao, Weicai Wang, Chen Zhou","doi":"10.1111/jcpe.70077","DOIUrl":"https://doi.org/10.1111/jcpe.70077","url":null,"abstract":"Aim To identify novel non‐syndromic hereditary gingival fibromatosis (nsHGF)–associated pathogenic variants and discover therapeutic targets for innovative, minimally invasive therapies. Materials and Methods Whole‐genome sequencing was performed to identify the pathogenic variant in a family with nsHGF. Levels of fibrosis markers and the yes‐associated protein/transcriptional coactivator with PDZ‐binding motif (YAP/TAZ) in gingival fibroblasts were measured by qPCR, western blot and immunofluorescence. Conditioned medium from gingival fibroblasts was used to treat THP‐1‐derived macrophages. In vivo pro‐fibrotic behaviour of <jats:italic>CHYMASE</jats:italic> ‐silenced gingival fibroblasts and verteporfin‐loaded exosome efficacy were evaluated in NOD/SCID mice. Results We identified a novel <jats:italic>CHYMASE</jats:italic> ( <jats:italic>CMA1</jats:italic> ) nonsense mutation (c.114C>A, p.Tyr38*) in the nsHGF family. This mutation caused chymase deficiency in the patient's gingival fibroblasts, directly leading to extracellular matrix (ECM) overproduction through YAP/TAZ activation. Moreover, <jats:italic>CHYMASE</jats:italic> ‐silenced gingival fibroblasts promoted interleukin‐6 (IL‐6) secretion by macrophages, thereby amplifying pro‐fibrotic responses in gingival fibroblasts. The YAP inhibitor verteporfin suppressed ECM overproduction in <jats:italic>CHYMASE</jats:italic> ‐silenced gingival fibroblasts. In vivo, topical administration of verteporfin‐loaded exosomes significantly attenuated chymase deficiency–induced fibrosis. Conclusion Our findings support the pathogenic role of the <jats:italic>CHYMASE</jats:italic> mutation in nsHGF, establish chymase deficiency and consequent YAP/TAZ activation as the underlying mechanism and propose verteporfin‐loaded exosomes as a promising therapeutic strategy for nsHGF‐associated gingival overgrowth.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"39 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMPregnancy gingivitis is potentially modifiable, making it a promising target for preventive strategies to reduce adverse obstetrical outcomes. The primary objective of this study was to evaluate whether an interdental hygiene intervention in early pregnancy could reduce obstetrical complications. Exploratory analyses focused on potential biological pathways linking oral inflammation and obstetrical outcomes.MATERIALS AND METHODSA two-arm randomised controlled trial (RCT) with cluster allocation (1:1) was conducted in six antenatal clinics in Senegal among nulliparous women at 12 weeks. Participants received either a daily calibrated interdental brushing intervention (Intervention) or usual oral hygiene (Control). Follow-up visits were scheduled at 5 and 8 months. The primary endpoint was a composite of preterm birth, low birth weight, small for gestational age or pre-eclampsia, analysed exploratorily under the intention-to-treat principle.RESULTSA total of 323 women were randomised (162 intervention, 161 control). The composite outcome occurred in 28.4% of the intervention group and 24.2% of the control group (p = 0.449). After adjustment, the intervention was not significantly associated (aOR = 0.65; 95% CI: 0.39-1.10; p = 0.107). Exploratory analyses suggested that interdental bleeding and C-reactive protein (CRP) could act as mediators, accounting for ~60% of the effect, with the remaining ~40% representing a direct effect. No intervention-related adverse events were observed.CONCLUSIONThis RCT did not demonstrate a significant reduction in obstetrical complications with early interdental prophylaxis. However, the intervention was safe, acceptable and feasible within antenatal care, highlighting the need for adequately powered trials to clarify its potential clinical impact.
{"title":"Interdental Brushing and Obstetrical Outcomes in Nulliparous Pregnant Women: Insights From a Cluster Randomised Controlled Trial.","authors":"Denis Bourgeois,Aida Kanoute,Daouda Faye,Marta Mazur,Hervé Perrier,Roman Ardan,Céline Clément,Lucio Souza Gonçalves,Romain Lan,Florence Carrouel","doi":"10.1111/jcpe.70070","DOIUrl":"https://doi.org/10.1111/jcpe.70070","url":null,"abstract":"AIMPregnancy gingivitis is potentially modifiable, making it a promising target for preventive strategies to reduce adverse obstetrical outcomes. The primary objective of this study was to evaluate whether an interdental hygiene intervention in early pregnancy could reduce obstetrical complications. Exploratory analyses focused on potential biological pathways linking oral inflammation and obstetrical outcomes.MATERIALS AND METHODSA two-arm randomised controlled trial (RCT) with cluster allocation (1:1) was conducted in six antenatal clinics in Senegal among nulliparous women at 12 weeks. Participants received either a daily calibrated interdental brushing intervention (Intervention) or usual oral hygiene (Control). Follow-up visits were scheduled at 5 and 8 months. The primary endpoint was a composite of preterm birth, low birth weight, small for gestational age or pre-eclampsia, analysed exploratorily under the intention-to-treat principle.RESULTSA total of 323 women were randomised (162 intervention, 161 control). The composite outcome occurred in 28.4% of the intervention group and 24.2% of the control group (p = 0.449). After adjustment, the intervention was not significantly associated (aOR = 0.65; 95% CI: 0.39-1.10; p = 0.107). Exploratory analyses suggested that interdental bleeding and C-reactive protein (CRP) could act as mediators, accounting for ~60% of the effect, with the remaining ~40% representing a direct effect. No intervention-related adverse events were observed.CONCLUSIONThis RCT did not demonstrate a significant reduction in obstetrical complications with early interdental prophylaxis. However, the intervention was safe, acceptable and feasible within antenatal care, highlighting the need for adequately powered trials to clarify its potential clinical impact.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"36 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim To identify shared genetic architectures and molecular pathways underlying the frequent co‐occurrence of stage III/IV grade C periodontitis under 35 years of age (PIII/IV‐C< 35y) and abnormal root morphology (ARM), using a family‐based SNP set and transcriptomic approach. Materials and Methods We conducted a family‐based study using whole‐genome genotyping of 148 Han Chinese individuals from 52 families, including 52 probands, 35 mothers, 32 fathers and 29 siblings. The participants included 65 comorbidity cases, 29 PIII/IV‐C< 35y‐only cases, 27 ARM‐only cases and 27 controls. Whole‐genome genotyping and bi‐clustering were used to identify SNP sets associated with each phenotype, and transcriptomic profiling was performed to validate gene expression changes. Results Among 109 SNP sets, 91 (83.5%) showed ≥ 40% comorbidity risk. Fifty‐four and 27 SNP sets were significantly associated with PIII/IV‐C< 35y and ARM, respectively. Six genotype subnetworks were enriched for neural development and inflammation pathways, particularly IL‐17 signalling. Transcriptome data confirmed down‐regulation of KLHL29 , HSF2 and COL13A1 in PIII/IV‐C< 35y, and a reduction in GJA1 expression in comorbidity cases. Conclusions This study reveals a shared genetic architecture between PIII/IV‐C< 35y and ARM, implicating neural development and inflammatory pathways in their co‐occurrence. Key genes such as GJA1 may advance mechanistic understanding and support early identification of high‐risk individuals.
{"title":"Shared Genotypic Architectures of Stage III / IV Grade C Periodontitis Under 35 Years of Age (Former Aggressive Periodontitis) and Abnormal Root Morphology: A Family‐Based Study","authors":"Xiaoyuan Guan, Xiaoyi Li, Dafang Chen, Li Xu, Wenjing Li, Ruifang Lu, Xian'e Wang, Huanxin Meng","doi":"10.1111/jcpe.70071","DOIUrl":"https://doi.org/10.1111/jcpe.70071","url":null,"abstract":"Aim To identify shared genetic architectures and molecular pathways underlying the frequent co‐occurrence of stage III/IV grade C periodontitis under 35 years of age (PIII/IV‐C< 35y) and abnormal root morphology (ARM), using a family‐based SNP set and transcriptomic approach. Materials and Methods We conducted a family‐based study using whole‐genome genotyping of 148 Han Chinese individuals from 52 families, including 52 probands, 35 mothers, 32 fathers and 29 siblings. The participants included 65 comorbidity cases, 29 PIII/IV‐C< 35y‐only cases, 27 ARM‐only cases and 27 controls. Whole‐genome genotyping and bi‐clustering were used to identify SNP sets associated with each phenotype, and transcriptomic profiling was performed to validate gene expression changes. Results Among 109 SNP sets, 91 (83.5%) showed ≥ 40% comorbidity risk. Fifty‐four and 27 SNP sets were significantly associated with PIII/IV‐C< 35y and ARM, respectively. Six genotype subnetworks were enriched for neural development and inflammation pathways, particularly IL‐17 signalling. Transcriptome data confirmed down‐regulation of <jats:italic>KLHL29</jats:italic> , <jats:italic>HSF2</jats:italic> and <jats:italic>COL13A1</jats:italic> in PIII/IV‐C< 35y, and a reduction in <jats:italic>GJA1</jats:italic> expression in comorbidity cases. Conclusions This study reveals a shared genetic architecture between PIII/IV‐C< 35y and ARM, implicating neural development and inflammatory pathways in their co‐occurrence. Key genes such as <jats:italic>GJA1</jats:italic> may advance mechanistic understanding and support early identification of high‐risk individuals.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"27 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Niu, Xiaojing Ke, Wei Zhou, Baochun Tan, Junjie Zhao, Bin Chen, Yanfen Li, Peng Zhang, Fuhua Yan, Houxuan Li
Aim To assess a new material in comparison with free gingival graft (FGG) for increasing the width of keratinised tissue (KT). Material and Methods Forty‐six participants were randomly allocated to the absorbable gradient membrane (AGM) or the FGG group. This trial used inter‐patient comparison to establish the non‐inferiority of AGM compared to FGG. The primary outcome (KT) was examined from baseline to 3 years after surgery. Secondary outcomes included the plaque index (PI), bleeding index (BI), gingival recession (GR), probing depth (PD), immunoglobulin E (IgE) level, postoperative pain, aesthetics and patient satisfaction. Results The width of KT in the AGM group was non‐inferior to that of the FGG group at all short‐term follow‐ups (1, 3 and 6 months), with a pre‐defined margin of 1 mm. However, this non‐inferiority disappeared by 3 years after operation. From 6 months to 3 years, the GR associated with FGG significantly decreased, while that associated with AGM showed no significant change between adjacent time points. No significant differences were observed in PI, BI, PD or IgE levels between the groups. AGM required shorter surgery times and secured better aesthetic outcomes than FGG. Conclusion AGM showed short‐term non‐inferiority to FGG for KT augmentation. However, the non‐inferiority was not sustained at 3 years. Trial Registration The study was registered with the China Clinical Trial Center under ChiCTR2000034683. Informed consent was obtained from all participants
{"title":"Clinical Evaluation of Absorbable Gradient Membrane vs. Free Gingival Grafts for Periodontal Soft‐Tissue Augmentation: A Randomised Controlled Clinical Trial","authors":"Li Niu, Xiaojing Ke, Wei Zhou, Baochun Tan, Junjie Zhao, Bin Chen, Yanfen Li, Peng Zhang, Fuhua Yan, Houxuan Li","doi":"10.1111/jcpe.70073","DOIUrl":"https://doi.org/10.1111/jcpe.70073","url":null,"abstract":"Aim To assess a new material in comparison with free gingival graft (FGG) for increasing the width of keratinised tissue (KT). Material and Methods Forty‐six participants were randomly allocated to the absorbable gradient membrane (AGM) or the FGG group. This trial used inter‐patient comparison to establish the non‐inferiority of AGM compared to FGG. The primary outcome (KT) was examined from baseline to 3 years after surgery. Secondary outcomes included the plaque index (PI), bleeding index (BI), gingival recession (GR), probing depth (PD), immunoglobulin E (IgE) level, postoperative pain, aesthetics and patient satisfaction. Results The width of KT in the AGM group was non‐inferior to that of the FGG group at all short‐term follow‐ups (1, 3 and 6 months), with a pre‐defined margin of 1 mm. However, this non‐inferiority disappeared by 3 years after operation. From 6 months to 3 years, the GR associated with FGG significantly decreased, while that associated with AGM showed no significant change between adjacent time points. No significant differences were observed in PI, BI, PD or IgE levels between the groups. AGM required shorter surgery times and secured better aesthetic outcomes than FGG. Conclusion AGM showed short‐term non‐inferiority to FGG for KT augmentation. However, the non‐inferiority was not sustained at 3 years. Trial Registration The study was registered with the China Clinical Trial Center under ChiCTR2000034683. Informed consent was obtained from all participants","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"372 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim To compare acute‐phase response and blood pressure levels following full‐mouth or quadrant non‐surgical periodontal treatment (FM‐SRP or Q‐SRP) in patients affected by hypertension and periodontitis. Patients and Methods Forty patients affected by hypertension and periodontitis were enrolled and randomly allocated to either the FM‐SRP or Q‐SRP group. Periodontal parameters were registered at baseline and 3 months after treatment. Blood samples and vital signs were collected at baseline, 24 h and 3 months after treatment. Primary outcomes were high‐sensitivity C‐reactive protein (hs‐CRP) concentration 24 h post operation and the variation in levels of blood pressure (BP). Results Significant increase in hs‐CRP levels was observed at 24 h, with FM‐SRP presenting higher values than Q‐SRP ( p < 0.05). In terms of periodontal outcomes, both treatment regimens proved equally effective. Systolic BP was significantly reduced at days 1 and 90 in both groups ( p < 0.01), while a 90‐day significant decrease in diastolic BP was detected only in the Q‐SRP group ( p < 0.01). Multiple regression analysis suggests that the peak of hs‐CRP at 24 h may influence BP reduction at Day 90. Conclusions Q‐SRP may be preferred in patients affected by hypertension and periodontitis, as a higher post‐operative inflammatory response was associated with lower improvements in BP control in the medium term.
{"title":"Acute‐Phase Response Following Different Modalities of Non‐Surgical Periodontal Treatment in Subjects Affected by Periodontitis and Co‐Morbid Hypertension: A Randomised Clinical Trial","authors":"Morena Petrini, Stefano Gennai, Crystal Marruganti, Urska Marhl, Rossana Izzetti, Marco Nisi, Filippo Graziani","doi":"10.1111/jcpe.70068","DOIUrl":"https://doi.org/10.1111/jcpe.70068","url":null,"abstract":"Aim To compare acute‐phase response and blood pressure levels following full‐mouth or quadrant non‐surgical periodontal treatment (FM‐SRP or Q‐SRP) in patients affected by hypertension and periodontitis. Patients and Methods Forty patients affected by hypertension and periodontitis were enrolled and randomly allocated to either the FM‐SRP or Q‐SRP group. Periodontal parameters were registered at baseline and 3 months after treatment. Blood samples and vital signs were collected at baseline, 24 h and 3 months after treatment. Primary outcomes were high‐sensitivity C‐reactive protein (hs‐CRP) concentration 24 h post operation and the variation in levels of blood pressure (BP). Results Significant increase in hs‐CRP levels was observed at 24 h, with FM‐SRP presenting higher values than Q‐SRP ( <jats:italic>p</jats:italic> < 0.05). In terms of periodontal outcomes, both treatment regimens proved equally effective. Systolic BP was significantly reduced at days 1 and 90 in both groups ( <jats:italic>p</jats:italic> < 0.01), while a 90‐day significant decrease in diastolic BP was detected only in the Q‐SRP group ( <jats:italic>p</jats:italic> < 0.01). Multiple regression analysis suggests that the peak of hs‐CRP at 24 h may influence BP reduction at Day 90. Conclusions Q‐SRP may be preferred in patients affected by hypertension and periodontitis, as a higher post‐operative inflammatory response was associated with lower improvements in BP control in the medium term.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"28 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabel Lopez-Oliva,Iain L Chapple,Akshay Paropkari,Shweta Saraswat,Praveen Sharma,Stefan Serban,Paola de Pablo,Karim Raza,Andrew Filer,Thomas Dietrich,Melissa Grant,Purnima S Kumar
AIMTo explore mechanistic links between rheumatoid arthritis (RA) and periodontitis (PD) through the lens of subgingival microbial dysbiosis-mediated inflammation.METHODSSubgingival plaque from 100 volunteers with RA and PD (RAPD), 22 with RA (RAnoPD), 18 with PD (PDnoRA) and 19 healthy controls (noRAnoPD) was analysed using 16S-amplicon sequencing, semi-quantitative bead-based flow cytometry to measure crevicular fluid cytokines and ELISA to quantify antibodies to oral pathogens and systemic inflammatory markers in serum. The RAPD group had been randomised to receive intensive non-surgical periodontal therapy (PMPR) or oral hygiene alone and reviewed at 3 and 6 months in our previously reported study.RESULTSSubgingival microbial dysbiosis, as evidenced by higher species richness, alpha-diversity and higher levels of known and putative periodontal pathobionts, was evident at baseline in RAnoPD, RAPD and PDnoRA. Higher serum antibodies to oral pathogens were recorded in RAPD. PMPR restored host-microbial homeostasis in RAPD within 3 months. Significant decreases in serum antibodies to microbial antigens and clinical measures of RA activity were seen after 3 and 6 months in the PMPR group but not controls.CONCLUSIONSWe demonstrate a mutualistic influence of RA and PD, beginning with RA-induced dysbiosis of the periodontal microbiome, progressing to periodontal inflammation and culminating in PD-driven exacerbation of systemic inflammation.
{"title":"Dysbiosis-Mediated Inflammation: A Pathophysiological Link Between Rheumatoid Arthritis and Periodontitis.","authors":"Isabel Lopez-Oliva,Iain L Chapple,Akshay Paropkari,Shweta Saraswat,Praveen Sharma,Stefan Serban,Paola de Pablo,Karim Raza,Andrew Filer,Thomas Dietrich,Melissa Grant,Purnima S Kumar","doi":"10.1111/jcpe.70063","DOIUrl":"https://doi.org/10.1111/jcpe.70063","url":null,"abstract":"AIMTo explore mechanistic links between rheumatoid arthritis (RA) and periodontitis (PD) through the lens of subgingival microbial dysbiosis-mediated inflammation.METHODSSubgingival plaque from 100 volunteers with RA and PD (RAPD), 22 with RA (RAnoPD), 18 with PD (PDnoRA) and 19 healthy controls (noRAnoPD) was analysed using 16S-amplicon sequencing, semi-quantitative bead-based flow cytometry to measure crevicular fluid cytokines and ELISA to quantify antibodies to oral pathogens and systemic inflammatory markers in serum. The RAPD group had been randomised to receive intensive non-surgical periodontal therapy (PMPR) or oral hygiene alone and reviewed at 3 and 6 months in our previously reported study.RESULTSSubgingival microbial dysbiosis, as evidenced by higher species richness, alpha-diversity and higher levels of known and putative periodontal pathobionts, was evident at baseline in RAnoPD, RAPD and PDnoRA. Higher serum antibodies to oral pathogens were recorded in RAPD. PMPR restored host-microbial homeostasis in RAPD within 3 months. Significant decreases in serum antibodies to microbial antigens and clinical measures of RA activity were seen after 3 and 6 months in the PMPR group but not controls.CONCLUSIONSWe demonstrate a mutualistic influence of RA and PD, beginning with RA-induced dysbiosis of the periodontal microbiome, progressing to periodontal inflammation and culminating in PD-driven exacerbation of systemic inflammation.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"1 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emilio Couso‐Queiruga, Miguel Padial‐Molina, Pablo Galindo‐Moreno, Carlos Garaicoa‐Pazmino, Nicolly Oliveira‐Santos, Giuseppe Troiano, Vivianne Chappuis, Gustavo Avila‐Ortiz
Aim To evaluate the effect of specific phenotypical and anatomical features of the alveolar process and basal bone on post‐extraction dimensional changes. Materials and Methods Patients requiring the extraction of a single maxillary non‐molar tooth were enrolled. A comprehensive panel of baseline anatomical characteristics, including sagittal root position (SRP) class, was recorded. Linear and volumetric bone changes and the need for ancillary bone augmentation (NBA) were assessed after a 14‐week healing period. Results Records from 65 patients were included. Facial bone thickness (FBT) ≤ 1 mm was associated with significantly greater dimensional changes and greater NBA compared to sites presenting FBT > 1 mm (88.46% vs. 35.13%; p < 0.002). Bone remodelling and NBA were highest in SRP Class IV (100%), with lower frequencies in Class I (60%) and Class II (43.5%). Sites with roots outside the bony housing showed significantly more remodelling and NBA (89.47% vs. 43.18%; p < 0.001). Sites with a basal bone width narrower than the alveolar processes exhibited significantly greater bone remodelling and a higher prevalence of NBA compared to sites where the basal bone was wider (88.89% vs. 50%; p = 0.09). Socket entrance dimensions, distance from the coronal aspect of the facial bone to adjacent boundaries and root volume showed a comparable trend towards increased dimensional changes and grafting. Conclusions Certain site‐specific features appear to significantly affect post‐extraction alveolar ridge remodelling and the subsequent NBA to facilitate implant therapy.
目的探讨牙槽突和基底骨的特定表型和解剖特征对拔牙后尺寸变化的影响。材料和方法选择需要拔除单颗上颌非磨牙的患者。全面的基线解剖特征，包括矢状根位置（SRP）分类，被记录。在14周的愈合期后，评估线性和体积骨变化以及辅助骨增强（NBA）的需求。结果纳入65例患者的记录。与面骨厚度≤1 mm的部位相比，面骨厚度≤1 mm的部位有更大的尺寸变化和更大的NBA （88.46% vs. 35.13%; p < 0.002）。骨重塑和NBA在SRP IV类中发生率最高（100%），在I类和II类中发生率较低（60%）（43.5%）。根在骨壳外的部位表现出更多的重塑和NBA （89.47% vs. 43.18%; p < 0.001）。与基底骨较宽的部位相比，基底骨宽度小于牙槽突的部位表现出更大的骨重塑和更高的NBA患病率（88.89%比50%；p = 0.09）。窝口尺寸、从面骨冠状面到相邻边界的距离和根体积都显示出类似的尺寸变化和嫁接增加的趋势。结论：某些特定部位的特征似乎显著影响拔牙后牙槽嵴重塑和随后的NBA，以促进种植治疗。
{"title":"Effect of Alveolar Process and Basal Bone Features on Post‐Extraction Dimensional Changes","authors":"Emilio Couso‐Queiruga, Miguel Padial‐Molina, Pablo Galindo‐Moreno, Carlos Garaicoa‐Pazmino, Nicolly Oliveira‐Santos, Giuseppe Troiano, Vivianne Chappuis, Gustavo Avila‐Ortiz","doi":"10.1111/jcpe.70069","DOIUrl":"https://doi.org/10.1111/jcpe.70069","url":null,"abstract":"Aim To evaluate the effect of specific phenotypical and anatomical features of the alveolar process and basal bone on post‐extraction dimensional changes. Materials and Methods Patients requiring the extraction of a single maxillary non‐molar tooth were enrolled. A comprehensive panel of baseline anatomical characteristics, including sagittal root position (SRP) class, was recorded. Linear and volumetric bone changes and the need for ancillary bone augmentation (NBA) were assessed after a 14‐week healing period. Results Records from 65 patients were included. Facial bone thickness (FBT) ≤ 1 mm was associated with significantly greater dimensional changes and greater NBA compared to sites presenting FBT > 1 mm (88.46% vs. 35.13%; <jats:italic>p</jats:italic> < 0.002). Bone remodelling and NBA were highest in SRP Class IV (100%), with lower frequencies in Class I (60%) and Class II (43.5%). Sites with roots outside the bony housing showed significantly more remodelling and NBA (89.47% vs. 43.18%; <jats:italic>p</jats:italic> < 0.001). Sites with a basal bone width narrower than the alveolar processes exhibited significantly greater bone remodelling and a higher prevalence of NBA compared to sites where the basal bone was wider (88.89% vs. 50%; <jats:italic>p</jats:italic> = 0.09). Socket entrance dimensions, distance from the coronal aspect of the facial bone to adjacent boundaries and root volume showed a comparable trend towards increased dimensional changes and grafting. Conclusions Certain site‐specific features appear to significantly affect post‐extraction alveolar ridge remodelling and the subsequent NBA to facilitate implant therapy.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"50 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jean‐Claude Imber, Andrea Roccuzzo, Nikola Saulacic, Maria Permuy Mendaña, Sıla Cagrı Isler, Dieter D. Bosshardt, Anton Sculean, Alexandra Stähli
Aim To evaluate the regenerative potential of liquid platelet–rich fibrin ( PRF ), with and without a volume‐stable collagen matrix ( VCMX ), in periodontal intrabony defects using histological, histometric and micro‐ CT analyses. Materials and Methods One‐wall intrabony defects were surgically created in six beagle dogs and treated with either VCMX plus liquid PRF (TG1), liquid PRF alone (TG2), VCMX alone (CG1) or left empty (CG2). After 12 weeks, samples were analysed by micro‐CT, histology and histometry. Results Healing was uneventful in all animals. TG1 showed the greatest cementum (4.08 ± 0.88 mm) and bone formation (3.42 ± 0.70 mm), followed by TG2 (2.92 ± 1.13 mm cementum, 3.19 ± 0.78 mm bone) and CG1 (2.07 ± 1.06 mm cementum, 3.29 ± 0.77 mm bone). CG2 exhibited the poorest outcomes (0.84 ± 0.74 mm cementum, 2.58 ± 0.38 mm bone). Micro‐CT confirmed higher bone volume in TG1 and TG2 compared to CG2; however, the difference was not significant. All treatment groups showed significantly greater cementum and bone formation compared to CG2. Conclusions Within its limitations, the present study indicates that (i) liquid PRF, alone or combined with a volume‐stable collagen matrix, enhances periodontal regeneration more than open flap debridement alone, and (ii) the combination tends to show the most favourable outcomes.
目的通过组织学、组织计量学和显微CT分析，评估富血小板液体纤维蛋白（PRF）在有和没有体积稳定的胶原基质（VCMX）情况下修复牙周骨内缺损的再生潜力。材料与方法对6只beagle犬进行骨内单壁缺损手术治疗，分别用VCMX加液体PRF （TG1）、液体PRF单独（TG2）、VCMX单独（CG1）或空置（CG2）治疗。12周后，对样品进行显微CT、组织学和组织计量学分析。结果所有动物均愈合顺利。TG1骨质（4.08±0.88 mm）和骨形成（3.42±0.70 mm）最大，其次为TG2（2.92±1.13 mm, 3.19±0.78 mm）和CG1（2.07±1.06 mm, 3.29±0.77 mm）。CG2表现最差（骨质0.84±0.74 mm，骨2.58±0.38 mm）。微CT证实TG1和TG2骨体积高于CG2；然而，差异并不显著。与CG2相比，所有治疗组的骨质和骨形成均显著增加。在其局限性内，本研究表明：(1)液体PRF单独使用或与体积稳定的胶原基质联合使用，比单独使用开瓣清创更能促进牙周再生，(2)联合使用往往显示出最有利的结果。
{"title":"Preclinical Evaluation of the Effect of Liquid Platelet–Rich Fibrin and a Volume‐Stable Collagen Matrix on Periodontal Regeneration","authors":"Jean‐Claude Imber, Andrea Roccuzzo, Nikola Saulacic, Maria Permuy Mendaña, Sıla Cagrı Isler, Dieter D. Bosshardt, Anton Sculean, Alexandra Stähli","doi":"10.1111/jcpe.70065","DOIUrl":"https://doi.org/10.1111/jcpe.70065","url":null,"abstract":"Aim To evaluate the regenerative potential of liquid platelet–rich fibrin ( <jats:styled-content style=\"fixed-case\">PRF</jats:styled-content> ), with and without a volume‐stable collagen matrix ( <jats:styled-content style=\"fixed-case\">VCMX</jats:styled-content> ), in periodontal intrabony defects using histological, histometric and micro‐ <jats:styled-content style=\"fixed-case\">CT</jats:styled-content> analyses. Materials and Methods One‐wall intrabony defects were surgically created in six beagle dogs and treated with either VCMX plus liquid PRF (TG1), liquid PRF alone (TG2), VCMX alone (CG1) or left empty (CG2). After 12 weeks, samples were analysed by micro‐CT, histology and histometry. Results Healing was uneventful in all animals. TG1 showed the greatest cementum (4.08 ± 0.88 mm) and bone formation (3.42 ± 0.70 mm), followed by TG2 (2.92 ± 1.13 mm cementum, 3.19 ± 0.78 mm bone) and CG1 (2.07 ± 1.06 mm cementum, 3.29 ± 0.77 mm bone). CG2 exhibited the poorest outcomes (0.84 ± 0.74 mm cementum, 2.58 ± 0.38 mm bone). Micro‐CT confirmed higher bone volume in TG1 and TG2 compared to CG2; however, the difference was not significant. All treatment groups showed significantly greater cementum and bone formation compared to CG2. Conclusions Within its limitations, the present study indicates that (i) liquid PRF, alone or combined with a volume‐stable collagen matrix, enhances periodontal regeneration more than open flap debridement alone, and (ii) the combination tends to show the most favourable outcomes.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"15 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuyu Cheng, Shiyuan Song, Wen Zhang, Dan Qiao, Min Wang, Zhifeng Wang, Jiajie Pu, Wenrong Yang, Fuhua Yan, Yangheng Zhang
Aim To investigate the association between tryptophan‐derived microbial metabolites and periodontitis, and to assess whether the differential tryptophan metabolite indole‐3‐acetic acid (IAA) could ameliorate periodontitis and elucidate its potential mechanism. Materials and Methods The association between tryptophan‐derived metabolites and periodontitis was evaluated using targeted metabolomics analysis, 16S rRNA gene amplicon sequencing and correlation analysis. The impact of the differential metabolite IAA on periodontitis was assessed with micro‐computed tomography (micro‐CT), histological staining and real‐time quantitative polymerase chain reaction (RT‐qPCR). The effects of IAA on macrophages under an inflammatory microenvironment, along with its potential mechanism, were explored using RT‐qPCR, enzyme‐linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot. Results IAA, a differential tryptophan metabolite, was identified in the saliva of patients with periodontitis and periodontally healthy individuals. Local application of IAA in experimental mice with periodontitis alleviated the immune‐inflammatory response and reduced periodontal tissue destruction. Mechanistically, IAA induced M2 macrophage polarisation by activating the AhR/CYP1A1 axis, thereby contributing to the amelioration of periodontal destruction. Conclusions These findings highlight the potential role of the microbial metabolite IAA in the development and treatment of periodontitis, offering a new perspective for intervention strategies based on microbial metabolites for periodontitis.
{"title":"Tryptophan‐Derived Microbial Metabolite Indole‐3‐Acetic Acid Ameliorates Periodontitis Through AhR / CYP1A1 ‐Mediated Macrophage Polarisation","authors":"Shuyu Cheng, Shiyuan Song, Wen Zhang, Dan Qiao, Min Wang, Zhifeng Wang, Jiajie Pu, Wenrong Yang, Fuhua Yan, Yangheng Zhang","doi":"10.1111/jcpe.70064","DOIUrl":"https://doi.org/10.1111/jcpe.70064","url":null,"abstract":"Aim To investigate the association between tryptophan‐derived microbial metabolites and periodontitis, and to assess whether the differential tryptophan metabolite indole‐3‐acetic acid (IAA) could ameliorate periodontitis and elucidate its potential mechanism. Materials and Methods The association between tryptophan‐derived metabolites and periodontitis was evaluated using targeted metabolomics analysis, 16S rRNA gene amplicon sequencing and correlation analysis. The impact of the differential metabolite IAA on periodontitis was assessed with micro‐computed tomography (micro‐CT), histological staining and real‐time quantitative polymerase chain reaction (RT‐qPCR). The effects of IAA on macrophages under an inflammatory microenvironment, along with its potential mechanism, were explored using RT‐qPCR, enzyme‐linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot. Results IAA, a differential tryptophan metabolite, was identified in the saliva of patients with periodontitis and periodontally healthy individuals. Local application of IAA in experimental mice with periodontitis alleviated the immune‐inflammatory response and reduced periodontal tissue destruction. Mechanistically, IAA induced M2 macrophage polarisation by activating the AhR/CYP1A1 axis, thereby contributing to the amelioration of periodontal destruction. Conclusions These findings highlight the potential role of the microbial metabolite IAA in the development and treatment of periodontitis, offering a new perspective for intervention strategies based on microbial metabolites for periodontitis.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"88 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Wu, Jiawei Lu, Zehui Xiong, Jie Huang, Jinyi Zhang, Lijun Luo
Aim To investigate the impact of neutrophil extracellular traps (NETs) on periodontitis and the regulatory mechanisms by which melatonin alleviates the disease. Materials and Methods The expression of NET markers in periodontitis tissues was detected using multiple immunohistochemical staining. The effect of NETs on periodontitis was explored through in vivo and in vitro experiments. qPCR and transwell migration assay were used to assess neutrophil activation and recruitment. Flow cytometry, micro‐CT and histological staining were employed to evaluate neutrophil recruitment in gingiva and periodontitis progression in a ligature‐induced periodontitis (LIP) mouse model. Melatonin was then administered in vivo and in vitro to evaluate its effects on NET formation, neutrophil activation, neutrophil recruitment and periodontitis progression. Finally, Western blotting and qPCR were employed to elucidate the mechanisms underlying melatonin‐mediated regulation of NET formation. Results NETs were evident in gingival tissues from patients with periodontitis. After inhibiting NET formation, the expression levels of inflammatory cytokines (Il‐1β, Il‐6, Tnf‐α), neutrophil chemokines (Ccl2, Ccl4, Cxcl1) and neutrophil recruitment were found to decrease. Furthermore, melatonin treatment reduced NET formation, decreased neutrophil activation and recruitment and alleviated bone resorption in LIP mice. Mechanistically, melatonin suppresses NET formation through the NF‐κB signalling pathway. Conclusions Melatonin decreases neutrophil recruitment by suppressing NET formation, exerting a protective effect in periodontitis.
{"title":"Melatonin Alleviates Periodontitis by Suppressing Neutrophil Extracellular Traps–Dependent Neutrophil Recruitment","authors":"Xiao Wu, Jiawei Lu, Zehui Xiong, Jie Huang, Jinyi Zhang, Lijun Luo","doi":"10.1111/jcpe.70067","DOIUrl":"https://doi.org/10.1111/jcpe.70067","url":null,"abstract":"Aim To investigate the impact of neutrophil extracellular traps (NETs) on periodontitis and the regulatory mechanisms by which melatonin alleviates the disease. Materials and Methods The expression of NET markers in periodontitis tissues was detected using multiple immunohistochemical staining. The effect of NETs on periodontitis was explored through in vivo and in vitro experiments. qPCR and transwell migration assay were used to assess neutrophil activation and recruitment. Flow cytometry, micro‐CT and histological staining were employed to evaluate neutrophil recruitment in gingiva and periodontitis progression in a ligature‐induced periodontitis (LIP) mouse model. Melatonin was then administered in vivo and in vitro to evaluate its effects on NET formation, neutrophil activation, neutrophil recruitment and periodontitis progression. Finally, Western blotting and qPCR were employed to elucidate the mechanisms underlying melatonin‐mediated regulation of NET formation. Results NETs were evident in gingival tissues from patients with periodontitis. After inhibiting NET formation, the expression levels of inflammatory cytokines (Il‐1β, Il‐6, Tnf‐α), neutrophil chemokines (Ccl2, Ccl4, Cxcl1) and neutrophil recruitment were found to decrease. Furthermore, melatonin treatment reduced NET formation, decreased neutrophil activation and recruitment and alleviated bone resorption in LIP mice. Mechanistically, melatonin suppresses NET formation through the NF‐κB signalling pathway. Conclusions Melatonin decreases neutrophil recruitment by suppressing NET formation, exerting a protective effect in periodontitis.","PeriodicalId":15380,"journal":{"name":"Journal of Clinical Periodontology","volume":"167 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：