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Background: Periodontitis and atherosclerosis are both chronic inflammatory diseases with a high prevalence. Increasing evidence supports the independent association between severe periodontitis and atherosclerotic cardiovascular disease, in which oral microorganisms may play an important role. We aimed to evaluate the characteristic changes of salivary microbiome and metabolome in patients with carotid atherosclerosis (CAS) and periodontitis., Methods and Results: The subjects were obtained from a cross-sectional study that included 1933 participants aged 40 years or older from rural northeast China. The study enrolled 48 subjects with CAS and 48 controls without CAS matched by sex, age, body mass index, and prevalence of hypertension, diabetes, and dyslipidemia. We performed full-length 16S rDNA gene sequencing and untargeted metabolomics of saliva samples from 96 subjects. We found that CAS was closely associated with an increased abundance of Streptococcus , Lactobacillus , and Cutibacterium . Furthermore, patients with CAS had higher prevalence of severe periodontitis than the control group. Notably, periodontal pathogens such as Tannerella and Anaeroglobus were not only associated with periodontitis but also enriched in patients with CAS, whereas periodontal health-associated Neisseria was more abundant in those without CAS. We also identified 2 lipid metabolism pathways, including glycerophospholipid and sphingolipid metabolism, as associated with CAS. The levels of trimethylamine N -oxide and inflammatory mediator leukotriene D4 were significantly higher in patients with CAS, whereas the levels of carnosine were significantly lower, than those in controls. Additionally, serum levels of inflammatory marker high-sensitivity C-reactive protein were significantly increased in CAS and positively correlated with the abundance of Anaeroglobus and leukotriene D4 in saliva., Conclusions: Our study suggests that characteristic changes in salivary microbiota and metabolites are closely related to CAS, and periodontitis and associated microorganisms may be involved in the initiation and progression of CAS.

Objectives: This systematic review was aimed to evaluate the effect of non-surgical periodontal therapy (NSPT) on hemoglobin A1c (HbA1c) in periodontitis patients without diabetes mellitus (DM)., Data/sources: The present systematic review and meta-analysis were performed through searching the following electronic databases: EMBASE, MEDLINE, Web of Science, Cochrane Library and Open GREY. Interventional studies of periodontitis patients without DM were investigated. HbA1c changes in these patients before and after NSPT were analyzed. Subgroup analysis and sensitivity analysis were employed to identify sources of heterogeneity., Study Selection: Three reviewers independently selected the eligible studies by screening the titles and abstract. Then, a full-text analysis was performed. The reasons for excluding studies were recorded. Any disagreements were settled by discussion with a fourth reviewer. All the four reviewers extracted and crosschecked the data, and disagreements were resolved by discussion. There are 21 case-series studies (self-controlled studies) and 1 non-randomized interventional studies (NRIs) were included., Results: For periodontitis patients without DM, a total of 469 individuals from 22 studies were enrolled. The pooled analysis demonstrated that it was significantly changed in HbA1c levels at 3-month follow-up (0.16 with 95 % CI 0.04, 0.27; P = 0.008), and 6-month follow-up (0.17 % with 95 % CI 0.08, 0.27; P < 0.001) compared with baseline. Smoking, gender, experience of periodontal therapy and HbA1c value at baseline could be the sources of heterogeneity., Conclusions: NSPT is potentially beneficial for the management of HbA1c in periodontitis patients with high risks of DM. However, high-quality randomized controlled trials are still necessary to confirm these conclusions., Clinical Significance: The systemic review evaluated the effect of NSPT on HbA1c in periodontitis patients without DM. The analysis may be beneficial to the management and control of the high risks of DM in periodontitis patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Prevention of atherosclerotic cardiovascular disease (ASCVD) is important in individuals with metabolic syndrome components (MetS), and periodontitis may play an important role in this process. This study aims to evaluate the association between periodontitis and ASCVD in participants with the components of MetS, including obesity, dysglycemia, hypertension, and dyslipidemia., Materials and Methods: This study conducted followed the MOOSE reporting guidelines and the PRISMA 2020 guidelines. EMBASE, MEDLINE, Web of Science, Cochrane Library, PubMed and OpenGrey were searched for observational studies about the linkage of periodontitis to ASCVD in people with MetS components up to April 9, 2023. Cohort, case-control and cross-sectional studies were included after study selection. Quality evaluation was carried out using the original and modified Newcastle-Ottawa Scale as appropriate. Random-effects model was employed for meta-analysis., Results: Nineteen studies were finally included in the quality analysis, and all of them were assessed as moderate to high quality. Meta-analyses among fifteen studies revealed that the participants with periodontitis were more likely to develop ASCVD in those who have dysglycemia (RR = 1.25, 95% CI = 1.13-1.37; p < 0.05), obesity (RR = 1.13, 95% CI = 1.02-1.24; p < 0.05), dyslipidemia (RR = 1.36, 95% CI = 1.13-1.65; p < 0.05), or hypertension (1.20, 95% CI = 1.05-1.36; p < 0.05)., Conclusions: Periodontitis promotes the development of ASCVD in participants with one MetS component (obesity, dysglycemia, hypertension or dyslipidemia)., Clinical Relevance: In people with MetS components, periodontitis may contribute to the ASCVD incidence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The gingiva is a key oral barrier that protects oral tissues from various stimuli. A loss of gingival tissue homeostasis causes periodontitis, one of the most prevalent inflammatory diseases in humans. The human gingiva exists as a complex cell network comprising specialized structures. To understand the tissue-specific pathophysiology of the gingiva, we applied a recently developed spatial enhanced resolution omics-sequencing (Stereo-seq) technique to obtain a spatial transcriptome (ST) atlas of the gingiva in healthy individuals and periodontitis patients. By utilizing Stereo-seq, we identified the major cell types present in the gingiva, which included epithelial cells, fibroblasts, endothelial cells, and immune cells, as well as subgroups of epithelial cells and immune cells. We further observed that inflammation-related signalling pathways, such as the JAK-STAT and NF-κB signalling pathways, were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy individuals. Additionally, we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed gingiva. In conclusion, our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells., (© 2023. Science China Press.)

Periodontitis is an irreversible inflammatory response that occurs in periodontal tissues. Given the size and diversity of natural flora in the oral mucosa, host immunity must strike a balance between pathogen identification and a complicated system of tolerance. The innate immune system, which includes innate lymphoid cells (ILCs), certainly plays a crucial role in regulating this homeostasis because pathogens are quickly recognized and responded to. ILCs are a recently discovered category of tissue-resident lymphocytes that lack adaptive antigen receptors. ILCs are found in both lymphoid and non-lymphoid organs and are particularly prevalent at mucosal barrier surfaces, where they control inflammatory response and homeostasis. Recent studies have shown that ILCs are important players in periodontitis; however, the mechanisms that govern the innate immune response in periodontitis still require further investigation. This review focuses on the intricate crosstalk between ILCs and the microenvironment in periodontal tissue homeostasis, with the purpose of regulating or improving immune responses in periodontitis prevention and therapy., Competing Interests: The authors declare that they have no conflict of interest.

Background: Convincing evidence of the periodontitis as a risk factor for coronary heart disease (CHD) is lacking due to shared risk factors, and no cohort study has investigated the association between CHD and periodontitis in Chinese populations., Methods: This study used a prospective cohort study design. The analysis included 4591 participants aged 40 years and older (3146 men and 1445 women). The association between CHD and periodontitis was estimated using relative risk (RR) calculated using modified Poisson regression. Multiple mediation analysis was used to differentiate the relative effects (RE) from different risk factors on the effect of periodontitis on CHD., Results: In the analysis using the imputed dataset and fully adjusted model, participants with periodontitis at baseline had 37% increased risk of CHD overall compared to those without periodontitis at baseline (RR 1.37; 95% CI 0.96-1.95). Most of the association can be explained by age, sex, history of diabetes, history of hypertension, uric acid and education (RE 0.76; 95% CI 0.41-1.02)., Conclusion: Periodontitis was weakly associated with an increased risk of CHD among the middled-aged and elderly in China. Further studies are required to identify more mediators and elucidate the mechanisms of how periodontitis increases the risk of CHD., (© 2021. The Author(s).)

Mesenchymal stem cell-based therapy is a reliable treatment for periodontal tissue regeneration, while ideal regeneration rate is still a facing problem. In previous study, we found SFRP2 a promising gene in modulating mesenchymal stem cells potential. We further investigated its role on periodontal tissue regeneration. We created periodontitis model in miniature pigs and locally injected with stem cells from apical papilla (SCAP). The periodontitis models were classed into three groups, SFRP2-SCAP group (injected with SCAP overexpressing with SFRP2), SCAP group (injected with SCAP transduced with vector backbone) and saline group (vehicle group injected with saline). Clinical assignment, CT scanning, histopathological assessment and quantitative analysis were applied to evaluate the regeneration effect. Twelve weeks after the injection, we found healthier gingival status in SFRP2-SCAP group than the other two groups. Clinical assignment results showed values of probing depth, gingival recession and attachment loss were improved in SFRP2-SCAP group than that of SCAP group and saline group. The volume of newborn bone was also enhanced in SFRP2-SCAP group than SCAP group and saline group. The difference of clinical assignments and newborn bone between each group was significant relevant. HE staining demonstrated increased tissue regeneration in SFRP2-SCAP group than SCAP group and saline group. Our findings revealed that SFRP2 could enhance SCAP-mediated periodontal tissue regeneration and provide a potential target for improving the regeneration of periodontal tissue., (© 2019 John Wiley & Sons Ltd.)

Objective: The oral microbiota plays a key part in the initial colonization by pathogens and the chronic inflammatory reaction of the host. We measured variations in the salivary microbiota and evaluated their potential associations with periodontitis and chronic obstructive pulmonary disease (COPD). Methods: We investigated the salivary microbiota of patients with COPD and periodontitis ( n = 21) compared with that in patients with periodontitis alone ( n = 36) and with healthy controls (HCs; n = 14), using pyrosequencing of polymerase chain reaction-amplified 16s rRNA genes. Results: Bacterial richness and diversity were significantly higher in patients suffering from COPD, and the bacterial family Lachnospiraceae was observed frequently only among patients with COPD and periodontitis. Veillonella, Rothia, Actinomyces , and Fusobacterium were the core bacterial genera that showed significant differences among patients with coincident COPD and periodontitis, patients with periodontitis alone, and HCs ( p < 0.05). Veillonella, Rothia , and Actinomyces were observed much more frequently in patients with COPD and periodontitis, compared with that in HCs. All tested populations were divided into subgroups based on sex, smoking, or periodontitis index. In the subgroup with a bleeding index >2, Rothia was significantly different in periodontitis with and without COPD groups compared with HCs. In the subgroup with a plaque index >2.5, Rothia and Veillonella showed significant differences in periodontitis with and without COPD groups compared with HCs. Conclusion: Variations in salivary microbiota may be associated with COPD and periodontitis., (Copyright © 2020 Lin, Li, Wang, Cheng, Zhang, Han, Song, Wang and Wang.)

The purpose of this study was to investigate the effects of vitamin D in rat models of chronic obstructive pulmonary disease (COPD) and periodontitis. Animals with both periodontitis and COPD, or with periodontitis only, were established. Once the animal model was established, experimental groups received intraperitoneal injections of 25-hydroxyvitamin D3 (25-OHD3) for 8 weeks, while control groups received refined peanut oil. After sacrifice, inflammatory status was examined in terms of the serum levels of receptor activator of the nuclear factor κB ligand (RANKL), tumor necrosis factor alpha (TNF-α) and interleukins (IL-1 and IL-10), as well as alveolar bone loss, forced expiratory volume (0.20) (FEV 0.20), and the ratio of FEV0.2 to forced vital capacity. The results showed that 25-OHD3 treatment significantly alleviated inflammation by decreasing the serum levels of RANKL, TNF-α and IL-1 and increasing that of IL-10, while reducing alveolar bone loss and slightly improving lung function. These findings suggest that vitamin D supplementation could be a new clinical approach for the treatment of COPD and periodontitis.

Background: Discovering suitable seeding cells and simple application technique will be beneficial for MSC-mediated treatment of periodontitis. Stem cells from apical papilla (SCAPs) might be the candidate seeding cell for the periodontal tissues regeneration based on their origin and characters. In this research, we investigated the effect of SCAPs on periodontal tissue regeneration in swine by local injection., Methods: We established experimental periodontitis model in miniature pigs and then treated them with SCAPs by local injection. Clinical assessments, computed tomography (CT) scanning, histologic examination, and quantitative measurements were used to evaluate the effect of periodontal tissues regeneration., Results: At 12 weeks after injection, clinical assessments showed that probing depth, gingival recession, and attachment loss values were 5.44±0.77 mm versus 7.33±1.0 mm (p<0.01), 2.33±0.33 mm versus 2.11±0.69 mm (p>0.05), and 7.78±0.84 mm versus 9.44±1.07 mm (p<0.01) in SCAPs group and 0.9% NaCl group, respectively. CT scan results showed a significant increase of 12.86 mm 3 alveolar bone regeneration in SCAPs group compared with 0.9% NaCl group. In addition, histopathology results demonstrated remarkable regeneration in SCAPs group, whereas regeneration of periodontal tissue was hardly found in 0.9% NaCl group., Conclusion: Local injection of SCAPs could effectively restore tissue defects brought about by periodontitis in the swine model. Thus, SCAPs, as an easily accessible dental-deriving stem cell, may serve as an alternative application for periodontitis treatment.

Background: Periodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model., Methods: In the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3 mm in depth. hDPSCs were obtained for bone regeneration using cell injection or cell sheet transplantation. After 12 weeks, clinical, radiological, and histological assessments of regenerated periodontal tissues were performed to compare periodontal regeneration treated with xenogeneic cell injection and cell sheet implantation., Results: Our study showed that translating hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC injection significantly improved periodontal tissue healing clinically in comparison with the control group. The volume of regenerative bone in the hDPSC sheet group (52.7 ± 4.1 mm(3)) was significantly larger than in the hDPSC injection group (32.4 ± 5.1 mm(3)) (P < 0.05). The percentage of bone in the periodontium in the hDPSC injection group was 12.8 ± 4.4 %, while it was 17.4 ± 5.3 % in the hDPSC sheet group (P < 0.05)., Conclusion: Both hDPSC injection and cell sheet transplantation significantly regenerated periodontal bone in swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC injection.

Background: Regeneration of lost periodontium in periodontitis is a challenge in that alveolar bone, cementum, and periodontal ligament need to be restored to their original architecture. Stem cells from exfoliated deciduous teeth (SHEDs) appear to be an attractive candidate for periodontium tissue regeneration. Previously, the authors successfully regenerated periodontal defects using autologous and allogeneic periodontal ligament stem cells (PDLSCs). The purpose of the present study is to investigate the ability of allogeneic SHEDs to regenerate lost periodontium in a swine periodontitis model., Methods: Animal models of periodontitis were established in miniature pigs, and allogeneic stem cells were isolated from miniature pig deciduous teeth (SPDs). The animal models were treated with SPDs plus hydroxyapatite/tricalcium phosphate (HA/TCP). Allogeneic PDLSCs plus HA/TCP or HA/TCP alone were set as positive control or control, respectively. Clinical assessments, computed tomography (CT) scanning, and histologic examination were used to evaluate the outcome of tissue regeneration., Results: Clinical indices including probing depth, gingival recession, and attachment loss showed significant restoration in the SPD and PDLSC treatment groups, compared to the HA/TCP group 12 weeks post-transplantation. Meanwhile, CT scans showed that 75% of the samples had successful hard-tissue regeneration in both PDLSC and SPD groups, compared to the HA/TCP group, where the success rate was only 25%. In addition, histologic examination demonstrated that SPD and PDLSC treatment brought about remarkable regeneration of periodontal tissues, whereas periodontal regeneration was rare in the HA/TCP group., Conclusions: Allogeneic SPDs can effectively repair hard and soft tissue loss brought about by periodontitis in a swine model. Allogeneic SHEDs, which are easily accessible, may be applied to treat periodontitis in clinics in the future.

Periodontitis is one of the most widespread infectious diseases in humans. It is the main cause of tooth loss and associated with a number of systemic diseases. Until now, there is no appropriate method for functional periodontal tissue regeneration. Here, we establish a novel approach of using allogeneic periodontal ligament stem cells (PDLSCs) sheet to curing periodontitis in a miniature pig periodontitis model. Significant periodontal tissue regeneration was achieved in both the autologous and the allogeneic PDLSCs transplantation group at 12 weeks post-PDLSCs transplantation. Based on clinical assessments, computed tomography (CT) scanning, and histological examination, there was no marked difference between the autologous and allogeneic PDLSCs transplantation groups. In addition, lack of immunological rejections in the animals that received the allogeneic PDLSCs transplantation was observed. Interestingly, we found that human PDLSCs fail to express human leukocyte antigen (HLA)-II DR and costimulatory molecules. PDLSCs were not able to elicit T-cell proliferation and inhibit T-cell proliferation when stimulated with mismatched major histocompatibility complex molecules. Furthermore, we found that prostaglandin E2 (PGE2) plays a crucial role in PDLSCs-mediated immunomodulation and periodontal tissue regeneration in vitro and in vivo. Our study demonstrated that PDLSCs possess low immunogenicity and marked immunosuppression via PGE2-induced T-cell anergy. We developed a standard technological procedure of using allogeneic PDLSCs to cure periodontitis in swine.

Periodontitis is a periodontal tissue infectious disease and the most common cause for tooth loss in adults. It has been linked to many systemic disorders, such as coronary artery disease, stroke, and diabetes. At present, there is no ideal therapeutic approach to cure periodontitis and achieve optimal periodontal tissue regeneration. In this study, we explored the potential of using autologous periodontal ligament stem cells (PDLSCs) to treat periodontal defects in a porcine model of periodontitis. The periodontal lesion was generated in the first molars area of miniature pigs by the surgical removal of bone and subsequent silk ligament suture around the cervical portion of the tooth. Autologous PDLSCs were obtained from extracted teeth of the miniature pigs and then expanded ex vivo to enrich PDLSC numbers. When transplanted into the surgically created periodontal defect areas, PDLSCs were capable of regenerating periodontal tissues, leading to a favorable treatment for periodontitis. This study demonstrates the feasibility of using stem cell-mediated tissue engineering to treat periodontal diseases.

Background: A high detection rate of diabetes among dental visitors has been reported recently. This systematic review aimed to evaluate the association between periodontitis and glycated hemoglobin (HbA1c) levels among non-diabetic individuals. Methods: The EMBASE, MEDLINE, Web of Science, Cochrane Library, PubMed, and Open GREY databases were searched, and observational studies published until 1st June 2023 were identified. A methodological quality assessment was conducted based on the original and modified versions of the Newcastle–Ottawa scale. Cohort, case–control, and cross-sectional studies that performed clinical periodontal examinations and measured HbA1c levels in non-diabetic adults were included. A meta-analysis was conducted to estimate the weighted mean difference (WMD) between individuals with and without periodontitis. Results: In total, 29 case–control and 5 cross-sectional studies were selected from 2583 potentially eligible articles. Among them, sixteen case–control and three cross-sectional studies with moderate to high quality were selected for the meta-analyses. The HbA1c levels in periodontitis patients were significantly higher than those in individuals with healthy periodontal conditions (WMD = 0.16; p < 0.001) among the non-diabetic populations. Conclusions: This study reveals a significant association between periodontitis and HbA1c levels in non-diabetic populations. Thus, HbA1c screening may be recommended to detect potential hyperglycemia in non-diabetic periodontitis patients. [ABSTRACT FROM AUTHOR]

Stem cell-mediated tissue regeneration is a promising strategy for repairing tissue defects and functional reconstruction in periodontitis, a common disease that leads to the loss of alveolar bone and teeth. However, stem cell apoptosis, widely observed during tissue regeneration, impairs its efficiency. Therefore, the regulation of stem cell apoptosis is critical for improving regeneration efficiency. The LIM homeobox 8 gene LHX8, belongs to the LIM homeobox family, which was involved in tooth morphogenesis. Here, we found that LHX8 was significantly expressed in dental pulp. LHX8 knockdown significantly increased dental pulp mesenchymal stem cells (DPSCs) apoptosis, as confirmed by RT-PCR, western blotting, flow cytometry, and transmission electron microscopy. Additionally, LHX8 overexpression inhibited apoptosis and enhanced the osteo/odontogenic differentiation potential of hDPSCs in vitro. Furthermore, LHX8 -overexpression could enhance the periodontal tissue regeneration efficiency of hDPSCs in mice with periodontitis. In conclusion, the present study indicates that LHX8 inhibits stem cell apoptosis and promotes functional tissue formation in stem cell-based tissue regeneration engineering, suggesting a new therapeutic target to increase the efficacy of periodontal tissue regeneration. • LHX8 was significantly expressed in dental pulp. • LHX8 regulate mesenchymal stem cells apoptosis. • LHX8 overexpression promoted the formation of tissue regeneration function of hDPSCs. • LHX8 suppressed the expression of BAD and BAK. [ABSTRACT FROM AUTHOR]

Background: The relationship between chronic periodontitis and pulpal/cemental changes is seldom reported. This study aimed to report on the microstructural changes of cementum and histopathological features of the dental pulp in teeth with severe chronic periodontitis.Methods: Eighty molar teeth with severe chronic periodontitis and 50 extracted third molars (as normal controls) were collected. The microstructure of cementum was evaluated by scanning electron microscopy, and the pulp was stained with hematoxylin and eosin. Interleukin (IL)-17 and IL-1β levels were examined by immunohistochemistry/western blotting. Reactive oxygen species (ROS) and superoxide dismutase 1 (SOD 1) levels were also checked. Caspase 3 expression and terminal-deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used as apoptotic indices, and LC3B and P62 were detected to demonstrate the level of autophagy.Results: The surface of cementum showed irregularities; the dental pulp was inflamed and under oxidative stress. IL-17 and IL-1β levels were increased in the pulp of teeth with periodontitis. ROS and apoptosis levels were higher than in normal dental pulp, while SOD 1 level was reduced. Intriguingly, autophagy markers LC3B and P62 were upregulated in the pulp obtained from teeth with periodontitis.Conclusions: Severe chronic periodontitis influenced the microstructure of both cementum and dental pulp. The dental pulp collected from teeth with periodontitis was inflamed, under oxidative stress, and presented increased levels of apoptosis and autophagy relative to normal dental pulp. [ABSTRACT FROM AUTHOR]

Periodontal ligament stem cells (PDLSCs) have provided novel cell sources for tooth and periodontal tissue regeneration. Allogeneic PDLSCs can reconstruct periodontal ligament tissue that has been damaged by periodontal diseases and regulate T-cell immunity. However, the effect of PDLSCs on B cells remains unknown. Here, we treated periodontitis in a miniature pig model using allogeneic PDLSCs and showed a reduction in humoral immunity in the animals. When cocultured with normal B cells, human PDLSCs (hPDLSCs) had similar effects as bone marrow mesenchymal stem cells in suppressing B cell proliferation, differentiation, and migration, while intriguingly, hPDLSCs increased B cell viability by secreting interleukin-6. Mechanistically, hPDLSCs suppressed B cell activation through cell-to-cell contact mostly mediated by programmed cell death protein 1 and programmed cell death 1 ligand 1. Our data revealed a previously unrecognized function of PDLSCs in regulating humoral immune responses, which may represent a novel therapeutic strategy for immune-related disorders. S TEM C ells 2013;31:1371-1382 [ABSTRACT FROM AUTHOR]

Aim The purpose of this study was to investigate the immunomodulatory properties of periodontal ligament stem cells derived from inflamed periodontal ligament tissues. Material and Methods Periodontal ligament stem cells were identified and isolated from healthy or inflamed periodontal ligament tissues. Peripheral blood mononuclear cells were cocultured with inflamed or healthy periodontal ligament stem cells, and T-lymphocyte proliferation was determined by incubation with carboxyfluorescein succinimidyl ester. T-helper cells (Th1/Th2, Th17) and regulatory T cells were analysed by flow cytometry. Cytokine profiles in supernatants were tested with a cytometric bead array. Results Compared to healthy cells, inflamed periodontal ligament stem cells showed significantly diminished inhibition of T-cell proliferation. In cocultures, stimulated peripheral blood mononuclear cells showed significantly less induction of CD4+ CD25+ FOXP3+ regulatory T cells and IL-10 secretion in the presence of inflamed compared with healthy periodontal ligament stem cells. Furthermore, suppression of Th17 differentiation and IL-17 production by inflamed periodontal ligament stem cells was significantly lesser than by healthy cells. Conclusion This study demonstrated that inflamed periodontal ligament stem cells had markedly dysfunctional immunomodulatory properties; this may contribute to an imbalanced immune response, acceleration of osteoclastogenesis and inflammatory alveolar bone loss in periodontitis. [ABSTRACT FROM AUTHOR]