OBJECTIVE: To evaluate the clinical and radiographic efficacy of micro crestal flap-alveolar ridge preservation following extraction of mandibular molars with severe periodontitis compared with natural healing, and to preliminarily propose the surgical indication. METHODS: A retrospective analysis was conducted on clinical data from patients with mandibular molars with severe periodontitis either receiving micro crestal flap-alveolar ridge preservation (MCF-ARP group) or undergoing natural healing in department of periodontology, Peking University School and Hospital of Stomatology from September 2013 to June 2021. Cone-beam computed tomography scannings performed before/immediately after extraction (as baseline) and repeated before implantation (after the extraction socket healing) were used to measure the ridge width, height and volumetric changes of the sockets, and the proportion of guided bone regeneration (GBR) during implant therapy were compared between the two groups. RESULTS: Between baseline and healing, significant differences in changes of MCF-ARP group [(8.34±2.81) mm] and natural healing group [(3.82±3.58) mm] in the distances from mandibular canal to center of the tooth socket were recorded (P < 0.001). The ridge width at 1 mm below the most coronal aspect of the crest increased by (3.50±4.88) mm in the MCF-ARP group but decreased by (0.16±5.70) mm in the natural healing group, respectively (P=0.019). After healing, the MCF-ARP group showed the distances from mandibular canal to center of the tooth socket >8 mm in all the cases, with 97.1% exceeding 10 mm. Natural healing group displayed 23.1% of the cases with center bone height < 8 mm and 61.5% exceeding 10 mm. Volume changes at the buccal and lingual aspect as well as the total socket were significantly greater in the MCF-ARP group compared with natural healing group (P < 0.001).At the time of implantation, GBR was performed in 5 out of 68 subjects (8.3%) in the MCF-ARP group, whereas 8 out of 26 subjects (30.8%) in the natural healing group required GBR, reflecting significant difference (P=0.003). CONCLUSION In the sites of mandibular molars with severe periodontitis, when the distances from mandibular canal to center of the tooth socket was not enough (less than 7 mm), clinicians could consider performing the micro crestal flap-alveolar ridge preservation to achieve augmentation for alveolar ridge and reduce the proportion of guided bone regeneration during implant therapy to reduce the difficulty and risk of injuries during implant therapy.
Humans ; Tooth Extraction ; Retrospective Studies ; Surgical Flaps ; Molar/surgery* ; Mandible/surgery* ; Female ; Periodontitis/surgery* ; Male ; Adult ; Middle Aged ; Cone-Beam Computed Tomography ; Alveolar Ridge Augmentation/methods* ; Alveolar Process/surgery* ; Tooth Socket/diagnostic imaging* ; Dental Implantation, Endosseous/methods*

OBJECTIVE: To evaluate the clinical efficacy of clear aligner therapy in patients with severe periodontitis accompanied by pathological tooth displacement in the anterior region. METHODS: This retrospective study analyzed patients diagnosed with severe periodontitis and pathological displacement in the anterior region, who visited both the Periodontics and Orthodontics Departments at Peking University School and Hospital of Stomatology between 2019 and 2022. A total of 26 eligible cases were included in this study. All the patients underwent regular periodontal maintenance throughout the treatment process, and clear aligners were used for orthodontic treatment. Intraoral scans were analyzed by dedicated software to measure and compare occlusal distribution and proximal contact scores before and after orthodontic treatment. Periodontal clinical indicators were assessed at three key time points: before periodontal treatment (T0), before orthodontic treatment (T1), and after orthodontic treatment (T2). All the cases were treated with clear aligner. RESULTS: A total of 217 pathologically displaced anterior teeth from 26 patients were analyzed. Among these, 105 teeth exhibited periodontal pockets [probing depth (PD) ≥5 mm] before periodontal treatment. After clear aligner therapy, the occlusal score improved significantly from 10.35±8.61 to 23.62±9.73 (P < 0.001), and the proximal contact score increased from 13.62±4.73 to 31.62±10.37 (P < 0.001). The median PD decreased significantly from 3.33 mm [interquartile range (IQR)=0.92] at T0 to 2.50 mm (IQR=0.67, P < 0.001) at T1 and remained stable at 2.50 mm (IQR=0.50) after treatment (T2). A significant reduction in PD was observed between T0 and T2 (P < 0.001), but no significant difference was found between T1 and T2 (P=0.948). CONCLUSION Clear aligner therapy demonstrates favorable clinical efficacy in patients with severe periodontitis and pathological anterior tooth displacement. It effectively improves occlusal distribution and proximal contact while maintaining periodontal health in these patients. However, further large-scale prospective controlled studies are needed to verify its long-term clinical outcomes.
Humans ; Retrospective Studies ; Periodontitis/therapy* ; Female ; Male ; Adult ; Tooth Migration/therapy* ; Tooth Movement Techniques/methods* ; Treatment Outcome ; Middle Aged ; Young Adult ; Orthodontic Appliances, Removable

The prevalence of periodontitis in China is as high as 74.2%, making it the leading cause of tooth loss in adults and severely impacting both oral and overall health. The treatment of periodontitis and periodontal tissue regeneration are global challenges of significant concern. GE Shaohua' s group at School and Hospital of Stomatology, Shandong University has focused on the key scientific issue of "remodeling the periodontal inflammatory microenvironment and optimizing tissue repair and regeneration". They have elucidated the mechanisms underlying the persistence of periodontitis, developed bioactive materials to enhance stem cell regenerative properties, and constructed a series of guided tissue regeneration barrier membranes to promote periodontal tissue repair, leading to the establishment of a comprehensive technology system for the treatment of periodontitis. Specific achievements and progress include: (1) Elucidating the mechanism by which key periodontal pathogens evade antimicrobial autophagy, leading to inflammatory damage; developing intelligent antimicrobial hydrogels and nanosystems, and creating metal-polyphenol network microsphere capsules to reshape the periodontal inflammatory microenvironment; (2) Explaining the mechanisms by which nanomaterial structures and electroactive interfaces regulate stem cell behavior, developing optimized nanostructures and electroactive biomaterials, thereby effectively enhancing the regenerative repair capabilities of stem cells; (3) Creating a series of biphasic heterogeneous barrier membranes, refining guided tissue regeneration and in situ tissue engineering techniques, stimulating the body' s intrinsic repair potential, and synergistically promoting the structural regeneration and functional reconstruction of periodontal tissues. The research outcomes of the group have innovated the fundamental theories of periodontal tissue regeneration, broken through foreign technological barriers and patent blockades, established a cascade repair strategy for periodontal regeneration, and enhanced China' s core competitiveness in the field of periodontal tissue regeneration.
Humans ; Stem Cells/physiology* ; Periodontitis/therapy* ; Guided Tissue Regeneration, Periodontal/methods* ; Regeneration ; Biocompatible Materials ; Tissue Engineering/methods*

Periodontitis has become one of the most widespread chronic inflammatory diseases worldwide, affecting roughly 11% of the adult population. In China, periodontal health is notably poor, with less than 10% of individuals over the age of 35 maintaining periodontal health, while the prevalence of periodontitis in middle-aged and elderly populations reaches as high as 82.6%. From a public health perspective, periodontitis not only seriously compromises oral health but is also closely linked to multiple chronic systemic diseases, including cardiovascular disease, diabetes mellitus, and cognitive impairment. A substantial body of cohort studies and meta-analyses consistently demonstrate that patients with periodontitis are at a significantly increased risk of cardiovascular events. Moreover, periodontitis tends to progress more rapidly in individuals with diabetes, highlighting a bidirectional causal relationship between these two conditions. Our research team has maintained a long-term focus on elucidating the relationship between periodontitis and systemic diseases within Chinese community populations. In this review, we comprehensively summarize epidemiological findings on the associations between periodontitis and cardiovascular disease, metabolic syndrome, and cognitive decline, specifically drawing on data from Chinese cohorts. Complementing these observations, animal experiments provide evidence that experimental periodontitis can induce glucose intolerance and accelerate the development of atherosclerotic lesions. At the mechanistic level, we preliminarily validate that mitochondrial DNA efflux and the hematogenous spread of periodontal pathogens may act as biological conduits bridging local periodontal inflammation with systemic pathologies. We also address current challenges in the field, including difficulties in disentangling causal relationships due to confounding comorbidities like diabetes and cardiovascular diseases, which often coexist and influence each other. To advance understanding, there is an urgent need for well-designed longitudinal and interventional studies employing advanced causal inference methods. Ultimately, this work aims to deepen the current knowledge of periodontitis ' systemic effects and to support the development of evidence-based public health strategies for integrating oral health into chronic disease prevention efforts in China.
Humans ; Periodontitis/complications* ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Metabolic Syndrome/etiology* ; Diabetes Mellitus/epidemiology* ; Risk Factors

Rheumatoid arthritis (RA), an autoimmune disease characterized by chronic inflammation of synovial tissue, is divided into two subtypes-anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. While the pathogenic mechanisms of ACPA-positive RA are well-understood, the etiology of ACPA-negative RA remains largely unknown. The association between RA and periodontitis (PD) has been observed since the early 1900s, with the two diseases sharing common genetic and environmental risk factors that lead to the progressive destruction of bone and connective tissue. However, the associations between PD and the two subtypes of RA differ. This comprehensive review aims to provide an updated understanding of the epidemiological association between RA and PD, explore potential pathogenic mechanisms linking the two diseases, and highlight the key distinctions between the subtypes of RA and their respective associations with PD. We also discuss the possibility of early intervention or the treatment of the two diseases. Ultimately, this review aims to provide valuable insights for future research in this field.
Humans ; Arthritis, Rheumatoid/complications* ; Periodontitis/complications* ; Anti-Citrullinated Protein Antibodies/immunology* ; Risk Factors

Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Regenerating periodontal bone defect surrounding periodontal tissue is crucial for orthodontic or dental implant treatment. The declined osteogenic ability of periodontal ligament stem cells (PDLSCs) induced by inflammation stimulus contributes to reduced capacity to regenerate periodontal bone, which brings about a huge challenge for treating periodontitis. Here, inspired by the adhesive property of mussels, we have created adhesive and mineralized hydrogel microspheres loaded with traditional compound cordycepin (MMS-CY). MMS-CY could adhere to the surface of alveolar bone, then promote the migration capacity of PDLSCs and thus recruit them to inflammatory periodontal tissues. Furthermore, MMS-CY rescued the impaired osteogenesis and ligament-forming capacity of PDLSCs, which were suppressed by the inflammation stimulus. Moreover, MMS-CY also displayed the excellent inhibitory effect on the osteoclastic activity. Mechanistically, MMS-CY inhibited the premature senescence induced by the inflammation stimulus through the nuclear factor erythroid 2-related factor (NRF2) pathway and reducing the DNA injury. Utilizing in vivo rat periodontitis model, MMS-CY was demonstrated to enhance the periodontal bone regeneration by improving osteogenesis and inhibiting the osteoclastic activity. Altogether, our study indicated that the multi-pronged approach is promising to promote the periodontal bone regeneration in periodontitis condition by reducing the inflammation-induced stem cell senescence and maintaining bone homeostasis.
Animals ; Bone Regeneration/drug effects* ; Rats ; Periodontal Ligament/cytology* ; Microspheres ; NF-E2-Related Factor 2 ; Hydrogels ; Periodontitis/therapy* ; Osteogenesis/drug effects* ; Disease Models, Animal ; Stem Cells ; Male ; Rats, Sprague-Dawley ; Humans

The increasing aging population and aging-associated diseases have become a global issue for decades. People over 65 show an increased prevalence and greater severity of periodontitis, which poses threats to overall health. Studies have demonstrated a significant association between aging and the dysfunction of neutrophils, critical cells in the early stages of periodontitis, and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion. Neutrophils differentiate and mature in the bone marrow before entering the circulation; during an infection, they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens. Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues. The impacts of aging on neutrophils' chemotaxis, anti-microbial function, cell activation, and lifespan result in impaired neutrophil functions and excessive neutrophil activation, which could influence periodontitis course. We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses. We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging. This review could help us better understand the pathogenesis of periodontitis, which could offer novel therapeutic targets for periodontitis.
Humans ; Neutrophils/immunology* ; Periodontitis/immunology* ; Aging/physiology*