OBJECTIVES: This study aims to explore the therapeutic targets of curcumin in periodontitis through network pharmacology and molecular docking technology. METHODS: Targets of curcumin and periodontitis were predicted by different databases, and the protein-protein interaction (PPI) network constructed by String revealed the interaction between curcumin and periodontitis. The key target genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was performed to analyze the binding potential of curcumin to periodontitis. RESULTS: A total of 672 periodontitis-related disease targets and 107 curcumin-acting targets were obtained from the databases, and 20 key targets were screened. The GO and KEGG analyses of the 20 targets showed that curcumin might play a therapeutic role through the hypoxia-inducible factor (HIF)-1 and parathyroid hormone (PTH) signaling pathways. Molecular docking analysis showed that curcumin had good binding potential with multiple targets. CONCLUSIONS The potential key targets and molecular mechanisms of curcumin in treating periodontitis provide a theoretical basis for new drug development and clinical applications.
Humans ; Network Pharmacology ; Curcumin/therapeutic use* ; Molecular Docking Simulation ; Periodontitis/drug therapy* ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b⁺ macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b⁺ macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b⁺ macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b⁺ macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b⁺ macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the "core" and mouse neutrophil membrane as the "shell" was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b⁺ macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b⁺ macrophages, and suggests a CD301b⁺ macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.
Animals ; Mice ; Bone Regeneration ; Cytokines/metabolism* ; Interleukin-4/therapeutic use* ; Macrophages/physiology* ; Mammals ; Osteogenesis ; Periodontitis/drug therapy*

Conventional periodontal regenerative surgery has limited effect on tooth with severe periodontitis-related alveolar bone defects. This article reported a case of regenerative treatment in severe distal-bone defect of mandibular first molar. The treatment involved applying 3D printing, advanced/injectable platelet-rich fibrin, and guided tissue-regeneration technology. After the operation, the periodontal clinical index significantly improved and the alveolar bone was well reconstructed.
Humans ; Platelet-Rich Fibrin ; Follow-Up Studies ; Digital Technology ; Furcation Defects/drug therapy* ; Periodontitis ; Guided Tissue Regeneration, Periodontal

Once pulp necrosis or apical periodontitis occurs on immature teeth, the weak root and open root apex are challenging to clinicians. Berberine (BBR) is a potential medicine for bone disorders, therefore, we proposed to apply BBR in root canals to enhance root repair in immature teeth. An in vivo model of immature teeth with apical periodontitis was established in rats, and root canals were filled with BBR, calcium hydroxide or sterilized saline for 3 weeks. The shape of the roots was analyzed by micro-computed tomography and histological staining. In vitro, BBR was introduced into stem cells from apical papilla (SCAPs). Osteogenic differentiation of stem cells from apical papilla was investigated by alkaline phosphatase activity, mineralization ability, and gene expression of osteogenic makers. The signaling pathway, which regulated the osteogenesis of SCAPs was evaluated by quantitative real time PCR, Western blot analysis, and immunofluorescence. In rats treated with BBR, more tissue was formed, with longer roots, thicker root walls, and smaller apex diameters. In addition, we found that BBR promoted SCAPs osteogenesis in a time-dependent and concentration-dependent manner. BBR induced the expression of β-catenin and enhanced β-catenin entering into the nucleus, to up-regulate more runt-related nuclear factor 2 downstream. BBR enhanced root repair in immature teeth with apical periodontitis by activating the canonical Wnt/β-catenin pathway in SCAPs.
Animals ; Berberine ; pharmacology ; Cell Differentiation ; drug effects ; Dental Papilla ; Male ; Osteogenesis ; drug effects ; Periapical Periodontitis ; therapy ; Rats ; Stem Cells ; cytology ; drug effects ; metabolism ; Wnt Signaling Pathway ; drug effects ; Wnt3A Protein ; genetics ; metabolism ; X-Ray Microtomography

Efforts to control inflammation and achieve better tissue repair in the treatment of periodontitis have been ongoing for years. Human β-defensin 3, a broad-spectrum antimicrobial peptide has been proven to have a variety of biological functions in periodontitis; however, relatively few reports have addressed the effects of human periodontal ligament cells (hPDLCs) on osteogenic differentiation. In this study, we evaluated the osteogenic effects of hPDLCs with an adenoviral vector encoding human β-defensin 3 in an inflammatory microenvironment. Then human β-defensin 3 gene-modified rat periodontal ligament cells were transplanted into rats with experimental periodontitis to observe their effects on periodontal bone repair. We found that the human β-defensin 3 gene-modified hPDLCs presented with high levels of osteogenesis-related gene expression and calcium deposition. Furthermore, the p38 MAPK pathway was activated in this process. In vivo, human β-defensin 3 gene-transfected rat PDLCs promoted bone repair in SD rats with periodontitis, and the p38 mitogen-activated protein kinase (MAPK) pathway might also have been involved. These findings demonstrate that human β-defensin 3 accelerates osteogenesis and that human β-defensin 3 gene modification may offer a potential approach to promote bone repair in patients with periodontitis.
Animals ; Anti-Infective Agents ; metabolism ; pharmacology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Humans ; Osteogenesis ; drug effects ; Periodontal Ligament ; drug effects ; metabolism ; Periodontitis ; drug therapy ; Rats ; Rats, Sprague-Dawley ; beta-Defensins ; metabolism ; pharmacology

OBJECTIVE: To evaluate the clinical efficacy of clarithromycin (CLM) in the adjuvant treatment of chronic periodontitis systematically, obtain reasonable conclusions through evidence-based medicine, and provide guidance for clinical rational drug use. METHODS: Literature about CLM in the adjuvant treatment of chronic periodontitis was searched in CNKI, VIP, Wanfang, Chinese Biomedical Literature Database, PubMed, ScienceDirect, and Embase databases from inception to February 2019 using a computer. Meta-analysis was performed on the homogeneous study using RevMan 5.3 software after two independent reviewers screened the literature, evaluated the quality of the study, extracted the data, and evaluated the risk of bias in the included studies. RESULTS: Six randomized controlled trials were included in 316 subjects. The meta-analysis showed that compared with the scaling and root planning (SRP) group, the probing depth (PD) was reduced in patients with CLM and SRP [MD=-1.00, 95%CI (-1.55, -0.45), P=0.000 04]. Clinical attachment loss was obtained [MD=-0.03, 95%CI (0.43, 0.65), P<0.000 01], and the difference between the groups was statistically significant. The modified sulcus bleeding index (mSBI) was reduced [MD=-0.01, 95%CI (-0.14, 0.19), P=0.66]. No significant difference was observed between the groups, but the decrease in mSBI was more significant in CLM combined with SRP group. CONCLUSIONS CLM combined with subgingival SRP can achieve remarkable results in treating chronic periodontitist.
Anti-Bacterial Agents ; therapeutic use ; Chronic Periodontitis ; drug therapy ; Clarithromycin ; Dental Scaling ; Humans ; Periodontal Index ; Root Planing ; Treatment Outcome

Periodontitis patients are at risk of alveolar bone loss during orthodontic treatment. The aim of this study was to investigate whether intermittent parathyroid hormone (1-34) treatment (iPTH) could reduce alveolar bone loss during orthodontic tooth movement (OTM) in individuals with periodontitis and the underlying mechanism. A rat model of OTM in the context of periodontitis was established and alveolar bone loss was observed. The control, iPTH and iPTH + stattic groups received injections of vehicle, PTH and vehicle, or PTH and the signal transducer and activator of transcription 3 (STAT3) inhibitor stattic, respectively. iPTH prevented alveolar bone loss by enhancing osteogenesis and suppressing bone resorption in the alveolar bone during OTM in rats with periodontitis. This effect of iPTH was along with STAT3 activation and reduced by a local injection of stattic. iPTH promoted osteoblastic differentiation and might further regulate the Wnt/β-catenin pathway in a STAT3-dependent manner. The findings of this study suggest that iPTH might reduce alveolar bone loss during OTM in rats with periodontitis through STAT3/β-catenin crosstalk.
Animals ; Homeostasis ; Humans ; Osteogenesis ; Parathyroid Hormone ; Periodontitis/drug therapy* ; Rats ; STAT3 Transcription Factor/metabolism* ; Tooth Movement Techniques ; beta Catenin

Periodontitis is an inflammatory autoimmune disease. Treatment should alleviate inflammation, regulate the immune reaction and promote periodontal tissue regeneration. Icariin is the main active ingredient of Epimedii Folium, and it is a promising compound for the enhancement of mesenchymal stem cell function, promotion of bone formation, inhibition of bone resorption, alleviation of inflammation and regulation of immunity. The study investigated the effect of icariin on periodontal tissue regeneration in a minipig model of periodontitis. The minipig model of periodontitis was established. Icariin was injected locally. The periodontal clinical assessment index, a computed tomography (CT) scan, histopathology and enzyme-linked immune sorbent assay (ELISA) were used to evaluate the effects of icariin. Quantitative analysis results 12 weeks post-injection demonstrated that probing depth, gingival recession, attachment loss and alveolar bone regeneration values were (3.72 ± 1.18) mm vs. (6.56 ± 1.47) mm, (1.67 ± 0.59) mm vs. (2.38 ± 0.61) mm, (5.56 ± 1.29) mm vs. (8.61 ± 1.72) mm, and (25.65 ± 5.13) mm vs. (9.48 ± 1.78) mm in the icariin group and 0.9% NaCl group, respectively. The clinical assessment, CT scan, and histopathology results demonstrated significant enhancement of periodontal tissue regeneration in the icariin group compared to the 0.9% NaCl group. The ELISA results suggested that the concentration of interleukin-1 beta (IL-1β) in the icariin group was downregulated compared to the 0.9% NaCl group, which indicates that local injection of icariin relieved local inflammation in a minipig model of periodontitis. Local injection of icariin promoted periodontal tissue regeneration and exerted anti-inflammatory and immunomodulatory function. These results support the application of icariin for the clinical treatment of periodontitis.
Animals ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flavonoids ; administration & dosage ; pharmacology ; Gingival Crevicular Fluid ; chemistry ; Inflammation ; drug therapy ; Periodontitis ; diagnostic imaging ; drug therapy ; Swine ; Swine, Miniature ; Tomography, X-Ray Computed

This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the alpha1-adrenergic receptor (alpha1-AR) and beta2-adrenergic receptor (beta2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of alpha1-AR and beta2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1beta, IL-6 and IL-8 were detected after pretreatment with the alpha1/beta2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, alpha1-AR and beta2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of alpha1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of alpha1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1beta, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an alpha1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.
Adrenergic alpha-1 Receptor Antagonists/*therapeutic use ; Animals ; Cells, Cultured ; Cytokines/immunology ; Fibroblasts/immunology/pathology ; Humans ; Lipopolysaccharides/administration & dosage/immunology ; Male ; Periodontal Ligament/cytology/immunology/pathology ; Periodontitis/*drug therapy/*etiology/immunology/pathology ; Phentolamine/*therapeutic use ; Rats ; Rats, Wistar ; Receptors, Adrenergic, alpha-1/analysis/*immunology ; Signal Transduction/drug effects ; *Stress, Physiological/drug effects ; Tyrosine 3-Monooxygenase/analysis/immunology

This study was designed to assess the effectiveness of a modified silk ligature twisted with wire for inducing advanced periodontitis. Periodontitis was induced in five premolars and one molar of 20 healthy dogs over a 60-day period. The dogs were divided into four groups according to the ligature-inducing materials used: soft moistened food only, wire ligature (WL), silk ligature (SL) and twisted ligature with silk and wire (SWL). Periodontal indices were recorded, and dental radiographs were taken before and after 60 days of ligation. The ligatures were checked daily and the day the ligature fell out was noted. The period during which the ligatures were maintained was significantly shorter for the SL group compared to the SWL group (p < 0.05). Results of the clinical examination showed that almost all periodontal status parameters including the plaque index, gingival index, clinical attachment level, and bleeding on probing were significantly exacerbated in the SWL group compared to the other groups (p < 0.05). Radiographic evaluation demonstrated that alveolar bone levels were significantly lower in the SWL group than the other groups on day 60 (p < 0.05). These results suggested that experimental periodontitis induced by SWL could be an effective method for investigating periodontitis in canine models.
Alveolar Bone Loss/veterinary ; Analgesics, Opioid/therapeutic use ; Animals ; Dog Diseases/*pathology ; Dogs ; Ligation/instrumentation/methods/*veterinary ; Materials Testing/veterinary ; Pain/drug therapy/veterinary ; Periodontitis/pathology/*veterinary ; Tramadol/therapeutic use