Periapical Bone Research Articles

Clinical management of mandibular permanent premolars with periapical lesion and bilateral supernumerary teeth: A 7-years follow-up case report

Objectifs: This 7-years follow-up case report describes two diversified strategies for the management of bilateral mandibular permanent premolars associated with periapical lesion and unerupted supernumerary teeth. Case Report: A non-syndromic 9 years-old Asian female patient presented pain and swelling of the 35 in anatomical contiguity with an immature and unerupted supernumerary tooth. Clinical examination revealed an intraoral vestibular sinus tract related to the necrotic 35. Periapical radiography and CBCT showed that the 35 had an immature apex associated with a periapical lesion, and a supernumerary tooth in a lingual direction. Endodontic treatment of the 35 was performed by creating an apical plug with ProRoot MTA, while the supernumerary tooth was monitored radiographically with no intervention. Four years later, the 45 developed the same clinical condition of the left arch. Radiographic examination revealed a periapical lesion with massive periapical bone resorption, and a supernumerary tooth in normal alignment. The second premolar was herein extracted to allow for eruption of the supernumerary tooth. Outcomes: 3-years follow-up revealed continued root maturation and its spontaneous eruption in the dental arch. Proper healing of both mandibular lesions was monitored after 10 months, 3-years and 7-years revealing no recurrence on both sides.

CD34 and Ki-67 Immunoexpression in Periapical Granulomas: Implications for Angiogenesis and Cellular Proliferation.

The main mechanism of the formation of granulation tissue is the progression of an infection from the tooth to the periapical bone. At this level, the immune system tries to localize and annihilate the microorganism's injury. Ki-67 is a protein directly associated with the cell proliferation rate, while CD34 is a biomarker involved in angiogenesis, and studies suggest that they both have a positive correlation with the intensity of the local inflammatory infiltrate. This study will determine the immunoexpression of CD34 and Ki-67 in periapical granulomas and assess their impact on the growth and development of this tissue, as well as consider their roles in the proliferative process and aggressiveness of evolution. In the present study, 35 periapical granulomas obtained after a tooth extraction were included. The specimens were analyzed via histopathology and immunohistochemistry. A positive reaction for the Ki-67 antibody was observed in 32 (86.5%) of the 35 periapical granuloma cases included in our study. We identified the overexpression of Ki-67 and CD34 and further calculated the Ki-67 index to evaluate and correlate the proliferation potential and angiogenesis with regard to the presence of an inflammatory infiltrate. These findings suggest that the persistence of an inflammatory environment directly influences Ki-67 and CD34 expression, sustaining the proliferative capacity of cells and abnormal angiogenesis. This study is the first to evaluate the presence of the CD34+ and Ki-67+ proliferating vessels in periapical granulomas.

Retratamento endodôntico de dente portador de lesão periapical extensa com presença de núcleo metálico

This study aims to present a clinical case of retreatment of a tooth with an extensive periapical lesion with the presence of a metal core. A 59-year-old patient was referred for dental treatment due to the need for retreatment of tooth 22. During clinical examination, the presence of a fistula was observed and the patient reported pain on vertical and horizontal percussion, absence of a periodontal pocket, and radiographic examination showed extensive periapical bone radiolucency, presence of filling material, as well as a fused metal core. After removal of the metal core with the aid of ultrasound, retreatment was performed with rotary instrumentation (Prodesign Logic RT). Sodium hypochlorite at 2.5% was used as the irrigating solution. The root canal system was obturated using the single cone technique associated with BIO-C Sealer cement. It is concluded that endodontic retreatment after removal of a fused metal core can be performed in a single session and determine the success of endodontic therapy.

Automating Dental Condition Detection on Panoramic Radiographs: Challenges, Pitfalls, and Opportunities.

Background/Objectives: The integration of AI into dentistry holds promise for improving diagnostic workflows, particularly in the detection of dental pathologies and pre-radiotherapy screening for head and neck cancer patients. This study aimed to develop and validate an AI model for detecting various dental conditions, with a focus on identifying teeth at risk prior to radiotherapy. Methods: A YOLOv8 model was trained on a dataset of 1628 annotated panoramic radiographs and externally validated on 180 radiographs from multiple centers. The model was designed to detect a variety of dental conditions, including periapical lesions, impacted teeth, root fragments, prosthetic restorations, and orthodontic devices. Results: The model showed strong performance in detecting implants, endodontic treatments, and surgical devices, with precision and recall values exceeding 0.8 for several conditions. However, performance declined during external validation, highlighting the need for improvements in generalizability. Conclusions: YOLOv8 demonstrated robust detection capabilities for several dental conditions, especially in training data. However, further refinement is needed to enhance generalizability in external datasets and improve performance for conditions like periapical lesions and bone loss.

Successful Regenerative Endodontic Therapy of a Dens Evaginatus Mandibular Second Premolar with an Acute Apical Abscess and Extensive Periapical Bone Loss: A Case Report.

Regenerative endodontics is a rapidly growing field within dentistry that aims to replace damaged tooth structures and cells of the pulp-dentin complex. This case report presents the successful management of an immature permanent second mandibular premolar with an acute apical abscess and extensive apical bone loss caused by a dens evaginatus. This tooth was unexpectedly treated with long-term calcium hydroxide (Ca(OH)2) that was replenished several times over 6 months. During the treatment process, this tooth became reinflamed developing a chronic apical abscess after resolution of the initial acute apical abscess, which resulted in the replacement and prolonged use of Ca(OH)2. The final regenerative procedures were completed using a bioceramic fast set putty placed directly over the blood clot and an occlusal composite restoration. At the 6-month follow-up, the patient was asymptomatic with a fully healed radiographic lesion, new periodontal ligament, and the apex closed with thickening of the mesial and distal aspects of the root. At the 15-month follow-up, the patient remained asymptomatic with continued evidence of radiographic development of the apical aspect of this tooth, displaying root end closure and thickening. This is a unique case report of the management of a complex infection process in an immature tooth with regenerative techniques with repeated and long-term use of Ca(OH)2. This novel report provides dental practitioners with a new potential protocol for the management of these immature cases with advanced periapical infections that require extensive disinfection to have successful outcomes.

The influence of systemic factors on the prognosis of apical periodontitis

Apical periodontitis (AP) is an inflammatory disease that occurs in the periapical tissue. The treatments of AP mainly include root canal therapy and endodontic surgery which promote the repair of periapical bone tissue by infections clearing and controlling inside or outside the root canal. The evaluation on efficacies of root canal therapy and endodontic surgery is mainly based on clinical and periapical imaging examinations, and the prognosis relates to multiple factors. The systemic factors of patients can directly or indirectly affect the healing of apical periodontitis. The present review summarizes the influence factors, including age, smoking habits, systemic diseases and systemic medication on the prognosis of apical periodontitis treatment, in order to increase the attention of clinicians.

TRATAMENTO ENDODÔNTICO DO PRIMEIRO PRÉ-MOLAR SUPERIOR COM EXTRAVASAMENTO DE CIMENTO OBTURADOR – RELATO DE CASO

This study aims to describe a clinical case of endodontic treatment with leakage of filling cement. Patient 30 years old, male, Caucasian, referred to the private office for endodontic treatment of tooth 14. Radiographic examination showed communication with the pulp chamber and absence of periapical bone radiolucency. After anesthesia and coronary opening, the toxic content was neutralized with a K-File 10 manual file and electronic odontometry with apical locator (Root ZX Mini, Morita, Osaka, Japan and root canal preparation with Logic 25.05 (Easy Equipamentos odontológicas- Belo Horizonte – Brazil), foraminal enlargement exceeding 1 millimeter of the real length of the tooth and, with the help of Easy Clean and this time 2% chlorhexidine gel irrigating solution, shaking it 3 cycles of 20 seconds, then 3 cycles with Edta 17 %, completed with saline. Filling the root canal system with a single cone and Bio-C Sealer cement (Angelus –Londrina -Brazil) and restoration with RC Flow Opallis resin. to the apical region.

Diagnostic accuracy of periapical radiography and panoramic radiography in the detection of apical periodontitis: a systematic review and meta-analysis.

Apical periodontitis (AP) is one of the most common pathologies of the oral cavity. An early and accurate diagnosis of AP lesions is crucial for proper management and planning of endodontic treatments. This study investigated the diagnostic accuracy of periapical radiography (PR) and panoramic radiography (PAN) in the detection of clinically/surgically/histopathologically confirmed AP lesions. A systematic literature review was conducted in accordance with the PRISMA guidelines. The search strategy was limited to English language articles via PubMed, Embase and Web of Science databases up to June 30, 2023. Such articles provided diagnostic accuracy values of PR and/or PAN in the detection of AP lesions or alternatively data needed to calculate them. Twelve studies met inclusion criteria and were considered for the analysis. The average value of diagnostic accuracy in assessing AP lesions was 71% for PR and 66% for PAN. According to different accuracy for specific anatomical areas, it is recommended to use PR in the analysis of AP lesions located in the upper arch and lower incisor area, whereas lower premolar and molar areas may be investigated with the same accuracy with PR or PAN. Two-dimensional imaging must be considered the first-level examination for the diagnosis of AP lesions. PR had an overall slightly higher diagnostic accuracy than PAN. Evidence from this review provided a useful tool to support radiologists and dentists in their decision-making when inflammatory periapical bone lesions are suspected to achieve the best clinical outcome for patients, improving the quality of clinical practice.

Lesão endodôntica primária sumulando uma lesão endo-perio

This study aims to present a clinical case of retreatment with the regression of an endodontic lesion, which simulated an endospinal lesion, with monthly changes of calcium hydroxide paste (UltraCal®) and preservation of the lesion repair. A 47-year-old female patient was referred for dental treatment due to the need for retreatment in elements 45 and 46. On clinical examination, the presence of a periodontal pocket fistula of more than 10 millimeters on the mesia and distal surface, respectively, was observed. Cone-beam computed tomography demonstrated the presence of filling material, as well as periapical and lateral bone radiotransparency. The retreatment was performed with rotary instrumentation (Reciproc Blue®), and the preparation of the canal with Reciproc Blue. 2.5% Sodium Hypochlorite was used as an irrigating solution, and the intracanal medication used was calcium hydroxide paste (UltraCal®) and crown sealing was done with glass ionomer cement. After 3 months, a regression of the lesion was observed, at 6 months, treatment success was observed only with endodontic therapy, without the need for periodontal treatment, confirming the diagnosis of primary endodontic lesion with secondary periodontal involvement. It is concluded that endodontic retreatment associated with intracanal medication determined clinical and radiographic success, ruling out the need for periodontal therapy.

Gut microbiota dysbiosis links chronic apical periodontitis to liver fibrosis in nonalcoholic fatty liver disease: Insights from a mouse model.

In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis. Sixteen 7-week-old male apolipoprotein E knockout (apoE-/-) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography-mass spectrometry (LC-MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues. Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group. This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.

Synthetic high-density lipoprotein (sHDL): a bioinspired nanotherapeutics for managing periapical bone inflammation

Apical periodontitis (AP) is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth (i.e., dental pulp tissue), resulting in inflammation and apical bone resorption affecting 50% of the worldwide population, with more than 15 million root canals performed annually in the United States. Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago, such as calcium hydroxide, zinc oxide–eugenol, or even formalin products. Here, we present, for the first time, a nanotherapeutics based on using synthetic high-density lipoprotein (sHDL) as an innovative and safe strategy to manage dental bone inflammation. sHDL application in concentrations ranging from 25 µg to 100 µg/mL decreases nuclear factor Kappa B (NF-κB) activation promoted by an inflammatory stimulus (lipopolysaccharide, LPS). Moreover, sHDL at 500 µg/mL concentration markedly decreases in vitro osteoclastogenesis (P < 0.001), and inhibits IL-1α (P = 0.027), TNF-α (P = 0.004), and IL-6 (P < 0.001) production in an inflammatory state. Notably, sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation, mainly by downregulating at least 3-fold the pro-inflammatory genes, such as Il1b, Il1a, Il6, Ptgs2, and Tnf. In vivo, the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to (1.3 ± 0.05) mm3 and attenuated the inflammatory reaction after treatment to (1 090 ± 184) cells compared to non-treated animals that had (2.9 ± 0.6) mm3 (P = 0.012 3) and (2 443 ± 931) cells (P = 0.004), thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.

Osteoinductive and regenerative potential of premixed calcium-silicate bioceramic sealers on vascular wall mesenchymal stem cells.

The osteogenic potential of new premixed calcium-silicate-containing bioceramic sealers (Ca-Si sealers) was tested with porcine vascular wall-mesenchymal stem cells (pVW-MSCs). Two Ca-Si-containing sealers: Ceraseal (MetaBiomed, Cheong-si, South Korea) and AH Plus Bioceramic (Maruchi, Wonju-si, South Korea), and an epoxy resin sealer (AH Plus; Dentsply, Konstanz, Germany) as a control, were prepared according to the manufacturers' indications. All samples were allowed to set for 100% of their setting time in a sterile humid cabinet at 37°C and 95% relative humidity. pVW-MSC seeding efficiency and osteogenic differentiation were analysed as marker of gene/protein expression for up to 12 days. Mineralization assay and immunofluorescence staining were performed and evaluated over a period of 21 days. Statistical analyses were conducted using one-way analysis of variance (p < .05). Additional samples were prepared and stored under the same conditions and inspected using an environmental scanning electron microscope equipped with an energy dispersive X-ray spectroscopy system. Significantly higher cell seeding efficiency (p < .05) was observed for both Ca-Si sealers from day 8. pVW-MSCs showed a significant shift towards the osteogenic lineage only when seeded in contact with Ca-Si sealers. Gene expression of osteopontin was upregulated significantly. Collagen I and osteocalcin were clearly expressed by cells in contact with Ca-Si sealers. Mineralization granules were observed in Alizarin red assays and confocal laser scanning microscopy analysis of both Ca-Si sealers. No gene expression or granule mineralization were observed on the epoxy resin sealer. Premixed Ca-Si sealers displayed a higher potential for osteogenic activity on pVW-MSCs. Epoxy resin sealer was unable to induce any osteogenic activity. The properties of both Ca-Si sealers suggest their potential as osteoinductive platforms for vascular MSCs in periapical bone.

Mitochondrial biogenesis disorder and oxidative damage promote refractory apical periodontitis in rat and human.

To elucidate whether mitochondrial biogenesis disorder and damage from oxidative stress promote refractory apical periodontitis (RAP) in rat and human. Twenty Enterococcus faecalis-induced RAPs were established in the maxillary first molars of male Wistar rats. Concurrently, 12 periapical lesion specimens from patients presenting with RAP were obtained by apicoectomy. Radiographic examination and histologic analysis were conducted to evaluate periapical bone tissue destruction and morphological changes. The expression of key regulators of mitochondrial biogenesis, PGC-1α and Nrf2, were detected by immunohistochemistry and double immunofluorescence staining, Western blot and real-time PCR were also assayed. Mitochondrial ROS (mtROS) was identified by MitoSOX staining. Mitochondrial function was detected by the quantification of ATP production, mitochondrial DNA (mtDNA) copy number and activities of mitochondrial respiratory chain complexes. Furthermore, mitochondrial oxidative stress was evaluated by the determination of 3-nitrotyrosine (3-NT), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-deoxyguanosine (8-OHdG) expression levels, as well as malondialdehyde (MDA) expression and antioxidant capacity. Student's t-test was performed to determine significance between the groups; p < .05 was considered significant. In the maxilla, significantly more bone resorption, greater number of periapical apoptotic cells and Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were observed in the RAP group compared with the control group (p < .01). PGC-1α and Nrf2 were significantly reduced in rat and human RAP lesions compared to the control group (p < .01) at both the mRNA and protein levels. Double immunofluorescence analysis of PGC-1α or Nrf2 with TOMM20 also indicated that mitochondrial biogenesis was impaired in RAP group (p < .01). Additionally, mitochondrial dysfunction was observed in RAP group, as reflected by increased mtROS, decreased ATP production, reduced mtDNA copy number and complexes of the mitochondrial respiratory chain. Finally, the expression levels of mitochondrial oxidative stress markers, 3-NT, 4-HNE and 8-OHdG, were significantly increased in the RAP group (p < .01). Consistent with this, systemic oxidative damage was also present in the progression of RAP, including increased MDA expression and decreased antioxidant activity (p < .01). Mitochondrial biogenesis disorder and damage from oxidative stress contribute to the development of RAP.

Clinical and Radiographic Evaluation of Mineral Trioxide Aggregate and Human Amniotic Membrane Pulpotomy in Primary Molars: A Randomized Clinical Trial.

To clinically and radiographically compare the outcomes of pulpotomy with mineral trioxide aggregate (MTA) and human amniotic membrane (HAM) in primary molar teeth at 1, 3, 6, and 12 months. The study was a randomized clinical trial with two arms. One arm consisted of participants whose pulpotomy was conducted using MTA, called group I, and the other arm, using HAM, was designated group II. Both MTA and HAM exhibited 100% clinical success. Also, there were no signs of external resorption, periapical bone destruction, or internal resorption in both the MTA and the HAM groups at all four time intervals in this study. However, periodontal ligament widening was seen in 30% of the participants in the MTA group at 1-month and at the 12-month follow-up, whereas in the HAM group, periodontal ligament widening was found to reduce significantly from 22.2% at 1-month to 11.1% at the 12-month follow-up. The HAM exhibited favorable clinical and radiographic outcomes in the present study. Mineral trioxide aggregate is the most preferred choice as a pulpotomy agent for deciduous teeth. However, various drawbacks associated with MTA have been fueling the need for newer, effective agents. HAM is not only easily available, cost-effective, and easy to handle but also favors tissue regeneration. The positive outcome of the present study strongly advocates the use of HAM as an alternative to MTA for pulpotomy in primary teeth. Joseph EJ, Rao A, Mahabala KY, et al. Clinical and Radiographic Evaluation of Mineral Trioxide Aggregate and Human Amniotic Membrane Pulpotomy in Primary Molars: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2024;17(6):641-646.

Incorporation of technology in endodontic treatment of a patient with chronic non-progressive encephalopathy: case report

Objective: This work aims to describe the endodontic treatment performed in a single session in a patient with chronic non-progressive encephalopathy under general anesthesia, using technological devices. Method: A 31-year-old male patient diagnosed with chronic non-progressive encephalopathy, sought dental treatment due to tooth pain. He presented ataxia, atrophy of the upper and lower limbs and involuntary spasms. In the intraoral examination a generalized excessive occlusal wear and temporary restoration on tooth 46 was seen. Periapical radiograph showed increased periodontal space and periapical bone rarefaction. The indication was for endodontic treatment of tooth 46 under general anesthesia. After surgical risk assessment and pre-anesthetic evaluation, endodontic treatment was performed under general anesthesia, using an apical locator, mechanized instrumentation and digital radiography. The tooth restauration was performed in the same clinical moment, without complications. Result: The 8-month follow-up showed absence clinical signs and symptoms and radiographic control without periapical changes. Conclusion: In this case, the incorporation of technology in the endodontic treatment of a patient with chronic non-progressive encephalopathy ensured a safe and effective treatment for the patient and the staff, with case resolution, promotion of oral health and quality of life.

Evaluation of Root Canal Treatment in Chronic Periapical Abscess of Central Incisor

Introduction: trauma to the maxillary anterior teeth is often encountered, especially in teenagers. Severe trauma can result in pulp death and even periapical lesions if left untreated. This case report aims to evaluate periapical lesions in root canal treatment with anterior tooth fractures. Case report: A 21-year-old man came to RSGM UMY with complaints of a broken left front tooth. Teeth have been broken since early high school, around 16 years old. Clinical examination showed tooth 21 an Ellis class II fracture with caries in the fracture area in the mid and distal teeth. Apart from that, there was a vesicular lesion on the mucosa parallel to tooth 21 at 5 mm above the gingival margin, which was painless. Based on radiograph examination, a fracture of 1/3 of the crown is visible, there is a periapical lesion with a lesion size of approximately 5 mm, the lamina dura and periodontal ligament are broken in the apical 1/3. Case management: Root canal treatment was performed on tooth 21 to eliminate or reduce bacteria in the root canal. The sealer for treatment uses eugenol based. Results: The results showed that there was a significant change in the apical lesion at the beginning of the visit until the second control was carried out. Conclusion: Adequate root canal treatment can cure periapical lesions and bone regeneration in cases of chronic periapical abscess

Bone Regeneration on Chronic Apical Abscess After Root Canal Treatment

Chronic Apical Abscess is explained as an inflammatory reaction to pulp infection and necrosis. It is characterized by intermittent discharge of pus through an intraoral sinus tract and usually associated with little or no discomfort. On radiograph examination showed radiolucency as signs of periapical bone destruction. Root canal treatment can elimination bacteria as source of the infection in root canal system. Purpose: these two case report aims to present the management of chronic apical abscess with bone destruction in periapical area. Case report: (1) A 21-years-old female came to complained of a lack of self-confidence due to her upper-front tooth was broken about 8 years ago. Clinical examination showed no discomfort on percussion test, negative on palpation and vitality test. Periapical radiography showed a radiolucent with clear but indistinct boundaries, oval in shape with a diameter of approximately 4 mm. (2) A 20-years-old male complained that his front teeth were broken and discoloured. This complaint had been felt for a long time about 7 years ago. The patient had felt spontaneous pain in the tooth that was hit during the accident for a week. Currently, the tooth is no longer painful. There is no swelling in the gum area where the tooth has changed colour. Radiological examination showed bone damage with a periapical radiolucent appearance with diffuse oval borders with a diameter of 5-6 mm. The diagnosis of these two cases were pulp necrosis with chronic apical abscess. Root canal treatment were performed to elimination bacteria of source infection. First case was restoration using composite resin crown with fiber post intracanal restoration and the second case was restoration using direct restoration. Conclusion: proper root canal treatment resulting bone regeneration and periapical lesions healing in chronic apical abscess cases.

Effects of melatonin against experimentally induced apical periodontitis in rats.

Apical periodontitis is an inflammatory condition resulting from microbial invasion in the root canal system, causing periapical tissue destruction and bone resorption. This study investigated melatonin's effects, known for its antioxidant and anti-inflammatory properties, on experimentally induced apical periodontitis in rats. Three groups of rats were studied: control, apical periodontitis and apical periodontitis with melatonin treatment. Proinflammatory cytokines and enzyme levels in blood serum were measured, and micro-CT analysis assessed bone resorption. Results showed significantly elevated cytokines and enzyme levels in the apical periodontitis group compared to the control. However, in the melatonin-treated group, these levels were significantly reduced (p < 0.01-0.001). Micro-CT analysis indicated decreased periapical resorption cavity volume and surface area with melatonin treatment. This suggests that systemic melatonin administration can mitigate inflammation and reduce bone resorption in experimentally induced apical periodontitis in rats, potentially holding promise for human endodontic disease treatment pending further research.

Influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis in Wistar rats.

The aim of this study was to investigate the influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis (AP) in Wistar rats. Fifty-six rats were submitted to pulp exposure of the lower left first molar for the induction of AP. On the same day, intraperitoneal antibiotic therapy was administered once a day, for 15days, until euthanasia. The groups were formed according to the different treatments (n = 8): C-control; GEN-treated with gentamicin (10mg/Kg); AC-treated with amoxicillin (100mg/Kg); MZ-treated with metronidazole (40mg/Kg); AMP-treated with ampicillin (100mg/Kg); AMC group-treated with amoxicillin + clavulanic acid (100mg/kg); CLI-treated with clindamycin (60mg/kg). After euthanasia, the jaws were collected and processed for (1) histological and histometric analysis using hematoxylin and eosin staining, (2) analysis of collagen fibers using Picrosirius Red staining and (3) bacteriological analysis using Brown-Brenn staining. The data were analyzed statistically (p < 0.05). AP induction was confirmed in all groups. The AMC group had the lower intensity of inflammatory infiltrate (p = 0.028) and less periapical bone resorption compared to control (p = 0.006). Regarding collagen maturation, PSR staining revealed a predominance of mature collagen fibers in all groups. The AC and AMC groups had the lower amount of mature fibers and the highest amount of immature fibers, compared to all other groups (p < 0.001). All groups showed bacterial contamination; however, the AC and AMC groups showed a lower extent of bacterial contamination compared to the control (p < 0.001). It can be concluded that systemic antibiotic therapy influences the development and progression of induced AP.

Metformin switches cell death modes to soothe the apical periodontitis via ZBP1.

Apical periodontitis (AP) is a disease caused by pathogenic microorganisms and featured with the degradation of periapical hard tissue. Our recent research showed the crucial role of Z-DNA binding protein 1 (ZBP1)-mediated necroptosis and apoptosis in the pathogenesis of AP. However, the specific regulatory mechanisms of ZBP1 in AP are not fully elucidated. It was found that metformin has a regulatory role in cell necroptosis and apoptosis. But whether and how metformin regulates necroptosis and apoptosis through the ZBP1 in the context of AP remains unknown. This study provided evidence that lipopolysaccharide (LPS) promotes the synthesis of left-handed Z-nucleic acids (Z-NA), which in turn activates ZBP1. Knockout of Zbp1 by CRISPR/Cas9 technology significantly reduced LPS-induced necroptosis and apoptosis invitro. By using Zbp1-knockout mice, periapical bone destruction was alleviated. Moreover, type I interferon induced the expression of interferon-stimulated genes (ISGs), which serve as a major source of Z-NA. In addition, the RNA-editing enzyme Adenosine Deaminase RNA specific 1 (ADAR1) prevented the accumulation of endogenous Z-NA. Meanwhile, metformin suppressed the ZBP1-mediated necroptosis by inhibiting the expression of ZBP1 and the accumulation of ISGs. Metformin also promoted mitochondrial apoptosis, which is critical for the elimination of intracellular bacterial infection. The enhanced apoptosis further promoted the healing of infected apical bone tissues. In summary, these results demonstrated that the recognition of Z-NA by ZBP1 plays an important role in AP pathogenesis. Metformin suppressed ZBP1-mediated necroptosis and promoted apoptosis, thereby contributing to the soothing of inflammation and bone healing in AP.