The role of NF-kappaB in the inflammatory processes related to dental caries, pulpitis, apical periodontitis, and periodontitis-a narrative review.

Tooth-related inflammatory disorders, including caries, pulpitis, apical periodontitis (AP), and periodontitis (PD), are primarily caused by resident oral microorganisms. Although these dental inflammatory conditions are typically not life-threatening, neglecting them can result in significant complications and greatly reduce an individual's quality of life. Nuclear factor κB (NF-κB), a family formed by various combinations of Rel proteins, is extensively involved in inflammatory diseases and even cancer. This study reviews recent data on NF-κB signaling and its role in dental pulp stem cells (DPSCs), dental pulp fibroblasts (DPFs), odontoblasts, human periodontal ligament cells (hPDLCs), and various experimental animal models. The findings indicate that NF-κB signaling is abnormally activated in caries, pulpitis, AP, and PD, leading to changes in related cellular differentiation. Under specific conditions, NF-κB signaling occasionally interacts with other signaling pathways, affecting inflammation, bone metabolism, and tissue regeneration processes. In summary, data collected over recent years confirm the central role of NF-κB in dental inflammatory diseases, potentially providing new insights for drug development targeting NF-κB signaling pathways in the treatment of these conditions. Keywords: NF-κB, dental caries, pulpitis, apical periodontitis, periodontitis.

The relationship between severity of periapical periodontitis and next-generation systemic inflammatory biomarkers in children with early childhood caries.

INTRODUCTION: Early childhood caries (ECC) is closely associated with poor oral hygiene and cariogenic diet. Untreated ECC results in recurrent odontogenic infections and local and systemic consequences. In this study, our goal is to assess the relationship between the intensity of odontogenic infection-associated periapical periodontitis and new generation of systemic inflammatory markers (SII, NLR, PLR) in ECC-affected children. MATERIAL AND METHOD: 95 healthy patients in early childhood and demonstrating periapical periodontitis who underwent dental treatment under general anesthesia (GA) in the last two years were included in the present study. Their periapical statuses were dichotomized as mild and severe. Periapical Index (PAI) scores of 2 and 3 were regarded as "mild" whereas 4 and 5 as "severe". Of the complete blood test (CBC) parameters, systemic inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), neutrophilic granulocyte (NEUT), lymphocyte (LYMPH) and platelet (PLT) were recorded. The relationship between the degree of periapical pathology and the evaluated markers was assessed using Receiver Operating Characteristic (ROC) analysis. RESULTS: Results of the present study revealed that mean NLR, SII and NEUT index scores of the patients having severe periapical periodontitis were statistically higher than those of the ones with mild pathology (p < 0.05). A positive, statistically significant interrelationship was found between the number of teeth demonstrating a PAI score of severe periapical periodontitis with the signs of exacerbation (PAI 5) and NLR and SII values (p < 0.05). Area under the ROC curve (AUC) values for NLR and SII were determined as 66.8% and 66.6% respectively, indicating that classification performance was sufficient and statistically significant (p < 0.05). CONCLUSION: Postponing the management of odontogenic infections will induce some complications such as, infective endocarditis and cause the systemic inflammatory process to continue by aggravating the systemic effects of local lesions. Thus, underlying mechanism should be eliminated and oral hygiene should be maintained, also novel biomarkers may be recommended to be used for the decision-making process for the teeth with persistent periapical lesions unresponsive to treatment.

[Introduction and interpretation of The European Society of Endodontology S3-level clinical practice guideline for treatment of pulpal and apical disease].

The European Society of Endodontology published the S3-level clinical practice guideline for the treatment of pulpal and apical disease in October 2023, which provides best current therapeutic strategies supported by scientific evidences. The guideline was divided into four parts: the diagnosis and treatment of pulpitis, diagnosis and nonsurgical treatment of apical periodontitis, surgical treatment of apical periodontitis, and regenerative treatment. This article aims to introduce and interpret the guideline, and to better manage patients with pulpitis and apical periodontitis for preserving teeth over a patient's lifetime in China.

Systemic Factors Affecting Prognosis and Outcome of Endodontic Therapy.

The successful outcome of endodontic treatment is dependent on the immune response and the reparative potential of the individual. Alteration in the host immune response is a common characteristic shared by both apical periodontitis and systemic diseases. Although infection-induced periapical lesions occur in a localized environment, numerous epidemiologic studies in the last few decades have investigated the potential association between endodontic disease pathogenesis and systemic diseases. The goal of this review is to identify common systematic factors and discuss the effect they may or may not have on the prognosis and outcome of endodontic therapy.

α-IRAK-4 Suppresses the Activation of RANK/RANKL Pathway on Macrophages Exposed to Endodontic Microorganisms.

Periapical lesions are common pathologies affecting the alveolar bone, often initiated by intraradicular lesions resulting from microbial exposure to dental pulp. These microorganisms trigger inflammatory and immune responses. When endodontic treatment fails to eliminate the infection, periapical lesions persist, leading to bone loss. The RANK/RANKL/OPG pathway plays a crucial role in both the formation and the destruction of the bone. In this study, the objective was to inhibit the RANK/RANKL pathway in vitro within exposed Thp-1 macrophages to endodontic microorganisms, specifically Enterococcus faecalis, which was isolated from root canals of 20 patients with endodontic secondary/persistent infection, symptomatic and asymptomatic, and utilizing an α-IRAK-4 inhibitor, we introduced endodontic microorganisms and/or lipoteichoic acid from Streptococcus spp. to cellular cultures in a culture plate, containing thp-1 cells and/or PBMC from patients with apical periodontitis. Subsequently, we assessed the percentages of RANK+, RANKL+, and OPG+ cells through flow cytometry and measured the levels of several inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) in the cellular culture supernatant through a CBA kit and performed analysis by flow cytometry. A significant difference was observed in the percentages of RANK+RANKL+, OPG+ RANKL+ cells in thp-1 cells and PBMCs from patients with apical periodontitis. The findings revealed significant differences in the percentages of the evaluated cells, highlighting the novel role of the IRAK-4 inhibitor in addressing this oral pathology, apical periodontitis, where bone destruction is observed.

Brain Abscess in the Contralateral Frontal Lobe Associated with Frontal Sinusitis that Spread from Odontogenic Maxillary Sinusitis.

We encountered a case involving a brain abscess in the right frontal lobe of a 12-year-old girl who was diagnosed with a chief complaint of headache and nausea. Left maxillary sinusitis, a dental infection related to dental caries and apical periodontitis, was observed in the left maxillary first molar in addition to left frontal sinusitis also being present. In addition to administering antibacterial agents, extraction of the left maxillary first molar and drainage of the paranasal sinuses and brain abscess were performed. Follow-up over the course of 1 year and 5 months indicated that the patient had progressed without any sequelae; therefore, the prognosis was good. In this case, although bone destruction was observed in the posterior wall of the frontal sinus, which could be a route for bacteria to enter the skull, we considered the possibility of direct invasion from the same site to be low because the brain abscess occurred on the opposite side. We believe that a route for hematogenous invasion from apical periodontitis, in addition to sinusitis, is also possible. Regardless of the route, the outset was an infection in the dental field; therefore, this case reaffirmed the importance of dental cavity treatment in childhood.

Assessment of Treatment Quality Risk Factors Influencing the Radiographic Detection of Apical Periodontitis in Root-Filled Teeth: A Retrospective CBCT Analysis.

OBJECTIVE: This study aimed to assess the treatment quality factors associated with the risk of radiographic detection of apical periodontitis (AP) in root-filled teeth (RFT) on CBCT images. METHODS: Two hundred eighty-five CBCT scans of patients (range 18-60, mean 35.1) years old were selected from a pool of CBCT scans which were taken from 2016-2022. Gender and age were recorded. The presence/absence of AP, unfilled canal, perforation, zipping and ledge and homogenous/nonhomogeneous root canal filling (RCF), adequate/inadequate coronal restoration and under/over filled RCF and those within 0-2 mm from the radiographic apex were recorded for RFTs. Kappa was used to assess intra-consensus reliability. Chi-square and Binary logistic regression were used to assess and predict risk factors related to the detection of AP. A significant difference was set at p<0.05. RESULTS: AP was present in 81.5% of RFTs. No significant difference was present in the AP prevalence in RFT between males and females, maxilla and mandible, right and left sides, RFT with adequate and inadequate coronal restoration and RFT with/without zipping and ledge and between RFT with overfilled and those with RCF end within 0-2 mm from the radiographic apex (p>0.05), respectively. Significantly higher AP prevalence was present in RFT with unfilled canal, perforations, non-homogenous and underfilled RCF (p<0.05), respectively. The odds of AP detection were 2.02, 5.5, 2 and 1.98 times higher in RFT with unfilled canal, perforations, non-homogenous and underfilled RCF, respectively. Intra-consensus reliability was (0.98, 0.95, 0.85, 0.81, 0.88, 0.85 and 0.92) for AP, unfilled canal, perforation, zipping and ledge, homogeneity of RCF, coronal restoration and length of RCF, respectively. CONCLUSION: The vast majority of teeth with previous root fillings presented with AP. AP detection risk was significantly higher in root-filled teeth with perforation, non-homogeneous, and underfilled root canal filling. Other factors do not influence the radiographic detection of AP in CBCT images. (EEJ-2024-02-042).

Negotiating and Treating Lateral Canals: Report of 7 Cases.

This is a series of 7 cases in which the operator penetrated lateral canals with instruments. Two teeth presented with irreversible pulpitis, 4 with necrotic pulps, and 1 with previous treatment. Except for the teeth with pulpitis, all the others were associated with apical periodontitis. The main root canal was always relatively straight, with the lateral canals at the middle third of the root. Suggestive images of lateral canal presence were seen on periapical radiographs in five cases. The clinician introduced intentionally small hand instruments in the lateral canal in 5 cases, while the penetration was fortuitous in the others. The lateral canals were obturated in all cases. Follow-up examination was possible in five cases, all of them showed evidence of successful clinical and radiographic outcomes. Introducing files into lateral canals may permit some preparation and penetration of irrigant solution, favoring disinfection and, consequently, enhancing the treatment outcome. (EEJ-2023-05-063).

Human Umbilical Cord Mesenchymal Stem Cells-Derived Extracellular Vesicles for Rat Jawbone Regeneration in Periapical Periodontitis.

Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) have great potential for bone remodeling and anti-inflammatory therapy. For the repair and reconstruction of inflammatory jawbone defects caused by periapical periodontitis, bone meal filling after debridement is commonly used in the clinic. However, this treatment has disadvantages such as large individual differences and the need for surgical operation. Therefore, it is of great significance to search for other bioactive substances that can promote jawbone regeneration in periapical periodontitis. Herein, it is found that CT results showed that local injection of human umbilical cord mesenchymal stem cells-derived extracellular vesicles (HUC-MSCs-EVs) and bone meal filling into the alveolar bone defect area could promote bone tissue regeneration using a rat model of a jawbone defect in periapical periodontitis. Histologically, the new periodontal tissue in the bone defect area was thicker, and the number of blood vessels was higher by local injection of HUC-MSCs-EVs, and fewer inflammatory cells and osteoclasts were formed compared to bone meal filling. In vitro, HUC-MSCs-EVs can be internalized by rat bone marrow mesenchymal stem cells (BMSCs), enhancing the ability for proliferation and migration of BMSCs. Additionally, 20 µg/mL HUC-MSCs-EVs can facilitate the expression of osteogenic genes and proteins including runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin (OPN). In summary, in vivo and in vitro experiments showed that HUC-MSCs-EVs can promote bone regeneration in periapical periodontitis, and the effect of tissue regeneration is better than that of traditional bone meal treatment. Therefore, local injection of HUC-MSCs-EVs may be an effective method to promote jawbone regeneration in periapical periodontitis.

Apical periodontitis in osteoporotic postmenopausal women: Systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to analyze the scientific evidence about the association between osteoporosis in postmenopausal women and the prevalence of apical periodontitis, assessed radiographically. MATERIAL AND METHODS: PRISMA Guidelines have been followed. The research question was: In adult women, does the presence or absence of osteoporosis affect the prevalence of AP, radiographically diagnosed? A systematic search was performed in PubMed/MEDLINE, Web of Science, Scopus and EMBASE. The meta-analyses were calculated with the Open Meta Analyst software. Risk of bias was assessed using the Newcastle Ottawa Scale. The certainty of evidence was assessed by GRADE. RESULTS: Four studies were selected. Meta-analysis showed an overall OR = 2.2 (95% CI = 0.94 - 4.97; p = 0.07), indicating that osteoporotic women had approximately twice the probability of having periapical lesions, compared to control women, although the difference was only marginally significant. The overall risk of bias of the included studies was moderate, and the certainty of evidence was low. CONCLUSIONS: Apical periodontitis, assessed as periapical lesion, is more frequently diagnosed in osteoporotic women, who are twice as likely to have periapical radiolucent lesions.

Postoperative pain in oncological patients subjected to nonsurgical root canal treatment: a prospective case-control study.

OBJECTIVES: The purpose of this prospective study was to evaluate the incidence and intensity of postoperative pain in oncological patients with infected teeth subjected to nonsurgical root canal treatment or retreatment. METHODS: Teeth with apical periodontitis from healthy control patients and oncological patients (n = 70 per group) were root canal treated/retreated and evaluated for the development of postoperative pain. Patients from the two groups were matched for tooth type, gender, clinical manifestation of apical periodontitis, and intervention type. A visual analogue scale (VSA) was used to evaluate the incidence of postoperative pain at 24 h, 72 h, 7d, and 15d after chemomechanical procedures. Data were statistically analyzed for the incidence and intensity of postoperative pain in the two groups. RESULTS: Preoperative pain occurred in 10% of the individuals and in all these cases pain showed a reduction in intensity or was absent after endodontic intervention at 24-h evaluation. The overall incidence of postoperative pain at 24 h was 14% in oncology patients and 30% in controls (p = 0.03). At 72 h, the respective corresponding figures were 4% and 8.5% (p > 0.05). At 7 and 15 days, all patients were asymptomatic, irrespective of the group. CONCLUSIONS: No significant differences in postoperative pain were found between control and oncological patients. The low incidence of postoperative pain observed in both groups supports the routine use of nonsurgical root canal treatment/retreatment as valid options in oncological patients. CLINICAL RELEVANCE: Oncological patients had no increased risk of postoperative pain in comparison with control patients.

Evidence of an effect of statins on lesions originating from dental infection. A retrospective clinical investigation.

BACKGROUND: Apical periodontitis (AP) is an inflammatory dental disease caused by bacterial infections of the endodontic system. The correlation between AP and cardiovascular diseases. (CVD) has been consistently investigated. Statins are a class of drugs that are used to treat hypercholesterolemia and prevent atherosclerotic vascular diseases. They have other beneficial pleiotropic effects such as anti-inflammatory, antithrombotic, and antioxidant activities. The aim of this study was to evaluate the oral health status and prevalence of AP in patients treated with statins (Group S) in comparison with untreated patients (Group C) to understand whether the anti-inflammatory action of these drugs can influence the prevalence of AP. METHODS: The records of seventy-nine patients (43 men and 36 women, mean age 68 ± 11 years, 1716 teeth) treated with statins and referred to the University clinic for dental evaluation were reviewed. Seventy patients free from systemic diseases and without therapy (39 men and 31 women, mean age 62 ± 9 years, 1720 teeth) constituted the control group. All subjects underwent complete oral, dental, and radiographic examinations to determine the presence and severity of AP. Periapical index (PAI) and decayed, missed, and filled teeth (DMFT) scores were obtained. RESULTS: AP was significantly less common in Group S (22,8%) than in Group C (50%) (P < 0.05). Furthermore, the mean value of the qualitative rank of the severity of AP (PAI score) was higher in Group C than in Group S (P ≤ 0.05). CONCLUSIONS: Our results suggest that statins can attenuate the prevalence of AP, which is associated to CVD.

The effect of intracanal cryotherapy with and without foraminal enlargement on pain prevention after endodontic treatment: a randomized clinical trial.

This randomized clinical trial aims to evaluate cryotherapy as a therapeutic option for pain prevention after endodontic treatment with and without foraminal enlargement, in patients with asymptomatic apical periodontitis.120 teeth of patients with preoperative Visual Analogue Scale score indicating zero were treated. Specimens were randomly allocated into 4 groups: Control, Cryotherapy (ICT), Foraminal Enlargement (FE), and Cryotherapy and Foraminal Enlargement (ICT + FE). Working length was determined with an Electronic Apex Locator (EAL). Cryotherapy groups passed through a final irrigation protocol using 20 ml (2.5 â„ƒ) of cold saline solution delivered at working length for 5 min. In FE groups a #40 K-file was used up to the 0.0 mark on the EAL display. Obturation was performed and postoperative pain was checked at 6, 12, 24, 48, and 72 h and 7 days after endodontic treatment.All experimental groups showed an increase in the level of postoperative pain, which started to decrease after 12 h. Foraminal enlargement caused a statistically significant increase in postoperativepain compared to ICT and control groups within the first 6 h (p < 0.05). Cryotherapy did not influence postoperative pain, regardless of whether or not foraminal enlargement was performed.

[Comparison of the effects of using iRoot BP plus and MTA apical barrier surgery in young permanent teeth with chronic apical periodontitis].

PURPOSE: To explore the effect of using iRoot BP plus and MTA apical barrier surgery in young permanent teeth with chronic apical periodontitis. METHODS: A total of 122 patients with chronic periapical periodontitis with open root tips of permanent teeth were randomly divided into experimental group (n=61, 61 teeth) and a control group (n=61, 61 teeth). Patients in the experimental group received iRoot BP plus plus apical barrier surgery, while those in the control group received MTA apical barrier surgery. The old periapical index (O-PAI), apical transmission area, efficacy, treatment times, and inflammatory factor levels of the two groups of patients were compared at 3, 6, 9, and 12 months after surgery. SPSS 19.0 software package was used for statistical analysis. RESULTS: At 12 months after surgery, the O-PAI ratings of the experimental group and the control group were (1.48±0.36) and (1.71±0.42), respectively, and the apical transmission area was (0.51±0.14) and (1.09±0.31). There was a significant difference in the O-PAI ratings and apical transmission area between the two groups(P＜0.05). At 3 months, 6 months, and 12 months after surgery, the O-PAI scores of patients in both groups gradually decreased (P＜0.05). After 12 months of treatment, the success rates of the experimental group and the control group were 98.36% and 88.52%, respectively, with significant difference between the two groups (P＜0.05). The treatment frequency of patients in the experimental group and the control group was (3.64±0.58) times and (4.72±0.61) times, respectively, with a significant difference between the two groups(P＜0.05). After 3 months of treatment, the serum hs-CRP levels in the experimental group and the control group were (6.89±1.13) mg/L and (7.25±1.40) mg/L, respectively, with a significant difference compared to pre-treatment(P＜0.05). After 3 months of treatment, the serum IL-6 levels in the experimental group and the control group were (82.04±19.62) mg/L and (87.52±20.85) mg/L, respectively, with significant differences compared to pre-treatment (P＜0.05). There was no significant difference in serum IL-6 and hs-CRP levels between the two groups before and after treatment(P＞0.05). CONCLUSIONS: iRoot BP plus apical barrier surgery for the treatment of chronic apical periodontitis with open permanent teeth can reduce the O-PAI index, decrease the number of postoperative visits, and have a higher postoperative success rate.

Treatment strategy for patient with non-syndromic tooth agenesis: a case report and literature review.

BACKGROUND: Non-syndromic tooth agenesis (NSTA) is a type of ectodermal dysplasia (ED) in which patients with non-syndromic oligodontia may only affect teeth. No pathological findings were found in other tissues of the ectodermal. Herein, we report a case of a NSTA patient with severe dental anxiety and poor oral health. CASE PRESENTATION: A 5-year-old boy without systemic diseases presented as a patient with oligodontia, extensive caries, and periapical periodontitis. Molecular genetic analysis found a mutation in the Ectodysplasin A (EDA) gene, confirming the diagnosis of NSTA. CONCLUSION: Tooth agenesis (TA) is the most common ectodermal developmental abnormality in humans. Non-syndromic oligodontia patients often seek treatment in the department of stomatology. Because of their complex oral conditions, these patients should be provided with a systematic and personalized treatment plan.

Non-surgical treatment of maxillary lateral incisor double dens invaginatus type â ¢ with apical periodontitis.

Dental invagination is an abnormality of the crown or root development induced during tooth germ development when the enamel-forming apparatus or epithelial root sheath overpopulates and folds into the papilla. In severe cases, the invaginated channels are connected to the pulp and periodontal tissues, often causing endodontic and periapical diseases. The complex anatomical pattern of this disease adds difficulty in its preoperative diagnosis and clinical operation. In this paper, we report a case of non-surgical treatment assisted by cone beam CT and microscopy for maxillary lateral incisor double dens invaginatus type Ⅲ (Ⅲa and Ⅲb) with apical periapical infection. After 1-year follow-up, the affected tooth was asymptomatic and the periapical lesion was significantly reduced.

A 12-month randomized controlled trial to assess the efficacy of revitalization of retreated mature incisors with periapical radiolucency in adolescents.

The use of regenrative endodontics is restoring the health status of the root canals of retreated mature teeth is a novel approach. Therefore, the current trial aimed to compare the effectiveness of regenerative endodontic procedures (REPs) to non-surgical root canal retreatment (NS-RCR) in reducing periapical radiolucency over one year for the retreatment of mature incisors with periapical periodontitis. The secondary purpose was to assess clinical success and regain pulp sensibility. A parallel randomized controlled trial, 66 mature incisors with periapical radiolucencies were randomly divided into two equal groups and retreated with either REPs or NS-RCR. At baseline and after 6 and 12 months, teeth were assessed clinically and radiographically using a periapical index (PAI). The Mann-Whitney test was used to analyze nonparametric PAI scores. The Electric pulp test readings were analyzed using the repeated measure analysis of variance (ANOVA). Over the follow-up intervals, there was no significant intergroup difference in the PAI medians, the majority of the teeth displayed a reduction in periapical radiolucency. At the end of the follow-up period, the clinical successes for the REP and NS-RCR groups were 93.9% and 97%, respectively (p = 0.555). Positive pulp sensibility was recorded in 54.54% of cases in the REPs after 12 months. Both approaches showed a comparable diminishing of periapical radiolucencies and equivalent clinical results. A conventional, non-surgical endodontic retreatment may not always be necessary.

High-performing cross-dataset machine learning reveals robust microbiota alteration in secondary apical periodontitis.

Multiple research groups have consistently underscored the intricate interplay between the microbiome and apical periodontitis. However, the presence of variability in experimental design and quantitative assessment have added a layer of complexity, making it challenging to comprehensively assess the relationship. Through an unbiased methodological refinement analysis, we re-analyzed 4 microbiota studies including 120 apical samples from infected teeth (with/without root canal treatment), healthy teeth, using meta-analysis and machine learning. With high-performing machine-learning models, we discover disease signatures of related species and enriched metabolic pathways, expanded understanding of apical periodontitis with potential therapeutic implications. Our approach employs uniform computational tools across datasets to leverage statistical power and define a reproducible signal potentially linked to the development of secondary apical periodontitis (SAP).

Is SWEEPS better than PUI in reducing intracanal bacteria and inflammation in cases of apical periodontitis?

To evaluate the efficacy of SWEEPS mode of the Er: YAG laser(SL) and passive ultrasonic irrigation(PUI) in the eradication of microorganisms and in the inflammation detection by IL-1ß. Thirty patients with chronic apical periodontitis(AP) were allocated into two groups: Group SL-SWEEPS laser activated irrigation(n = 15) and Group PUI-passive ultrasonic irrigation(n = 15). Bacteriological samples were taken before(S1) and after chemomechanical preparation(S2), and then after final irrigation activation(S3). The levels of total bacteria and Streptococci were measured by means of PCR. Blood samples were collected before and 3rd day after treatment. Enzyme-linked immunosorbent assay was used to measure the levels of IL-1ß. The bacterial reduction showed no differences between groups after chemo-mechanical treatment and after irrigant activation(p = 0.590). Post-treatment IL-1ß levels were lower than pretreatment levels in both groups(p < 0.001). SL or PUI application in addition to chemomechanical preparation has similar effects on total bacterial level and inflammation detected by IL-1ß in patients with AP.

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.