Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption.

Introduction: Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to explore whether hypoxic dental pulp stem cells (DPSCs) can promote osteoclastogenesis in orthodontically induced inflammatory root resorption (OIIRR). Methods: Succinate in the supernatant of DPSCs under normal and hypoxic conditions was measured by a succinic acid assay kit. The culture supernatant of hypoxia-treated DPSCs was used as conditioned medium (Hypo-CM). Bone marrow-derived macrophages (BMDMs) from succinate receptor 1 (SUCNR1)-knockout or wild-type mice were cultured with conditioned medium (CM), exogenous succinate or a specific inhibitor of SUCNR1 (4c). Tartrate-resistant acid phosphatase (TRAP) staining, Transwell assays, qPCR, Western blotting, and resorption assays were used to evaluate osteoclastogenesis-related changes. Results: The concentration of succinate reached a maximal concentration at 6 h in the supernatant of hypoxia-treated DPSCs. Hypo-CM-treated macrophages were polarized to M1 proinflammatory macrophages. Hypo-CM treatment significantly increased the formation and differentiation of osteoclasts and increased the expression of osteoclastogenesis-related genes, and this effect was inhibited by the specific succinate inhibitor 4c. Succinate promoted chemotaxis and polarization of M1-type macrophages with increased expression of osteoclast generation-related genes. SUCNR1 knockout decreased macrophage migration, M1 macrophage polarization, differentiation and maturation of osteoclasts, as shown by TRAP and NFATc1 expression and cementum resorption. Conclusions: Hypoxic DPSC-derived succinate may promote osteoclast differentiation and root resorption. The regulation of the succinate-SUCNR1 axis may contribute to the reduction in the OIIRR.

Resorptions and orthodontics / Résorptions et orthodontie

Introduction: It's generally accepted that one of the risks associated with orthodontic treatment is apical root resorption, even though this may occur outside orthodontic treatment. In any case, it causes root shortening. Orthodontists are probably the only dental surgeons who use the inflammatory process as a therapeutic tool. They need to be aware of the risk factors for root inflammation. Along with recurrence, leukemia and periodontal problems, resorption is one of the "inconveniences" of orthodontics, which, if not inevitable, must at least be minimized. Material and Method: At present, the orthodontic literature on root resorption provides some clues as to the factors associated with the onset, severity and management of root resorption, although the complexity of this phenomenon does not allow us to arrive at a clear and unequivocal consensus. For this reason, it is important to identify potential risk factors for resorption, to take them into account before/during and after treatment, and to know what attitude to adopt in the event of resorption appearing, all in order to minimize this phenomenon, as everyone agrees that it can be a source of harm and stress for both patient and practitioner. Conclusion: There are still many grey areas in our understanding of the phenomenon, including how the elements of orthodontic treatment influence orthodontic resorption. Irreversible in nature, resorption can be sufficiently extensive to cast doubt on the benefit of successful orthodontic treatment.

Introduction: Il est généralement admis que l'un des risques associés au traitement orthodontique est la résorption radiculaire apicale même si elle peut se produire en dehors de tout traitement orthodontique. Quoi qu'il en soit, elle provoque le raccourcissement radiculaire. Les orthodontistes sont sans doute les seuls spécialistes de la chirurgie dentaire qui utilisent le processus inflammatoire en tant que moyen thérapeutique. Ils doivent connaître les facteurs de risque de cette inflammation sur la racine. La résorption fait partie, au même titre que la récidive, les leucomes et les problèmes parodontaux, des « inconvénients ¼ de l'orthodontie qui, à défaut d'être inévitables, doivent au moins être minimisés. Matériels et méthode: Actuellement, la littérature orthodontique sur la résorption radiculaire fournit quelques pistes sur les facteurs associés à l'apparition, la gravité et la gestion de la résorption radiculaire, même si la complexité de ce phénomène ne nous permet pas d'en dégager un consensus clair et équivoque. Pour cette raison, il est important d'identifier les facteurs de risque de résorption potentiels pour en tenir compte avant/pendant et après le traitement et connaître l'attitude à adopter en cas d'apparition de résorptions, tout ceci afin de minimiser ce phénomène, car tout le monde s'accorde sur le fait qu'elle peut être source de préjudice et de stress pour le patient et le praticien. Conclusion: De nombreuses zones d'ombres subsistent dans la compréhension du phénomène, notamment sur comment les éléments du traitement orthodontique influencent la résorption orthodontique. De nature irréversible, la résorption peut être suffisamment étendue pour jeter un doute sur le bénéfice apporté au succès du traitement orthodontique.

Full life cycle changes of low impacted mandibular third molar associated cystic lesions and adjacent tooth root resorption: a retrospective study.

OBJECTIVE: Low impacted third molars are usually asymptomatic and are often found by X-ray examination. The removal of asymptomatic low impacted third molars is one of the most controversial clinical issues in oral and maxillofacial surgery. METHODS: In this study, 806 patients with low impacted mandibular third molars (LIMTMs) (full bony impaction) were analyzed to determine the prevalence and risk factors for cystic lesions and adjacent tooth root resorption throughout the patients' entire life cycle. RESULTS: The results showed that the prevalence of adjacent tooth root resorption and cystic lesions was age-related, exhibiting a trend of first increasing and then decreasing; prevalence peaked at the age of 41 to 45 years old, the prevalence rates were 12.50% and 11.11% respectively. And the lowest prevalence rate was 2.86% and 2.44% in ≥ 61 group and 56- to 60-year age group respectively. Age was an independent risk factor for adjacent tooth root resorption of LIMTMs, whereas age and impaction type (especially inverted impaction) were independent risk factors for cystic lesions. CONCLUSIONS: The full life cycle management strategy for LIMTMs may need to be individualized. Surgical removal is recommended for LIMTMs in patients younger than 41 to 45 years, especially for inverted, mesioangular, and horizontally impacted LIMTMs. LIMTMs in patients older than 41 to 45 years may be treated conservatively with regular follow-up, but surgical removal of inverted impacted LIMTMs is still recommended to avoid cyst formation.

Murine IRF8 Mutation Offers New Insight into Osteoclast and Root Resorption.

Interferon regulatory factor 8 (IRF8), a transcription factor expressed in immune cells, functions as a negative regulator of osteoclasts and helps maintain dental and skeletal homeostasis. Previously, we reported that a novel mutation in the IRF8 gene increases susceptibility to multiple idiopathic cervical root resorption (MICRR), a form of tooth root resorption mediated by increased osteoclast activity. The IRF8 G388S variant in the highly conserved C-terminal motif is predicted to alter the protein structure, likely impairing IRF8 function. To investigate the molecular basis of MICRR and IRF8 function in osteoclastogenesis, we generated Irf8 knock-in (KI) mice using CRISPR/Cas9 technique modeling the human IRF8G388S mutation. The heterozygous (Het) and homozygous (Homo) Irf8 KI mice showed no gross morphological defects, and the development of hematopoietic cells was unaffected and similar to wild-type (WT) mice. The Irf8 KI Het and Homo mice showed no difference in macrophage gene signatures important for antimicrobial defenses and inflammatory cytokine production. Consistent with the phenotype observed in MICRR patients, Irf8 KI Het and Homo mice demonstrated significantly increased osteoclast formation and resorption activity in vivo and in vitro when compared to WT mice. The oral ligature-inserted Het and Homo mice displayed significantly increased root resorption and osteoclast-mediated alveolar bone loss compared to WT mice. The increased osteoclastogenesis noted in KI mice is due to the inability of IRF8G388S mutation to inhibit NFATc1-dependent transcriptional activation and downstream osteoclast specific transcripts, as well as its impact on autophagy-related pathways of osteoclast differentiation. This translational study delineates the IRF8 domain important for osteoclast function and provides novel insights into the IRF8 mutation associated with MICRR. IRF8G388S mutation mainly affects osteoclastogenesis while sparing immune cell development and function. These insights extend beyond oral health and significantly advance our understanding of skeletal disorders mediated by increased osteoclast activity and IRF8's role in osteoclastogenesis.

Multiple External Cervical Resorption Lesions in Patient with Graft versus Host Disease Treated with Systemic Bleomycin: A Case Report.

The phenomenon of multiple external cervical root resorption (ECRR) lesions in a single patient is rare but may have a link with the chemotherapeutic agent bleomycin. This case details an adult male with multiple ECRR lesions that developed following chemotherapy. His treatment regimen for Hodgkin's lymphoma included the chemotherapeutic antibiotic bleomycin, which has previously been linked with development of multiple ECRR lesions. The patient developed graft versus host disease following an allogeneic stem cell transplant, which could have a significant role in the development and promotion of the ECRR lesions. In total, 8 teeth developed ECRR, and all the known causative factors were excluded when examined. To our knowledge, this is only the second reported case in the literature to link bleomycin to multiple ECRR lesions. This case report aims to bring the reader's attention to the fact that multiple cervical resorption lesions can develop simultaneously. These lesions can be difficult to diagnose and treat and are often misdiagnosed as caries. Finally, the reader should consider the possible role of bleomycin and graft versus host disease in development of multiple lesions of ECRR.

Histological effects of photobiomodulation on delayed tooth replantation: a systematic review.

This systematic review evaluated preclinical studies to assess whether PBM has a more favorable histological response than other treatments used before delayed replantation of avulsed teeth. This review followed the PRISMA checklist and was registered in PROSPERO. MEDLINE (PubMed), Embase, Scopus and Web of Science were searched from their inception to July 14, 2022. Data were independently extracted by two reviewers. Data were collected about species, number of animals, number and type of teeth, groups evaluated, extra-alveolar time, parameters for PBM and other study groups, presence and characteristics of containment, observation time points, evaluation methods, characteristics evaluated, and significant results. The ARRIVE and SYRCLE tools were used to assess the methodological quality and risk of bias (RoB) of the studies. After screening, six studies were included in the review synthesis. Three of the four studies that evaluated root resorption as an outcome found that PBM decreases its occurrence after delayed tooth replantation. A meta-analysis was not conducted because some data were missing in the included studies. Half of the studies evaluating ankylosis found an increase in its occurrence after PBM. Two studies evaluated inflammatory responses and found a reduction of inflammation after PBM. In general, studies had high methodological heterogeneity, intermediate reporting quality and high RoB. Despite the methodological quality and RoB limitations of the studies, the histological responses after delayed tooth replantation were more favourable in the PBM groups. Preclinical studies supported by guidelines should define laser parameters for future clinical studies.

Attenuation of orthodontically induced inflammatory root resorption by using low-intensity pulsed ultrasound as a therapeutic modality- a systematic review.

Ultrasound is an effective tool for both diagnostic and therapeutic applications. As an imaging tool, ultrasound has mostly been used for real-time noninvasive diagnostic imaging. As ultrasound propagates through a material, a reflected radio-frequency (RF) signal is generated when encountering a mismatch in acoustic impedance. While traditionally recognized for its diagnostic imaging capabilities, the application of ultrasound has broadened to encompass therapeutic interventions, most notably in the form of Low-Intensity Pulsed Ultrasound (LIPUS). Low-Intensity Pulsed Ultrasound (LIPUS) is a form of mechanical energy transmitted transcutaneously by high-frequency acoustic pressure waves. The intensity of LIPUS (30 mW/cm2) is within the range of ultrasound intensities used for diagnostic purposes (1-50 mW/cm2) and is regarded as non-thermal, non-destructive, permeating living tissues and triggering a cascade of biochemical responses at the cellular level. The LIPUS device produces a 200 µs burst of 1.5 MHz acoustic sine waves, that repeats at a modulation frequency of 1 kHz and provides a peak pressure of 30 mW/cm2. Low-intensity pulsed ultrasound (LIPUS) forms one of the currently available non-invasive healing-enhancing devices besides electro-stimulation (pulsed electro-magnetic field, PEMF). This modality has been leveraged to enhance drug delivery, expedite injury recovery, improve muscle mobility, alleviate joint stiffness and muscle pain, and enhance bone fracture healing. Although LIPUS has been embraced within various medical disciplines, its integration into standard dental practices is still in its nascent stages, signifying an unexplored frontier with potentially transformative implications. Low-intensity pulsed ultrasound (LIPUS) has emerged as an attractive adjuvant therapy in various dental procedures, such as orthodontic treatment and maxillary sinus augmentation. Its appeal lies in its simplicity and non-invasive nature, positioning LIPUS as a promising avenue for clinical innovation. One particular area of interest is orthodontically induced inflammatory root resorption (OIIRR), an oftenunavoidable outcome of the orthodontic intervention, resulting in the permanent loss of root structure. Notably, OIIRR is the second most common form of root resorption (RR), surpassed only by root resorption related to pulpal infection. Given the high prevalence and potential long-term consequences of OIIRR, this literature review seeks to evaluate the efficacy of LIPUS as a therapeutic approach, with an emphasis on assessing its capacity to reduce the severity of OIIRR to a level of clinical significance. To conduct this systematic review, a comprehensive automated literature search was executed across multiple databases, including MEDLINE, Embase, PsycINFO, Web of Knowledge, Scopus, CINAHL, LILACS, SciELO, Cochrane, PubMed, trials registries, 3ie, and Google Scholar. Both forward and backward citation tracking was employed, encompassing studies published from database inception through January 2009 to April 2023. The review focused on randomized controlled trials (RCTs) that specifically evaluated the effects of low-intensity pulsed ultrasound therapy on orthodontically induced inflammatory root resorption (OIIRR), without restrictions of publication date. A stringent selection criterion was applied, and only studies demonstrating high levels of statistical significance were included. Ultimately, fourteen studies met the inclusion criteria and were subjected to further analysis. The overall quality of the included randomized controlled trials (RCTs) was rigorously assessed utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. This analysis revealed certain methodological limitations that posed challenges in drawing definitive conclusions from the available evidence. Despite these constraints, the review offers invaluable insights that can inform and guide future research. Specifically, it delineates recommendations for targeted populations, necessary interventions, appropriate outcome measures, suitable study designs, and essential infrastructure to facilitate further investigations. The synthesis of these insights aims to enhance the development and application of low-intensity pulsed ultrasound therapy within the field of dentistry, thereby contributing to improved patient outcomes.

Alignment efficiency and three-dimensional assessment of root resorption after alignment with conventional and copper-nickel-titanium archwires: A randomized controlled trial.

OBJECTIVE: To compare alignment efficiency and root resorption between nickel-titanium (NiTi) and copper-nickel-titanium (CuNiTi) archwires after complete alignment in mandibular anterior region. METHODS: In this two-arm parallel single-blind randomized controlled trial, forty-four patients with Class I malocclusion with mandibular anterior crowding were recruited form orthodontic clinic of All India Institute of Medical Sciences (Jodhpur, India). Patients were randomly allocated into NiTi and CuNiTi groups, with a 1:1 allocation. Alignment was performed using 0.014-in, 0.016-in, 0.018-in, 0.019x0.025-in archwire sequence in the respective groups, which terminated in 0.019 x 0.025-in stainless-steel working archwire. The primary outcome was alignment efficiency, measured on study models from baseline (T0) to the first, second, third, fourth and fifth-month (T5). Secondary outcome was root resorption, measured from CBCT scans taken at T0 and T5. Mixed-factorial ANOVA was used to compare Little's Irregularity Index (LII). For assessing the proportion of patients with complete alignment at the end of each month, Kaplan-Meier survival curve was built and time to treatment completion was compared between groups using log rank test. Paired t-test was used to assess external apical root resorption (EARR) within groups, whereas independent t-test was used to evaluate LII and EARR between the groups. RESULTS: Twenty-two patients were recruited in each group. One patient was lost to follow-up in the CuNiTi group. No statistically significant differences were observed in alignment efficiency between the groups (p>0.05). Intergroup comparison revealed that the changes in root measurement in three-dimensions were not statistically significant (p>0.05), except for mandibular right central incisor, which showed increased resorption at root apex in NiTi group (p<0.01). CONCLUSION: The two alignment archwires showed similar rate of alignment at all time points. Root resorption measurement did not differ between the NiTi and CuNiTi groups, except for the mandibular right central incisor, which showed more resorption in NiTi group.

Stem cells derived from human exfoliated deciduous teeth-based media in a rat root resorption model.

OBJECTIVE: Root resorption may occur during orthodontic treatment. Herein, we investigated the effect of a culture supernatant of stem cells derived from human exfoliated deciduous teeth on root resorption. DESIGN: Twelve 8-week-old male Sprague-Dawley rats were used, and their maxillary first molars were pulled with excessive orthodontic force to induce root resorption. On days 1 and 7 after traction initiation, stem cells derived from human exfoliated deciduous teeth and alpha minimum essential medium (control group) were administered. After 14 days, the maxillary bone was evaluated for tooth movement. The expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17 was evaluated on the compression side and tension side. RESULTS: No significant difference in tooth movement was observed between the two groups. Root resorption decreased in the group administered the culture supernatant compared with in the control. Immunohistochemical staining revealed increased osteoprotegerin expression and decreased receptor activators for nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17 on the compression side and tension side. CONCLUSIONS: Administration of stem cells derived from human exfoliated deciduous teeth affected the expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6 and interleukin 17; hence, these stem cells may inhibit root resorption by regulating their expression.

A case of radicular cyst on deciduous tooth in a 7-year-old child.

Radicular cysts are the most common cystic lesions in the oral cavity, and have a rare occurrence in the primary dentition. We report a case of radicular cyst of mandible in child by multimodal imaging including panoramic radiography, CT, and MR imaging. A 7-year-old girl presented with swelling and without pain, and hypoesthesia on the right side of the mandible. On clinical examination, an expansive lesion with undulation was found to the buccal cortex of the right side of the mandible. Panoramic radiograph showed a unilocular radiolucency with well-defined margin, displaced tooth, and root resorption in the right mandible. Regarding CT imaging, axial soft tissue algorithm CT and bone tissue algorithm CT showed a low-attenuation internal structure and expansion of the buccal cortex of the right side of the mandible. Three-dimensional-CT showed expansion of the buccal cortex of the right side of the mandible. Multiplanar reformation imaging showed displaced tooth, root resorption, and expansion of the buccal cortex of the right side of the mandible. On T1-weighted image, the expansive lesion showed low signal intensity, and T2-weighted and STIR images revealed high signal intensity. A partial biopsy of the mandibular region was performed. Histopathological diagnosis was radicular cyst caused by apical periodontitis with abscess. This case suggests that multimodal imaging, especially CT and MR imaging, could be effective for evaluating mandibular lesions in child.

Predictors of complications associated with unerupted maxillary canines: a cone beam computed tomography study.

To detect predictive factors for the occurrence of complications associated with unerupted maxillary canines (C). A total of 83 cone beam computed tomograms (CBCT), made from November 1, 2021 to October 31, 2022, have met the inclusion criteria, whereby 110 unerupted C were detected. Independent variables were: gender, age, and C position. Outcome variables were detected complications: external root resorption (ERR) and dilaceration of adjacent tooth, ERR and dilaceration of C, dentigerous cyst, canine ankylosis, and adjacent teeth malposition. Chi-square test and logistic regression analysis were used to examine the relationship between income variables and detected complications. Vertical position of unerupted C showed as predictor for adjacent tooth dilacerations and malposition. Chance for dilaceration increases 5.5-fold with C position at the middle third of lateral incisor (LI) root, while chance of malposition increases 23.4-fold with its supra-apical position to the LI root, in comparison to the C position occlusal to the LI cemento-enamel junction. Age is a predictive factor for dentigerous cysts, with decreasing the chance of their occurrence 1.5-fold with each additional year of age. Early evaluation of the vertical position and timely treatment of C are decisive steps in preventing complications.

Early-stage periodontal ligament compression predicts orthodontically induced root resorption in rats.

OBJECTIVES: To determine the effect of orthodontic pressure on periodontal ligament (PDL) compression in rats and assess correlation between PDL compression and orthodontically induced root resorption (OIRR). MATERIALS AND METHODS: Eight female Wistar rats aged 10 weeks underwent surgery to place 2 mini-screws at the center of the palatal plate. 25 cN coil springs connecting the maxillary first molars and mini-screws were applied bilaterally to generate mesial force. Maxillary first molars were assigned to undergo either bodily or tipping movements. Micro-computed tomography (µCT) scans were taken on days 0, 3, 7, and 14, and histological sections were taken on day 14. OIRR was measured from histological sections, and the corresponding PDL compression ratio was quantified using µCT images. RESULTS: The PDL was compressed by approximately 76% in tipping movement and 55% in bodily movement after 3 days, and by approximately 47% in bodily and tipping movements after 7 days of orthodontic force application. The extent of OIRR in tipping movement was significantly greater than that in bodily movement. A strong positive correlation between OIRR and PDL compression ratio was observed on day 3; however, no correlation was observed on day 7. CONCLUSIONS: A strong correlation between PDL compression ratio and OIRR was observed at an early stage after the application of orthodontic force regardless of the tooth movement type (bodily or tipping), implying the importance of early stage PDL compression in the induction of OIRR.

Clinicopathologic Profile and Surgical Modalities in Mandibular Ameloblastoma: A Descriptive Study.

BACKGROUND: Ameloblastoma is a benign neoplasm composed of epithelial tissue with invasive and infiltrative behavior at the local level and a high recurrence rate, with various histopathologic patterns and clinical forms. Approximately 85% of conventional ameloblastomas occur in the mandible, most often in the body, angle, and ascending ramus area. The treatment modalities include both conservative and radical treatments. Postoperative follow-up is most important in the treatment of ameloblastoma. AIMS AND OBJECTIVES: To describe the clinicopathologic profile of mandibular ameloblastoma in patients undergoing different surgical modalities. The primary objective was to describe the clinicopathologic profile and surgical management of mandibular ameloblastoma in patients aged ≥18 years, who had reported to a tertiary dental care center for follow-up during the study period. The secondary objective was to describe the distribution of comorbidities associated with different surgical modalities and reconstructive methods. SUBJECTS AND METHODS: A total of 34 patients with mandibular ameloblastoma who underwent various surgical modalities between 2011 and 2021 were studied. Information was collected using a predesigned proforma and statistically analyzed. RESULTS: Thirty-four review cases of ameloblastoma were included in the study. The patients were analyzed concerning age, sex, site, size, clinical presentation, radiographic pattern, histopathologic subtype, type of surgery, and associated comorbidities. Most cases of mandibular ameloblastoma involve the age of 16 to 55 years. The mean age of occurrence was found to be 35.5±13.2. A female preponderance, a tumor size range of 2 to 4 cm, a multicystic variant, involvement of the mandibular body in the premolar-molar area, root resorption, cortical perforation, and a follicular type of histopathologic pattern were the common presentations. Isolated anterior tumors restricted to the incisor/canine region were not found. The common surgical modalities undertaken were conservative methods such as enucleation, and chemical cauterization, and radical methods such as marginal mandibulectomy and segmental resection. Reconstruction using a titanium plate or free fibular graft was performed in the indicated cases. The common comorbidities included difficulty in chewing and loss of facial contour. Recurrence after surgical treatment was rare. Only 9% of cases developed a recurrence within 5 years. No recurrence was noted in cases treated with radical treatment, whereas 50% of cases treated with conservative methods showed recurrence. CONCLUSION: The age of occurrence, site, and size of the tumor, cortical perforation, root resorption, histopathologic type, and radiographic patterns are widely considered factors in devising a treatment plan for mandibular ameloblastoma. However, there may be rare instances where these tumors behave differently regardless of their innocuous clinicopathologic presentation. Surgical procedures such as segmental resection and marginal mandibulectomy were found to be promising for the eradication of the tumor, and prevention of recurrences and metastasis. However, conservative measures such as enucleation and chemical cauterization were fraught with an increased risk of tumor recurrence and metastasis. Future studies with a larger sample size should focus on the clinicopathologic characteristics of ameloblastoma to elucidate its varied behavior and develop newer and advanced treatment modalities that would provide better surgical and postsurgical outcomes in affected patients.

[Experimental study of subcutaneous adipose-derived stem cells inhibiting orthodontic root resorption].

Objective: To investigate the effect of human subcutaneous adipose-derived stem cells (hADSCs) local transplantation on orthodontically induced root resorption (OIRR) and provide theoretical and experimental basis for the clinical application of hADSCs to inhibit OIRR. Methods: Forty 8-week-old male Sprague Dawley rats were randomly divided into experimental group and control group, with 20 rats in each group, to establish the first molar mesial orthodontic tooth movement (OTM) model of rat right maxillary. The rats in the experimental group were injected with 25 µL of cell suspension containing 2.5×10 5 hADSCs on the 1st, 4th, 8th, and 12th day of modeling, while the rats in the control group were injected with 25 µL of PBS. The rat maxillary models were obtained before and after 7 and 14 days of force application, and 10 rats in each group were killed and sampled after 7 and 14 days of force application. The OTM distance was measured by stereomicroscope, the root morphology of the pressure side was observed by scanning electron microscope and the root resorption area ratio was measured. The root resorption and periodontal tissue remodeling of the pressure side were observed by HE staining and the root resorption index was calculated. The number of cementoclast and osteoclast in the periodontal tissue on the pressure side was counted by tartrate resistant acid phosphatase staining. Results: The TOM distance of both groups increased with the extension of the force application time, and there was no significant difference ( P<0.05). There was no significant difference in OTM distance between the experimental group and the control group after 7 and 14 days of force application ( P>0.05). Scanning electron microscope observation showed that small and shallow scattered resorption lacunae were observed on the root surface of the experimental group and the control group after 7 days of force application, and there was no significant difference in the root resorption area ratio between the two groups ( P>0.05); after 14 days of application, the root resorption lacunae deepened and became larger in both groups, and the root resorption area ratio in the experimental group was significantly lower than that in the control group ( P<0.05). The range and depth of root absorption in the experimental group were smaller and shallower than those in the control group, and the root absorption index in the experimental group was significantly lower than that in the control group after 14 days of force application ( P<0.05). The number of cementoclast in the experimental group was significantly lower than that in the control group after 7 and 14 days of force application ( P<0.05); the number of osteoclasts in the experimental group was significantly lower than that in the control group after 14 days of force application ( P<0.05). Conclusion: Local transplantation of hADSCs may reduce the area and depth of root resorption by reducing the number of cementoclasts and osteoclasts during OTM in rats, thereby inhibiting orthodontic-derived root resorption.

Effect of icariin surface treatment on the resorption of denuded roots after replantation in rat.

AIM: Limiting the incidence of resorption associated with delayed replantation of avulsed teeth is critical for long-term tooth survival. In this study, we assessed whether icariin, a natural product with anti-osteoclastic properties, could reduce root resorption in a rat model of tooth replantation. METHODOLOGY: Cytocompatibility of icariin (10, 20, 40 and 80 µM) was evaluated by CCK-8 proliferation assay in vitro, and an osteoclastogenesis assay was performed to evaluate the effect of icariin on the differentiation of rat bone marrow macrophages and human peripheral blood monocytes into tartrate-resistant acid phosphatase-stained (TRAP+ ) multinucleated giant cells (MNGCs). Differentiation of human periodontal ligament stem cells (hPDLSCs) treated with icariin (10 µM) was also evaluated at 5, 10 and 21 days of osteogenic induction. The first maxillary molars of five-week-old male Sprague-Dawley rats were extracted, denuded of PDL, then treated either with neutralized collagen solution (Carrier control) or icariin in collagen (3 µg/µL) before replantation into their sockets. The animals were euthanized 2 weeks post-surgery for micro-computed tomography (micro-CT) imaging and histological analyses. RESULTS: Icariin was cytocompatible and significantly reduced the differentiation of TRAP+ MNGCs in a dose-dependent manner compared to the control. Moreover, icariin enhanced alkaline phosphatase activity, expression of osteogenic marker genes and proteins, and calcium deposition in hPDLSCs. Micro-CT imaging of the replanted samples demonstrated a significantly higher volume of remaining roots in the icariin-treated group than in the control group. Histological analysis revealed a marked number of resorptive lacunae with TRAP activity in the control group, whereas icariin-treated samples showed signs of functional healing and reduced osteoclastic activity. CONCLUSIONS: Icariin was biocompatible and demonstrated potent anti-osteoclastic and pro-osteogenic properties that reduced resorption and promoted functional healing of denuded roots in a rat maxillary first molar model of replantation. These findings indicate that root surface treatment with icariin may be a clinically relevant and practical method for improving the retention and survival of teeth with compromised PDL after delayed replantation following traumatic avulsion.

The effect of impacted third molars on second molar external root resorption, a cross-sectional cone beam computed tomography study.

BACKGROUND: Third molars have the highest prevalence of impaction in teeth and can cause pathological damage on the adjacent second molars. This study aims to evaluate the effects of factors related to impacted third molars on external root resorption (ERR) in adjacent second molars using cone-beam computed tomography (CBCT). MATERIAL AND METHODS: In CBCTs, the effect of impacted third molars on the root surface of adjacent second molars was investigated. Inclusion criteria for subjects were being older than 16 and younger than 55, presence of at least one impacted third molar and adjacent second molar. Exclusion criteria were pathology, a follicle gap greater than 5 mm, crowned second molar, severe decay, an artifact on a radiologic image, and previous surgery on the second or third molars. The investigations were made based on age range, gender, tooth inclination, Pell-Gregory classification, retention type, contact area, root formation, pericoronal width, and tooth absence on the same quadrant for potential risk factors. The collected data were statistically analyzed with R software. The Chi-Square test was used to find out any significant difference. Logistic regression analyses were done for potential risk factors for ERR. RESULTS: A total of 437 impacted third molars and adjacent second molars were investigated using CBCT. Of these, 381 met the inclusion criteria. Mesioangular and horizontal inclination, Pell-Gregory Class B-C, contact area, and retention type were found the statistically potential risk factors for ERR. CONCLUSIONS: The impacted third molar with horizontal or mesioangular position, and osseous retention, with Pell and Gregory Class B and C, are more likely to cause external root resorption in adjacent second molars.

[Cone-beam CT imaging features of common cystic lesions associated with the impacted mandibular third molar].

Objective: To analyze the imaging features of cone-beam CT (CBCT) of ameloblastoma (AB), odontogenic keratocyst (OKC) and dentigerous cysts (DC) associated with the mandibular impacted third molars,so as to provide useful information for differential diagnosis of these lesions. Methods: The patients who were with complete clinical data, pathological diagnosis and CBCT images from AB, OKC and DC around the mandibular impacted third molars were collected in Peking University Hospital of Stomatology from August 2016 to December 2021. A total of 109 patients (14 were diagnosed as AB, 23 were diagnosed as OKC and the others were diagnosed as dental cysts) were collected, including 73 males and 36 females. The age ranged from 11 to 70. The analyzed imaging features included location and internal density of the lesions, bone expansion, root resorption of adjacent teeth and types of the impacted teeth. The Chi square test was used to compare the gender of different lesions, and the Fisher's exact test was used to compare imaging features of lesions. When P<0.05, there was a significant difference among the three. Logistic regression analysis was performed to determine the imaging features that significantly contribute to correct imaging diagnosis. Corresponding P-values were calculated for all factors from multivariate models. Results: In the 23 cases of OKC, no special location was observed for the center of the lesion, heterogeneous high-density were seen in 21.7% of the cases, 56.5% of the cases had no significant bone expansion and the impacted teeth were not specially oriented. Among the 14 AB, 7 cases (7/14) were mainly located in the ramus of the mandible, and all cases (14/14) had buccal/lingual expansion of the jaw, 8 cases (8/14) presented root resorption of the adjacent teeth, and mesial impacted mandibular third molar were seen in 6 cases (6/14). Among the 72 DC, 88.9% (64/72) of the cases were mainly limited to the crown of the impacted third molar, 72.2% (52/72) of the cases had no obvious bone expansion, inverted impacted teeth were shown in 56.9% (41/72) of the cases. There was a significant difference among the three groups (χ2=7.30, P=0.026) in gender. AB and odontogenic cyst were more common in men than in women, while the incidence of OKC was roughly equal between men and women.There were significant differences in the location (P<0.001), internal density (P=0.001) of the lesions, bone expansion (P<0.001) and types of the impacted teeth (P<0.001), while no statistical difference was found for root resorption of adjacent teeth (P=0.153). Logistics regression analysis showed that the location of the lesion, internal density, bone expansion, root resorption of adjacent teeth and the types of impacted teeth had significant effects on the accurate diagnosis of the three kinds of lesions. Conclusions: Location, internal density, bone expansion and types of the impacted teeth played an important role in the correct imaging diagnosis. Further analysis indicates that when the classification of impacted teeth and the location of lesions are considered synchronously, DC can be differentiated from AB and OKC.

Effectiveness of tubular coaxial nickel-titanium and copper nickel-titanium orthodontic aligning archwires: A randomized clinical trial.

BACKGROUND: This study aimed to compare tubular coaxial-NiTi and copper-NiTi orthodontic aligning archwires in terms of teeth alignment, patients' pain perception, and root resorption. SUBJECTS AND METHODS: Orthodontic patients aged 12 years or older, having Little's irregularity index (LII) of 5-9mm were randomly allocated to either the copper-NiTi group or tubular coaxial-NiTi group with a 1:1 allocation ratio. The archwire sequence was 0.014-inch followed by 0.018-inch for the copper-NiTi group and 0.016-inch followed by 0.018-inch for the tubular coaxial-NiTi group. Each archwire was left in place for eight weeks before progressing to the next size. Good quality impression for the lower arch before treatment (T0) and thereafter every 4 weeks up to 16 weeks was taken to measure LII. Evaluation of pain perception was performed using a visual analog scale (VAS) during the first week following each archwire insertion. Assessment of root resorption was undertaken at T0 and after 16 weeks by taking periapical radiographs for mandibular central incisors using the long cone paralleling technique. RESULTS: A total of 33 patients were randomized and selected for participation. Of those, 31 patients with a mean age of 15.45±2.22 who completed the trial were included in the analyses (15 patients in the copper-NiTi group and 16 patients in the tubular coaxial-NiTi group). In both groups, the irregularity index significantly decreased after 16 weeks of treatment with an overall reduction of 5.22mm for the copper-NiTi group and 6.03mm for the tubular coaxial-NiTi group. However, the difference between the two groups was not statistically significant. Likewise, pain perception and root resorption were not significantly different between the two study groups. CONCLUSIONS: Both copper-NiTi and tubular coaxial-NiTi archwires were equally effective in terms of teeth alignment, patients' pain perception, and root resorption. Consideration could be given to the cost and clinician preference when selecting an initial archwire. REGISTRATION: the trial was registered in ClinicalTrials.gov on 26/05/2022 with a registration ID: NCT05391542, https://clinicaltrials.gov/ct2/show/NCT05391542.

Orthodontic treatment in traumatized permanent teeth: a systematic review / Tratamento ortodôntico em dentes permanentes traumatizados: uma revisão sistemática

Objective: to analyze, through literature review, the available literature on orthodontic treatment in traumatized permanent teeth. Methods: A literature search was performed in electronic databases (PubMed and SciELO) using the descriptors [tooth injuries] OR [injuries, teeth] OR [injury, teeth] OR [teeth injury] OR [injuries, tooth] OR [injury, tooth] OR [tooth injury] OR [teeth injuries] AND [orthodontics]. Observational studies and clinical trials were included, narrative reviews, laboratory and in vitro studies, case reports and series as well as articles that presented abstracts written in languages other than Portuguese, English and Spanish were excluded from the study. Two reviewers considered the eligibility, the risk of bias of the analyzed data and the qualitative synthesis of the studies included. A total of 1,322 references were found and 4 articles met all inclusion criteria and were included in the qualitative analysis. Some consequences like pulp necrosis and root resorption have been highlighted and trauma severity should be considered when orthodontically intervening in previously traumatized teeth. Final considerations: The traumatized teeth can be orthodontically treated as long as the time of tissue reorganization is respected, and the pull and periodontal conditions are followed up.(AU)

Objetivos: analisar, por meio de revisão de literatura, a respeito do tratamento ortodôntico em dentes permanentes traumatizados. Metodologia: Uma pesquisa bibliográfica foi realizada em bancos de dados eletrônicos (PubMed e SciELO) usando os descritores [tooth injuries] ou [injuries, teeth] ou [injury, teeth] ou [teeth injury] ou [injuries, tooth] ou [injury, tooth] ou [tooth injury] ou [teeth injuries] e [orthodontics]. Foram incluídos estudos observacionais e ensaios clínicos, revisões narrativas, estudos laboratoriais e in vitro, relatos de casos e séries, bem como artigos que apresentassem resumos redigidos em idiomas diferentes do português, inglês e espanhol foram excluídos do estudo. Dois revisores consideraram a elegibilidade, o risco de viés dos dados analisados e a síntese qualitativa dos estudos incluídos. Foram encontradas 1.322 referências e 4 artigos atenderam a todos os critérios de inclusão e foram incluídos na análise qualitativa. Algumas consequências como necrose pulpar e reabsorção radicular têm sido destacadas e a gravidade do trauma deve ser considerada na intervenção ortodôntica em dentes previamente traumatizados. Considerações finais: Os estudos incluídos nesta revisão sugerem que dentes traumatizados podem ser tratados ortodônticamente desde que respeitado o tempo de reorganização tecidual e acompanhadas as condições pulpares e periodontais.(AU)

Periodontal Fibroblasts-Macrophage Crosstalk in External Inflammatory Root Resorption.

INTRODUCTION: This study aimed to understand the influence of periodontal fibroblasts (PDLFs) on clastic differentiation of macrophages (Mφ) in different resorptive environments. METHODS: PDLF-Mφ direct coculture (juxtacrine) was seeded on dentin, cementum, and polystyrene with/without lipopolysaccharide, macrophage colony-stimulating factor, and receptor activator of nuclear factor kappa beta ligand for 7 and 14 days and stained for tartrate-resistant acid phosphatase (TRAP) activity. PDLF-Mφ cocultured on polystyrene were immunostained for CD80, CD206, NFATc1, STAT6, and periostin, and cell culture supernatants were assessed for cytokines on days 2 and 7. Mφ grown in conditioned media of PDLFs (paracrine) and Mφ monoculture were used as controls. Data was analyzed using Student t test and one-way analysis of variance with the Tukey multiple comparisons test (P < .05). RESULTS: PDLF-Mφ coculture showed a higher number of TRAP-positive multinucleated cells than Mφ monoculture on dentin and polystyrene. No TRAP-positive multinucleated cells were observed in paracrine and cementum. The expression of CD80 and CD206 in PDLF-Mφ was similar at day 2, whereas CD206 was greater than CD80 at day 7. The expression of STAT6 was greater than NFATc1 at both days 2 and 7 (P < .05). Periostin expression in the presence of the lipopolysaccharide, macrophage colony-stimulating factor, and receptor activator of nuclear factor kappa beta ligand combination was down-regulated in PDLF monoculture, whereas it was up-regulated in PDLF-Mφ coculture. The cytokine profile of PDLF-Mφ on day 2 was predominated by interleukin (IL)-1ß, tumor necrosis factor alpha, and MMP9 and MMP2 on day 7. IL-6 and IL-8 showed steady expression at both days 2 and 7. CONCLUSIONS: The study highlights the juxtacrine effect of PDLFs on the clastic differentiation of Mφ with a difference in clastic activity between dentin and cementum. The study also emphasizes the temporal effect of tumor necrosis factor alpha, MMP2, MMP9, and IL-1ß on intercellular crosstalk in resorptive environments.