The effect of fibroblast growth factor-2 on the outcomes of tooth replantation: A systematic review of animal studies.

Background/Aim: The ideal treatment of tooth avulsion is replantation. However, replanting teeth may lead to root resorption. Fibroblast growth factor-2 (FGF-2) is a cytokine that plays an important role in wound repair and tissue regeneration. Recently, FGF-2 has been studied a potential regenerative agent to prevent root resorption and ankylosis. The aim of this review is to analyze and summarize the currently available literature focusing on using FGF-2 based regenerative modalities to improve the outcomes of tooth replantation. Materials and Methods: An electronic search was conducted via PubMed/Medline, Google Scholar and ISI Web of Knowledge, using the Medical Subject Headings (MeSH) terms "Basic fibroblast growth factor," "Fibroblast growth factor-2," "tooth replantation," and "replantation" for studies published between January 2001 and June 2021. Data was extracted and quality assessment was carried using the ARRIVE guidelines. Results: Nine animal studies were included in this review. In six studies, FGF-2 had a favorable effect on the tissue regeneration around roots of replanted teeth when compared to other treatment groups. However, quality assessment of the studies revealed many sources of bias and deficiencies in the studies. Conclusions: Within the limitations of this study, it may be concluded that FGF-2 may improve the outcomes of delayed replantation of avulsed teeth. However, more long-term animal studies, with improved experimental designs, and clinical trials are required to determine the clinical potential of the growth factor in improving the outcomes of delayed tooth replantation.

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.

Prevention and repair of orthodontically induced root resorption using ultrasound: a scoping review.

INTRODUCTION: This review summarizes the available recent literature on different mechanisms and parameters of pulsed ultrasound (US) that have been used during orthodontic treatments to prevent and repair root resorption. AREAS COVERED: A literature search was conducted between January (2002) and September (2022) in the following databases: PubMed, Google-Scholar, Embase, and The-Cochrane-Library. After exclusions, a total of 19 papers were included in the present review. The most used US parameters with positive outcomes were frequency of 1.5 MHz, pulse repetition frequency of 1000 Hz, output intensity of 30 mW/cm2, duration of application of 20 min and total number sessions were 14 with a repetition interval of 1 day. The suggested mechanisms induced by US were alteration of cementoblasts, osteoblasts, osteoclasts, alkaline-phosphatase (ALP), runt-related-gene-2 (Runx2), osteoprotegerin (OPG), type-I-collagen (Col-I), C-telopeptide-type-I-collagen (CTX-I), hepatocyte-growth-factor (HGF), bone morphogenetic protein-2 (BMP-2), cyclooxygenase-2 (Cox-2), calcium (Ca2+), receptor activator of nuclear factor-kappa-B ligand (RANKL), and receptor activator of nuclear factor-kappa-B (RANK). EXPERT OPINION: Understanding mechanisms and deciding which parameters of US that can be used during orthodontic treatment to prevent and repair root resorption is a great challenge. This work summarizes all the available data that can aid this process and suggest that US is an effective noninvasive method not only in prevention and repairing of orthodontic induced root resorption but also in accelerating teeth movement.

RANKL+ senescent cells under mechanical stress: a therapeutic target for orthodontic root resorption using senolytics.

In dentistry, orthodontic root resorption is a long-lasting issue with no effective treatment strategy, and its mechanisms, especially those related to senescent cells, remain largely unknown. Here, we used an orthodontic intrusion tooth movement model with an L-loop in rats to demonstrate that mechanical stress-induced senescent cells aggravate apical root resorption, which was prevented by administering senolytics (a dasatinib and quercetin cocktail). Our results indicated that cementoblasts and periodontal ligament cells underwent cellular senescence (p21+ or p16+) and strongly expressed receptor activator of nuclear factor-kappa B (RANKL) from day three, subsequently inducing tartrate-resistant acid phosphatase (TRAP)-positive odontoclasts and provoking apical root resorption. More p21+ senescent cells expressed RANKL than p16+ senescent cells. We observed only minor changes in the number of RANKL+ non-senescent cells, whereas RANKL+ senescent cells markedly increased from day seven. Intriguingly, we also found cathepsin K+p21+p16+ cells in the root resorption fossa, suggesting senescent odontoclasts. Oral administration of dasatinib and quercetin markedly reduced these senescent cells and TRAP+ cells, eventually alleviating root resorption. Altogether, these results unveil those aberrant stimuli in orthodontic intrusive tooth movement induced RANKL+ early senescent cells, which have a pivotal role in odontoclastogenesis and subsequent root resorption. These findings offer a new therapeutic target to prevent root resorption during orthodontic tooth movement.

RANKL+ senescent cells under mechanical stress: a therapeutic target for orthodontic root resorption using senolytics / 国际口腔科学杂志·英文版

In dentistry, orthodontic root resorption is a long-lasting issue with no effective treatment strategy, and its mechanisms, especially those related to senescent cells, remain largely unknown. Here, we used an orthodontic intrusion tooth movement model with an L-loop in rats to demonstrate that mechanical stress-induced senescent cells aggravate apical root resorption, which was prevented by administering senolytics (a dasatinib and quercetin cocktail). Our results indicated that cementoblasts and periodontal ligament cells underwent cellular senescence (p21+ or p16+) and strongly expressed receptor activator of nuclear factor-kappa B (RANKL) from day three, subsequently inducing tartrate-resistant acid phosphatase (TRAP)-positive odontoclasts and provoking apical root resorption. More p21+ senescent cells expressed RANKL than p16+ senescent cells. We observed only minor changes in the number of RANKL+ non-senescent cells, whereas RANKL+ senescent cells markedly increased from day seven. Intriguingly, we also found cathepsin K+p21+p16+ cells in the root resorption fossa, suggesting senescent odontoclasts. Oral administration of dasatinib and quercetin markedly reduced these senescent cells and TRAP+ cells, eventually alleviating root resorption. Altogether, these results unveil those aberrant stimuli in orthodontic intrusive tooth movement induced RANKL+ early senescent cells, which have a pivotal role in odontoclastogenesis and subsequent root resorption. These findings offer a new therapeutic target to prevent root resorption during orthodontic tooth movement.

Npp1 prevents external tooth root resorption by regulation of cervical cementum integrity.

Tooth roots embedded in the alveolar bone do not typically undergo resorption while the bone continues remodeling in its physiological state. In this study, we analyzed genetically modified mice with the functional inactivation of nucleotide pyrophosphatase 1 (Npp1), encoded by ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1). This mutation leads to the formation of ectopic cervical cementum vulnerable to external tooth root resorption. Cementoblasts with the inactivation of Enpp1 extensively expressed non-collagenous matrix proteins enriched with bone sialoprotein (Bsp), dentin matrix protein 1 (Dmp1), and osteopontin (Opn), which have roles in mineralization through nucleation and in cell adhesion through the Arg-Gly-Asp (RGD) motif. In cementoblasts with the inactivation of Enpp1, ß-catenin was significantly activated and induced the expression of these non-collagenous matrix proteins. In addition, adenosine triphosphate (ATP), which is the most preferred substrate of Npp1, accumulated extracellularly and autocrinally induced the expression of the receptor activator of nuclear factor κB ligand (Rankl) in cementoblasts with inactivated Npp1. Consequently, these results strongly suggest that functional Npp1 preserves cervical cementum integrity and supports the anti-resorptive properties of tooth roots through ATP homeostasis in the physiological state of cervical cementum.

[Effects of human periodontal ligament fibroblast-derived exosomes on reducing rat root resorption after delayed tooth replantation].

PURPOSE: To explore the effect of healthy human periodontal ligament fibroblasts (hPDLFs) -derived exosomes on tooth resorption after delayed tooth replantation in rats and its possible mechanism. METHODS: The exosomes derived from hPDLFs were isolated and identified in thirty six-week-old SD rats and randomly divided into control group and exosome group. The right maxillary first molar was extracted to establish a delayed tooth replantation model. The dislocated teeth were implanted back into the alveolar fossa after 30 minutes. 40 µL Hanks' balanced salt solution (HBSS) were injected into the periodontal tissue, and the experimental group was injected with 40 µL HBSS containing exosomes. The rats were sacrificed at 1, 2, and 4 weeks. Hematoxylin-eosin (H-E) staining was used to observe tooth resorption. Tartrate-resistant acid phosphatase(TRAP) staining was used to observe the number of osteoclasts. The expression of osteoprotegerin(OPG) in periodontal ligament was detected by immunohistochemical staining. The differences in distribution of each genotype were analyzed with SPSS 17.0 software package. RESULTS: The identification experiment showed that extracellular vesicles were exosomes. hPDLFs-derived exosomes inhibited root resorption after delayed tooth replantation, reduced the expression of TRAP-positive osteoclasts (P＜0.05), and promoted expression of OPG in periodontal ligament (P＜0.05). CONCLUSIONS: After delayed tooth replantation, PDLFs-derived exosomes reduce the number of osteoclasts, promote OPG expression in the periodontal ligament, and reduce tooth root resorption after replantation.

Canines and inflammatory external apical resorption in healthy maxillary lateral incisors due to occlusal trauma: when to detect the position of maxillary canines, to prevent it?

JUSTIFICATION: Canines represent corners in the dental arch, and are important features in facial esthetics, as they support the upper lip, wing of the nose, and influence the nasolabial fold and the appearance of facial aging. In the laterality movements, the canines guidance coordinate the opening and closing of the teeth, saving the TMJ from sudden movements. DISCUSSION: As a result of the lack of eruption or the inadequate positioning of the maxillary canine, the loss of the laterality guide may occur, which will then occur in the maxillary lateral incisor, inducing lesions of "occlusal trauma", such as inflammatory root resorption. Likewise, without well positioned canines, there may be premature aging and change in facial esthetics. CONCLUSION: In order to avoid problems with eruption and positioning of the maxillary canines, early diagnosis is made by analyzing their position and their relationship with the other teeth, and in the three-dimensional context of the maxilla, between 8-10 years of age. Preventive measures can create bone space and direction so that the maxillary canines can occupy their position in the dental arch.

Physical properties of root cementum: Part 28. Effects of high and low water fluoridation on orthodontic root resorption: A microcomputed tomography study.

INTRODUCTION: Transient inflammatory surface resorption, referred to as orthodontic induced inflammatory root resorption (OIIRR), is an iatrogenic consequence of orthodontic tooth movement. Systemic fluoride has been associated with a reduction of OIIRR. This study aimed to investigate the effects of water fluoridation levels on OIIRR in a clinically applicable human orthodontic model. METHODS: Twenty-eight patients who required bilateral maxillary first premolar extraction as part of orthodontic treatment were selected from 2 cities with high and low water fluoridation of ≥2 ppm and ≤0.05 ppm, respectively. Patients were separated into high fluoride (HF) and low fluoride (LF) groups on the basis of water fluoridation levels. Bilateral maxillary first premolar teeth were subjected to 150 g of buccal tipping forces for 12 weeks with reactivation every 4 weeks. Teeth were extracted at the end of 12 weeks. Root resorption crater volume was determined using microcomputed tomography and 3-dimensional reconstruction. RESULTS: HF group showed significantly less mean root resorption volume on the palatal root surface when compared with the LF group (P = 0.025). This difference was specifically displayed at palatal apical regions (P = 0.041). When root resorption volumes from the zones of orthodontic pressure (buccal cervical, palatal apical) were combined, the mean difference between HF and LF groups was statistically significant (P = 0.045). CONCLUSIONS: Findings of the present study indicated a positive correlation between water fluoridation and the reduction of OIIRR, especially at the zones of orthodontic pressure, using a clinically relevant human orthodontic model.

Evaluation of pH and calcium ion release at the simulated external root resorption cavities of teeth obturated with bioceramic sealer.

OBJECTIVE: The purpose of this study was to evaluate pH and calcium ion release at the outer dentin surface of simulated external root resorption cavities after root canals obturated with bioceramic root canal sealer compared with those medicated with calcium hydroxide. MATERIALS AND METHODS: Sixty extracted human single-rooted teeth were selected and instrumented. External root resorption cavities were prepared at the lingual surface of the root. The teeth were randomly divided into three groups: (1) Bioceramic sealer group, canals were obturated with gutta-percha and BioRoot sealer; (2) Calcium hydroxide group, canals were medicated with UltraCal XS; (3) Control group, canals were left empty. Thirty specimens were used for evaluation of pH at 7, 14, and 28 days (n = 10 per group) and the other 30 specimens were used for evaluation of calcium ion diffusion at 28 days (n = 10 per group). RESULTS: Calcium hydroxide group showed the highest median pH value at all time points (7, 14, and 28 days). Both calcium hydroxide and bioceramic sealer groups showed significantly higher median pH values compared with control (p < .001). Comparing within groups, both bioceramic sealer group and calcium hydroxide group showed significantly decreased median pH over time, while the median pH of the control did not show any significant difference among Days 7, 14, and 28. Both calcium hydroxide and bioceramic sealer groups had significantly higher calcium ion release than control. Notably, bioceramic sealer group showed significantly higher calcium ion release than the calcium hydroxide group (p < .01). CONCLUSIONS: Root canals obturated with gutta-percha and bioceramic sealer showed high calcium ion levels at the simulated external root resorption cavities but did not show an extended period of alkaline pH.

Lithium reduces orthodontically induced root resorption by suppressing cell death, hyalinization, and odontoclast formation in rats.

OBJECTIVES: To examine whether lithium suppresses orthodontically induced root resorption (OIRR) via two mechanisms (prevention of hyalinization in periodontal tissue and suppression of odontoclasts) and to investigate the changes in the periodontal tissue and alveolar bone, focusing on the appearance of cell death, hyalinization, and odontoclasts. MATERIALS AND METHODS: The maxillary first molars of 10-week-old male Wistar rats were moved mesially by a closed-coil spring for 14 days. Lithium chloride (LiCl; 0.64 mM/kg) or saline (control) was administered intraperitoneally daily. Tooth movements were measured using micro-computed tomography. Appearances of cell death, hyalinization, and odontoclasts were evaluated by histological analysis. RESULTS: OIRR observed on day 14 in the control group was suppressed strongly by LiCl administration. Apoptotic cells observed on day 1 in the compression area were gradually diminished on days 2 and 3 and transformed to hyalinization tissue in the control group. LiCl administration remarkably suppressed this cell death and subsequent hyalinization. Also, the appearance of odontoclasts in the compression area observed on day 7 was significantly suppressed by LiCl administration. Accordingly, these degenerative processes to OIRR were suppressed substantially by LiCl treatment. CONCLUSIONS: Lithium reduces OIRR through the suppression of periodontal ligament cell death, hyalinization, and odontoclast formation.

Management of internal and external root resorption in primary teeth of a 3-year-old with myelomeningocele: A case report.

BACKGROUND: Myelomeningocele (MMC) is a severe manifestation of spina bifida. Children with MMC have motor disability, hydrocephalus, skeletal abnormalities, and mental retardation. These individuals are more susceptible to caries due to poor oral hygiene, carbohydrate-rich diet, prolonged use of sugar-containing medications and limited motor abilities. Latex allergy is an important factor to be considered during the dental rehabilitation of such patients. CASE REPORT: A 3-year-old girl visited the dental clinic with the chief complaint of multiple carious teeth and H/o neural tube defect (NTD) which had been operated on at the age of 6 weeks. On dental examination, multiple dental abscesses and severe early childhood caries were noted. Radiographic evaluation revealed internal root resorption of tooth "K" and external root resorption of tooth "T." The two teeth were treated with ledermix paste followed by obturation with Vitapex® (Diadent Group International Inc., Burnaby, BC, Canada) along with triple antibiotic paste and placement of stainless steel crown (SSC). A latex-free environment was maintained during the entire treatment to prevent allergic reaction. A follow up after 42 months indicated clinical and radiographical success. CONCLUSION: The paper reports succesfull management of internal and external root resorption as well as latex allergy in a dental operatory. The dental perspective while dealing with patients having NTD is limited. Explaining the particulars of the treatment plan will aid in management of such cases .

Cell-Based Therapy for Tooth Replantation Following Avulsion: A Systematic Review.

The management of avulsed teeth undergoing delayed replantation remains a clinical challenge as there are currently no effective interventions that can improve periodontal healing and prevent replacement root resorption. While several preclinical studies have reported varied success using cell-based tissue engineering to improve periodontal healing, a consensus is required before further clinical translation. Therefore, this systematic review seeks to evaluate the efficacy of cell-based therapy in promoting periodontal healing following delayed replantation in animal models. MEDLINE (PubMed) and Embase were searched on September 27, 2020. Ten studies involving rodent and dog models met the inclusion criteria. Cell sources included gingiva, periodontal ligament (PDL), bone marrow, and adipose tissues. Generally, cell-based therapy had increased the proportion of root surfaces displaying periodontal healing and concomitantly reduced the proportion presenting with replacement root resorption and ankylosis. The best outcomes were observed following treatment with PDL-derived cells of various potency. Future preclinical studies will benefit from adopting measures to minimize bias during the conduct of animal experiments and the standardization of the outcome measures reporting. This will facilitate future reviews with possible pooling of results in the form of meta-analyses, allowing a consensus to be obtained from the literature. In addition, further research will be required to shed light on the implications of using allogeneic cells as well as the optimization of cell delivery protocols. The findings of this systematic review demonstrated the therapeutic potential of certain cell-based therapies in promoting periodontal healing following delayed replantation, thus highlighting their prospective clinical benefits and translational value. Impact statement Current therapies cannot predictably promote periodontal healing following delayed replantation of an avulsed tooth, especially when there is already significant root surface damage. This review systematically assessed the literature for preclinical studies employing cell-based therapies to promote periodontal healing following delayed replantation. The results showed that certain cell-based therapies significantly increased the formation of new periodontal ligament and reduced adverse healing outcomes of replacement root resorption and ankylosis. This highlights the potential clinical benefits and translational value of cell-based therapy for the replantation of avulsed teeth.

Nuclear factor-kappa B decoy oligodeoxynucleotide-loaded poly lactic-co-glycolic acid nanospheres promote periodontal tissue healing after tooth replantation in rats.

BACKGROUND: Excessive inflammation in the periodontal tissue after tooth replantation can lead to inflammatory root resorption and interrupt periodontal tissue regeneration. We tested the hypothesis that nuclear factor-κB decoy oligodeoxynucleotide-loaded poly lactic-co-glycolic acid nanospheres (NF-PLGA) inhibit excessive inflammation and promote healing of periodontal tissue after replantation in rats. METHODS: The upper right incisors of rats were extracted, immersed in different specific solutions, and replanted. The rats were euthanized at 7, 14, and 28 days after replantation. Morphological evaluation with micro-CT and histological assessment with hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP) staining was performed. Additionally, we examined the expression of interleukin (IL)-1ß, IL-6, transforming growth factor-ß1 (TGF-ß1), and fibroblast growth factor-2 (FGF-2) in the periodontal ligament (PDL) by performing immunohistological assessment. RESULTS: The NF-PLGA group showed significantly greater dental root thickness than the other experimental groups. Root resorption was not observed after the application of NF-PLGA on day 7. The application of NF-PLGA also resulted in a significantly lower number of TRAP-positive osteoclasts on days 7 and 14 after replantation. Significantly lower expression of IL-1ß and IL-6 and higher expression of TGF-ß1 and FGF-2 were observed under the application of NF-PLGA in the PDL. CONCLUSIONS: NF-PLGA promoted the healing process by inhibiting the initial excessive inflammatory response in the PDL, preventing root resorption, and promoting periodontal tissue regeneration. The findings also suggested that the PLGA nanospheres-mediated transfection of the decoy oligodeoxynucleotides can be useful for the clinical application of replanted tooth root surfaces.

Periodontal ligament repair after active splinting of replanted dogs' teeth.

BACKGROUND/AIM: The high rate of root resorption resulting from tooth replantation represents a serious clinical problem. In order to prevent ankylosis and replacement resorption, the contemporary literature highlights the importance of using a flexible stabilization for traumatized teeth. For this purpose, orthodontic devices may be promising for obtaining a better prognosis and periodontal repair. The aim of this study was to evaluate the effect of an active splinting protocol with controlled force in dog's teeth following replantation. MATERIAL AND METHODS: Sixty premolar roots from three dogs were used. They were submitted to endodontic treatment, hemisected, atraumatically extracted and subsequently replanted. They were divided into four groups: Passive Stabilization (n = 20)-after 20 min in a dry medium; Active Stabilization (n = 20)-after 20 min in a dry medium; Negative control (n = 10)-immediate replantation and passive Stabilization; and Positive control (n = 10)-90 min of extra-alveolar time and passive Stabilization. The samples were collected and submitted to histologic processing. They were then evaluated for the count of inflammatory cells, expression of neurotrophin 4, osteoclasts, apoptotic cells and collagen fibres. The results were submitted to ANOVA or Kruskal-Wallis statistical tests followed by Tukey or Dunn post-tests (α = 5%). RESULTS: Passive Stabilization with orthodontic brackets without traction used after replantation had the highest number of inflammatory cells (p = .0122), osteoclasts (p = .0013) and percentage of collagen fibres in the periodontal ligament (p < .0001) when compared to Active Stabilization with orthodontic brackets applying amild tensile force. Neurotrophin 4 had no statistically significant difference (p = .05), regardless of the treatment. The apoptotic cells count revealed statistical differences (p < .0001) between Active Stabilization (189.70 ± 47.99) and Positive Control (198.90 ± 88.92) when compared to Passive Stabilization (21.19 ± 32.94). CONCLUSION: The active splinting protocol using orthodontic appliances generating a light and controlled force favoured periodontal ligament repair of replanted teeth.

Three-dimensional evaluation of the effects of injectable platelet rich fibrin (i-PRF) on alveolar bone and root length during orthodontic treatment: a randomized split mouth trial.

BACKGROUND: The role of injectable platelet rich fibrin (i-PRF) in orthodontic treatment has not been investigated with focus on its effect on dental and bony periodontal elements. OBJECTIVE: To evaluate the efficacy of i-PRF in bone preservation and prevention of root resorption. METHODS: A randomized split-mouth controlled trial included 21 patients aged 16-28 years (20.85 ± 3.85), who were treated for Class II malocclusion with the extraction of the maxillary first premolars. Right and left sides were randomly allocated to either experimental treated with i-PRF or control sides. After the leveling and alignment phase, the canines were retracted with 150gm forces. The i-PRF was prepared from the blood of each patient following a precise protocol, then injected immediately before canine retraction on the buccal and palatal aspects of the extraction sites. Localized maxillary cone beam computed tomography scans were taken before and after canine retraction to measure alveolar bone height and thickness and canine root length (indicative of root resorption), and the presence of dehiscence and fenestration. Paired sample t-tests and Wilcoxon signed rank tests were used to compare the changes between groups. RESULTS: No statistically significant differences in bone height, bone thickness were found between sides and between pre- and post-retraction period. However, root length was reduced post retraction but did not differ between sides. In both groups, postoperative dehiscence was observed buccally and palatally and fenestrations were recorded on only the buccal aspect. CONCLUSIONS: I-PRF did not affect bone quality during canine retraction or prevent canine root resorption. I-PRF did not reduce the prevalence of dehiscence and fenestration. Trial registration ClinicalTrials.gov (identifier number: NCT03399760. 16/01/2018).

Notch signaling inhibition protects against root resorption in experimental immature tooth movement in rats.

INTRODUCTION: This study aimed to build an experimental immature tooth movement model and verify less resorption of incompletely developed roots than those fully developed during the same orthodontic treatment, followed by investigating the cellular and molecular mechanism. METHODS: The development of Wistar rat tooth was investigated using in vivo microcomputed tomography and hematoxylin and eosin staining to decide the optimal ages of rats for immature tooth and mature tooth groups. The rats in the immature tooth and mature tooth groups were divided into experimental, sham control, and blank control groups. After orthodontic treatment for 3 weeks, the mesial root volume, crown movement distance, neck movement distance, root inclination, and apical distance were measured by microcomputed tomography. The expressions of TRAP, Jagged1, Notch2, IL-6, and RANKL were analyzed by immunohistochemical staining and real-time polymerase chain reaction. The repair of root resorption was also investigated after removing orthodontic force for 3 and 6 weeks. RESULTS: The root achieved the development stage around 10 weeks, so 4-week-old rats and 10-week-old rats were used in the immature tooth group and mature tooth group, respectively. The volume of root resorption in the experimental immature tooth group was 0.0869 ± 0.0244 mm3, which was less than that in the mature tooth group (0.1218 ± 0.0123 mm3) (P <0.001). Immature tooth movement decreased TRAP-positive odontoclasts on the compression side while having no statistically significant effect on osteoclasts. The protein expression of Jagged1, Notch2, IL-6, and RANKL in the mature tooth group increased significantly compared with the immature tooth group, not only on the compression side but also on the tension sides. The mRNA expression of Jagged1, Notch2, and RANKL was significantly lower in the immature tooth group, whereas the expression of IL-6 had no significance but a strong tendency. The root volume after repairing for 3 weeks was still less than that of blank control, whereas after repairing for 6 weeks, the difference was not statistically significant. CONCLUSIONS: The experimental immature tooth movement model for the Wistar rat was achieved for the first time. The immature tooth will suffer less root resorption than the mature tooth, which may be due to odontoclastogenesis inhibition by decreased expression of Jagged1/Notch2/IL-6/RANKL signaling.

Effect of root surface treatment with denusomab after delayed tooth replantation.

OBJECTIVES: To evaluate denosumab, a human monoclonal antibody that mimics the effects of osteoprotegerin in bone metabolism, as a topical treatment of root surface to be used prior to delayed tooth replantation. MATERIALS AND METHODS: Thirty-six rats' right incisors were used. Teeth were extracted and divided into: delayed replantation without root surface treatment (control); delayed replantation with root surface treatment with denosumab 60 mg/mL and 30 mg/mL, respectively, for 10 min both experimentals groups. After that, the root canals were filled with calcium hydroxide and replanted. After 15 and 60 days, the animals were euthanized, and the samples were collected and processed for microscopic analysis. Histological sections were performed, and stained with HE to describe the dental characteristics, measure ankylosis, replacement resorption, and dental resorption by conventional microscopy. Also, was performed Brown & Brenn staining and immunohistochemistry for RANKL, OPG, and periostin. RESULTS: Denosumab 60 mg/mL reducted ankylosis (p < 0.0001), replacement resorption (p < 0.0001), and tooth resorption, 60 days after replantation, compared to untreated replanted teeth (p < 0.005). Lower bacterial contamination in root surface in the denosumab treatment groups was found, regardless of the concentration used (p < 0.001). Also, denosumab treatment inhibited the expression of RANKL without modulating OPG. Periostin was observed in periodontal ligament of replanted tooth, although this labelling was absent in the ankylosis areas, in both experimental periods. CONCLUSION: Treatment of the root surface with denosumab at 60 mg/mL of rat teeth before delayed replantation reduced dental root resorption compared with the untreated teeth after 60 days. CLINICAL RELEVANCE: Survival of a replanted tooth has been a challenge in clinical practice. The use of a medication, such as denosumab, to limit dental root resorption represents an important therapeutical approach.

Influence of thyroxine supplementation on orthodontically induced tooth movement and/or inflammatory root resorption: A systematic review.

The role of thyroxine administration on orthodontically induced tooth movement and/or inflammatory root resorption remains unclear. The aim was to assess the influence of thyroxine administration on orthodontically induced tooth movement and/or inflammatory root resorption. The study protocol was registered in PROSPERO (CRD42020164151). An electronic search of indexed databases was conducted without time or language restrictions up to and including May 2020. The following eligibility criteria were imposed: (a) original prospective controlled clinical studies and/or experimental studies on animal models; (b) subjects undergoing orthodontic therapy with fixed appliances; (c) presence of a control group [orthodontic tooth movement without thyroxine administration]; and (d) intervention: orthodontic tooth movement with thyroxine administration. Review articles, commentaries, letters to the editor, case reports/series, studies with no control group, cross-sectional studies, retrospective studies and studies where thyroxine was administered along with other interventions such as calcitonin and prostaglandins were excluded. Quality of available evidence and risk of bias within studies were assessed. Any disagreements were resolved via consensus discussions. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 8 animal studies were included. Four studies reported that thyroxine administration increases the rate of orthodontic tooth movement; 3 studies did not show a significant difference. Three studies showed that thyroxine administration decreases orthodontically induced inflammatory root resorption; 2 studies found no significant difference. The risk of bias among studies was high. In conclusion, the influence of thyroxine administration on orthodontic tooth movement and/or orthodontically induced inflammatory root resorption in animal models remains unclear.

Estrogen protects dental roots from orthodontic-induced inflammatory resorption.

OBJECTIVE: Root resorption is a side effect of orthodontic tooth movement (OTM). Despite the recognized role of estrogen on bone, there is little information about their effects on orthodontic-induced inflammatory root resorption (OIIRR). We aimed to investigate if estrogen deficiency affects OIIRR in two mice strains. METHODS: Female Balb/C (Balb) and C57BL6/J (C57) mice were ovariectomized (OVX) and replaced with estradiol (E2). Tooth samples subjected or not to OTM were collected and analyzed by microCT, histomorphometry and qPCR. RESULTS: OVX resulted in decreased root volume (RV/TV) and root mineral density (RMD) in Balb mice without OTM. In contrast, OVX did not modify physiological root structure of C57 mice. OTM and OIIRR were increased after OVX in both mice strains after 30 days. E2 replacement reversed this phenotype in Balb, but not in C57 mice. Due to the significant increase of OIIRR in OVX Balb mice, the expression of key molecules was investigated in periodontium. Accordingly, these mice showed increased expression of receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor alpha, matrix metalloproteinases-2 and -13 and decreased osteoprotegerin (OPG) and interleukin-10 expression after OTM. E2 replacement reversed the changes of these markers. CONCLUSION: The lack of estrogen in Balb mice without OTM triggered loss of root structure which was positively correlated to RANKL/OPG ratio. Regardless of mouse strain, the absence of estrogen following OTM induced OIIRR. Mechanisms involve the imbalance of RANKL/OPG system, inflammatory and osteoclastic makers.