Alveolar Bone Remodeling Research Articles

The Pivotal Role of Transient Receptor Potential Channels in Oral Physiology.

Transient Receptor Potential (TRP) Channels constitute a large family of non-selective permeable ion channels involved in the perception of environmental stimuli with a central and continuously expanding role in oral tissue homeostasis. Recent studies indicate the regulatory role of TRPs in pulp physiology, oral mucosa sensation, dental pain nociception and salivary gland secretion. This review provides an update on the diverse functions of TRP channels in the physiology of the oral cavity, with emphasis on their cellular location, the underlying molecular mechanisms and clinical significance. A structured search of bibliographic databases (PubMed and MEDLINE) was performed for peer-reviewed studies on the function of TRP channels on oral cavity physiology in the last ten years. A qualitative content analysis was performed of screened papers and a critical discussion on the main findings is provided. TRPs expression has been detected in major cell types of the oral cavity, including odontoblasts, periodontal ligament, oral epithelial, salivary gland cells, and chondrocytes of temporomandibular joints, where they mediate signal perception and transduction of mechanical, thermal, and osmotic stimuli. They contribute to pulp physiology through dentin formation, mineralization, and periodontal ligament formation, along with alveolar bone remodeling in the dental pulp and periodontal ligament cells. TRPs are also involved in oral mucosa sensation, dental pain nociception, saliva secretion, swallowing reflex and temporomandibular joints' development. Various TRP channels regulate oral cavity homeostasis, playing an important role in the transduction of external stimuli to intracellular signals in a cell typespecific manner and presenting promising drug targets for the development of pharmacological strategies to manage oral diseases.

Study of Alveolar Bone Remodeling Using Deciduous Tooth Stem Cells and Hydroxyapatite by Vascular Endothelial Growth Factor Enhancement and Inhibition of Matrix Metalloproteinase-8 Expression in vivo.

BackgroundPeriodontitis progression is characterized by alveolar bone loss, and its prevention is a major clinical problem in periodontal disease management. Matrix metalloproteinase-8 (MMP-8) has been shown to adequately monitor the treatment of chronic periodontitis patients as gingival crevicular fluid MMP-8s were positively associated with the severity of periodontal disease. Moreover, modulating the vascular endothelial growth factor (VEGF) levels in bones could be a good way to improve bone regeneration and cure periodontitis as VEGF promotes endothelial cell proliferation, proteolytic enzyme release, chemotaxis, and migration; all of which are required for angiogenesis.PurposeThe aim of this study was to determine the effect of hydroxyapatite incorporated with stem cells from exfoliated deciduous teeth (SHED) in Wistar rats’ initial alveolar bone remodeling based on the findings of MMP-8 and VEGF expressions.MethodsA hydroxyapatite scaffold (HAS) in conjunction with SHED was transplanted into animal models with alveolar mandibular defects. A total of 10 Wistar rats (Rattus norvegicus) were divided into two groups: HAS and HAS + SHED. Immunohistochemistry staining was performed after 7 days to facilitate the examination of MMP-8 and VEGF expressions.ResultsThe independent t-test found significant downregulation of MMP-8 and upregulation VEGF expressions in groups transplanted with HAS in conjunction with SHED compared with the HAS group (p < 0.05).ConclusionThe combination of SHED with HAS on alveolar bone defects may contribute to initial alveolar bone remodeling as evident through the assessments of MMP-8 and VEGF expressions.

Alveolar bone thickness and height changes following incisor retraction treatment with microimplants.

To evaluate alveolar bone remodeling following incisor retraction treatment with microimplants and to examine the relationship between crown/root distal movement and thickness/height changes of the alveolus. A total of 24 patients (mean age, 19.29 ± 4.64 years) with bialveolar protrusion treated by incisor retraction with microimplants were included. The distances of the crown and root tip movements as well as the thickness (alveolar bone thickness [ABT]; labial, lingual, and total) and vertical level (vertical bone level [VBL]; labial and lingual) of the alveolar bone were assessed using cone-beam computed tomography images obtained before treatment (T1) and after treatment (T2). All T1 and T2 variables were compared, and further comparisons of alveolar bone changes were conducted between the two groups based on the distance of the crown (low-crown-movement and high-crown-movement groups) and root movements (low-root-movement and high-root-movement groups). To determine the correlation of the crown or root movement with the variables of alveolar bone changes, Pearson correlation coefficients were calculated. Significant differences were found in all VBL and ABT variables after treatment in both jaws but not in total ABT. Based on the crown and root movements, alveolar bone change significantly differed between the root-movement groups, whereas there was no significant difference between the crown-movement groups. In addition, root movement showed significant correlations with the variables. Remarkable changes in the height and thickness of alveolar bone were found after microimplant-aided incisor retraction treatment in all groups except for total ABT. Root movement was significantly correlated with the alveolar bone changes.

Effects of anti-mouse RANKL antibody on orthodontic tooth movement in mice

Background/purposeOrthodontic tooth movement is achieved by alveolar bone remodeling, and therefore the balance of bone resorption and formation is important. Receptor activator of nuclear factor-κB ligand (RANKL) plays a crucial role in bone resorption. We previously reported that tumor necrosis factor-α (TNF-α) is also important in bone resorption during tooth movement. In this study, we focused on bone and root resorption during orthodontic tooth movement in mice using anti-mouse RANKL antibody (anti-mRANKL ab). Materials and methodsAnti-mRANKL ab was administered intraperitoneally to mice that subsequently underwent orthodontic tooth movement. After 10 days, tissues around the moved teeth were histologically evaluated. To confirm the effects of anti-mRANKL ab on TNF-α induced bone resorption, TNF-α was administered with and without anti-mRANKL ab into the supracalvaria and the sutures of the calvaria were histologically evaluated. ResultsOrthodontic tooth movement was suppressed in mice treated with anti-mRANKL ab. Root resorption was observed after orthodontic tooth movement, but not in mice treated with anti-mRANKL ab. In the calvarial experiment, the number of TRAP-positive cells in the calvarial sutures was lower in mice administered TNF-α with anti-mRANKL ab than in mice administered TNF-α alone. ConclusionOur findings suggest that anti-mRANKL ab suppressed orthodontic tooth movement. This needs to be considered when orthodontic tooth movement is required in patients using anti-RANKL antibody.

The minipig intraoral dental implant model: A systematic review and meta-analysis.

ObjectivesThe objective of this report was to provide a review of the minipig intraoral dental implant model including a meta-analysis to estimate osseointegration and crestal bone remodeling.MethodsA systematic review including PubMed and EMBASE databases through June 2021 was conducted. Two independent examiners screened titles/abstracts and selected full-text articles. Studies evaluating titanium dental implant osseointegration in native alveolar bone were included. A quality assessment of reporting was performed. Random-effects meta-analyses and meta-regressions were produced for bone-implant contact (BIC), first BIC, and crestal bone level.Results125 out of 249 full-text articles were reviewed, 55 original studies were included. Quality of reporting was generally low, omissions included animal characteristics, examiner masking/calibration, and sample size calculation. The typical minipig model protocol included surgical extraction of the mandibular premolars and first molar, 12±4 wks post-extraction healing, placement of three narrow regular length dental implants per jaw quadrant, submerged implant healing and 8 wks of osseointegration. Approximately 90% of studies reported undecalcified incandescent light microscopy histometrics. Overall, mean BIC was 59.88% (95%CI: 57.43–62.33). BIC increased significantly over time (p<0.001): 40.93 (95%CI: 34.95–46.90) at 2 wks, 58.37% (95%CI: 54.38–62.36) at 4 wks, and 66.33% (95%CI: 63.45–69.21) beyond 4 wks. Variability among studies was mainly explained by differences in observation interval post-extraction and post-implant placement, and implant surface. Heterogeneity was high for all studies (I2 > 90%, p<0.001).ConclusionsThe minipig intraoral dental implant model appears to effectively demonstrate osseointegration and alveolar bone remodeling similar to that observed in humans and canine models.

Dimensional Changes in the Alveolus after a Combination of Immediate Postextraction Implant and Connective Grafting and/or Socket Shield Technique.

Immediate implant placement protocols after dental extraction have enabled a reduction in surgical phases. This procedure has increased patient satisfaction and similar survival rates to late implant placement procedures. However, placing an implant immediately after dental extraction does not counteract the physiological remodeling of alveolar bone. For this reason, additional surgical techniques have been developed, such as the placement of a connective tissue graft (CTG) or the socket shield technique (SST). Dimensional changes in the peri-implant tissues were observed after placement of immediate implants following the extraction and CTG and/or SST. A total of 26 surgical interventions were carried out in which dimensional change variables of peri-implant tissues were analyzed. The preoperative state and immediate postoperative situation were compared with the situation after one year. Measurements were taken at 3, 5, and 7 mm from the gingival margin and analyzed in this CBCT radiological study (Planmeca Promax 3D). The implant platform was used as a reference point for the measurement of changes in alveolar crest height. One year after performing either of the two techniques (CTG and/or SST), a significant increase in the gingiva thickness and vestibular cortex occurred at 5 mm (0.65 ± 1.16 mm) and 7 mm (0.95 ± 1.45 mm) from the gingival margin. Additionally, an increase in thickness of palatal bone was registered at 3 mm (0.48 ± 0.90 mm). The graft placement group showed an increase in thickness of peri-implant tissue in the vestibular area after one year, although CTG and SST groups were clinically similar. The implementation of SST revealed promising results regarding the buccal thickness of hard and soft tissues after one year. A significant increase in vestibular cortical bone thickness, as well as the overall mucosa thickness and buccal bone at 3 mm from the gingival margin, was observed. A significant reduction in the distance from the bone crest to the platform was detected in both techniques. Both techniques (CTG and SST) are appropriate to provide sufficient volume to peri-implant tissues in the vestibular area of anterior maxillary implants. Some limitations were detected, such as the lack of an aesthetic analysis or small sample size, so results should be interpreted with caution. Future studies are necessary to further evaluate the long-term predictability of these techniques.

Alveolar bone remodeling in virtually planned, bone-grafted vs non-grafted guided flapless implant surgery in the anterior maxilla: a cross-sectional retrospective follow-up study

PurposeIn patients who underwent virtual planning and guided flapless implant surgery for teeth missing in the anterior maxilla, we compared buccal bone loss between those treated with and without autogenous bone augmentation.MethodsOf 22 patients with teeth missing because of trauma or aplasia, 10 (18 implant sites) were reconstructed with buccally placed bone graft harvested from the mandibular ramus, and 12 were non-reconstructed (16 sites). Baseline cone-beam computed tomography allowed for implant planning using the NobelClinician® software and was performed again at 1 year after functional loading. The marginal bone level was assessed radiographically at post-implant baseline and at follow-up.ResultsAt follow-up, buccal bone loss differed significantly between groups at the central level of the implant (p = 0.0005) but not at the coronal level (p = 0.329). The mean marginal bone level change was 0.6 mm, with no significant between-group difference (p = 0.876). The actual implant position often deviated in the vertical or sagittal plane by an average of 0.3–0.6 mm from the planned position.ConclusionCompared with non-reconstructed patients, reconstructed patients experienced significantly more buccal bone loss at the central level of implants. The groups did not differ at the coronal level or in marginal bone loss, possibly because of the more augmented bone at the central level among reconstructed patients. Differences between planned versus actual implant positions should be considered in situations of limited bone volume at the planned implant site.

CCR2+ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling.

During mechanical force-induced alveolar bone remodeling, macrophage-mediated local inflammation plays a critical role. Yet, the detailed heterogeneity of macrophages is still unknown. Single-cell RNA sequencing was used to study the transcriptome heterogeneity of macrophages during alveolar bone remodeling. We identified macrophage subclusters with specific gene expression profiles and functions. CellChat and trajectory analysis revealed a central role of the Ccr2 cluster during development, with the CCL signaling pathway playing a crucial role. We further demonstrated that the Ccr2 cluster modulated bone remodeling associated inflammation through an NF-κB dependent pathway. Blocking CCR2 could significantly reduce the Orthodontic tooth movement (OTM) progression. In addition, we confirmed the variation of CCR2+ macrophages in human periodontal tissues. Our findings reveal that mechanical force-induced functional shift of the Ccr2 macrophages cluster mediated by NF-κB pathway, leading to a pro-inflammatory response and bone remodeling. This macrophage cluster may represent a potential target for the manipulation of OTM.

Effect of Omega-3 On Orthodontic Tooth Movement: A Systematic Review

Orthodontic movement is a continuous and balanced process characterized by resorption and apposition of bone in areas of pressure and tension after mechanical strength forces are applied. The purpose of this systematic review was to determine the effect of omega-3 administration on orthodontic tooth movement from various studies that have been carried out previously. Search articles online using PubMed, ProQuest, Scopus, Ebscohost, and Google Scholar between 1995-2021. The keywords used were (Orthodontic tooth movement OR Orthodontic movement AND bone remodelling OR Alveolar bone remodelling OR Alveolar remodelling AND Omega 3 OR Fatty acids OR EPA DHA). A total of 530 articles were obtained and then screened using titles, abstracts, and can access full text there are 44 articles. Then by using inclusion and exclusion criteria, three full-text journals were obtained and compiled using PRISMA. These studies show that omega-3 administration affects orthodontic tooth movement. Omega 3 can slow down the movement of orthodontic teeth so that it can consider as a method of preventing relapse by giving omega-3 at the end of orthodontic treatment.

GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by P. gingivalis LPS and Concurrent Compression.

Periodontitis is characterized by bacterially induced inflammatory destruction of periodontal tissue. This also affects fibroblasts of the human periodontal ligaments (HPdLF), which play a coordinating role in force-induced tissue and alveolar bone remodeling. Excessive inflammation in the oral tissues has been observed with simultaneous stimulation by pathogens and mechanical forces. Recently, elevated levels of growth differentiation factor 15 (GDF15), an immuno-modulatory member of the transforming growth factor (TGFB) superfamily, were detected under periodontitis-like conditions and in force-stressed PdL cells. In view of the pleiotropic effects of GDF15 in various tissues, this study aims to investigate the role of GDF15 in P. gingivalis-related inflammation of HPdLF and its effect on the excessive inflammatory response to concurrent compressive stress. To this end, the expression and secretion of cytokines (IL6, IL8, COX2/PGE2, TNFα) and the activation of THP1 monocytic cells were analyzed in GDF15 siRNA-treated HPdLF stimulated with P. gingivalis lipopolysaccharides alone and in combination with compressive force. GDF15 knockdown significantly reduced cytokine levels and THP1 activation in LPS-stimulated HPdLF, which was less pronounced with additional compressive stress. Overall, our data suggest a pro-inflammatory role for GDF15 in periodontal disease and demonstrate that GDF15 partially modulates the force-induced excessive inflammatory response of PdLF under these conditions.

Retracted: Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Jianping Zhou, Fengxue Yang, Xiaolin Xu, Gang Feng, Jun Chen, Jinglin Song, Hongwei Dai. Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography. Med Sci Monit, 2018; 24: 8306-8314. DOI: 10.12659/MSM.912470.

Dronabinol inhibits alveolar bone remodeling in tooth movement of rats

Orthodontic tooth movement is reliant on the process of bone remodeling, and a variety of medications impact the ability of teeth to move through bone. Marijuana is the most widely used recreational drug in the world, and early studies suggest the drug impacts bone remodeling as tetrahydrocannabinol binds to cannabinoid receptors which play a role in bone homeostasis. This study aimed to assess the impact of dronabinol on alveolar bone remodeling in rats with otherwise healthy tissue when subjected to orthodontic forces.Thirty male Sprague Dawley rats were equally allocated into 2 groups. Orthodontic appliances were placed in all animals, which consisted of a nickel-titanium coil ligated from the maxillary first molar to the central incisor. The appliance was activated to deliver a force to move teeth together. Over 21 days, daily injections of either dronabinol or the control (solvent) were given to the rats. Cephalometric analysis, histology, and bone remodeling profiles of both groups were analyzed and compared.Teeth moved in both the dronabinol and control groups (P <0.05). Tooth movement in the control group followed the typical process of orthodontic tooth movement: periodontal width narrowing and bone resorption on the compression side of the tooth, with an overall decrease in the height of the alveolar bone. In contrast, the dronabinol group showed an abnormal response to tooth movement: no bone resorption on the compression side of the tooth, increased bone formation on the tension side, and the maintenance of the height of the alveolar crest. In the dronabinol group, there were also significantly more osteoclasts and osteoblasts in the alveolar bone than in the control group.These results demonstrate that dronabinol attenuates orthodontic tooth movement by decreasing bone resorption, which could have implications for other bone-related recovery processes.

MicroRNA-34a and microRNA-146a target CELF3 and suppress the osteogenic differentiation of periodontal ligament stem cells under cyclic mechanical stretch

Background/purposeDuring orthodontic tooth movement, mechanical forces induce the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), which contributes to alveolar bone remodeling. MicroRNAs (miRNAs) are involved in regulating PDLSC osteogenic differentiation. Therefore, we intended to explore the role of miR-34a and miR-146a in osteogenic differentiation of PDLSCs under cyclic stretch. Materials and methodsPhenotypic identification of PDLSCs was determined by flow cytometry analysis. PDLSCs were incubated with osteogenic differentiation medium for 3 weeks and the osteogenic differentiation capability was detected by Alizarin Red staining. To mimic the orthodontic forces, cyclic mechanical stretch was applied to PDLSCs. Alkaline phosphatase (ALP) activity assay and ALP staining were used for evaluating the ALP activity. The expression of osteogenesis markers in PDLSCs was assessed by western blotting and qRT-PCR. The binding between miR-34a (or miR-146a) and CUGBP Elav-like family member 3 (CELF3) was validated by luciferase reporter assay. ResultsCyclic stretch elevated ALP activity and the expression of osteogenesis markers, osteopontin (OPN), runt-related transcription factor 2 (RUNX2), type I collagen (COL1), ALP, osteocalcin (OCN) and osterix (OSX), in PDLSCs. MiR-146a and miR-34a were downregulated in PDLSCs under cyclic stretch. Either overexpressing miR-146a and miR-34a reduced ALP activity and the expression of osteogenesis markers. CELF3 was a target of both miR-146a and miR-34a. CELF3 silencing attenuated while CELF3 overexpression enhanced ALP activity and the expression of osteogenesis markers. ConclusionMiR-34a and miR-146a repress cyclic stretch-induced osteogenic differentiation of PDLSCs via regulating the expression of CELF3.

Mechanosensitive Piezo1 in Periodontal Ligament Cells Promotes Alveolar Bone Remodeling During Orthodontic Tooth Movement.

Orthodontic tooth movement (OTM) is a process depending on the remodeling of periodontal tissues surrounding the roots. Orthodontic forces trigger the conversion of mechanical stimuli into intercellular chemical signals within periodontal ligament (PDL) cells, activating alveolar bone remodeling, and thereby, initiating OTM. Recently, the mechanosensitive ion channel Piezo1 has been found to play pivotal roles in the different types of human cells by transforming external physical stimuli into intercellular chemical signals. However, the function of Piezo1 during the mechanotransduction process of PDL cells has rarely been reported. Herein, we established a rat OTM model to study the potential role of Piezo1 during the mechanotransduction process of PDL cells and investigate its effects on the tension side of alveolar bone remodeling. A total of 60 male Sprague-Dawley rats were randomly assigned into three groups: the OTM + inhibitor (INH) group, the OTM group, and the control (CON) group. Nickel-titanium orthodontic springs were applied to trigger tooth movement. Mice were sacrificed on days 0, 3, 7, and 14 after orthodontic movement for the radiographic, histological, immunohistochemical, and molecular biological analyses. Our results revealed that the Piezo1 channel was activated by orthodontic force and mainly expressed in the PDL cells during the whole tooth movement period. The activation of the Piezo1 channel was essential for maintaining the rate of orthodontic tooth movement and facilitation of new alveolar bone formation on the tension side. Reduced osteogenesis-associated transcription factors such as Runt-related transcription factor 2 (RUNX2), Osterix (OSX), and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio were examined when the function of Piezo1 was inhibited. In summary, Piezo1 plays a critical role in mediating both the osteogenesis and osteoclastic activities on the tension side during OTM.

Oral Osteomicrobiology: The Role of Oral Microbiota in Alveolar Bone Homeostasis.

Osteomicrobiology is a new research field in which the aim is to explore the role of microbiota in bone homeostasis. The alveolar bone is that part of the maxilla and mandible that supports the teeth. It is now evident that naturally occurring alveolar bone loss is considerably stunted in germ-free mice compared with specific-pathogen-free mice. Recently, the roles of oral microbiota in modulating host defense systems and alveolar bone homeostasis have attracted increasing attention. Moreover, the mechanistic understanding of oral microbiota in mediating alveolar bone remodeling processes is undergoing rapid progress due to the advancement in technology. In this review, to provide insight into the role of oral microbiota in alveolar bone homeostasis, we introduced the term “oral osteomicrobiology.” We discussed regulation of alveolar bone development and bone loss by oral microbiota under physiological and pathological conditions. We also focused on the signaling pathways involved in oral osteomicrobiology and discussed the bridging role of osteoimmunity and influencing factors in this process. Finally, the critical techniques for osteomicrobiological investigations were introduced.

N-acetylcysteine promotes cyclic mechanical stress-induced osteogenic differentiation of periodontal ligament stem cells by down-regulating Nrf2 expression

Background/purposeMechanical stress plays a vital role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Cyclic mechanical stress may up-regulate reactive oxygen species (ROS) level. N-acetylcysteine (NAC) possesses powerful antioxidant capacity. However, it is undefined the impact of NAC on osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs. The aim of our research was to study the effect of NAC on PDLSCs during osteogenic differentiation under cyclic mechanical stress. Materials and methodsThe expression levels of osteogenesis markers were used to examine the osteogenic differentiation of PDLSCs. ROS production were measured by flow cytometry. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were analyzed. We also examined the changes of alveolar bone and periodontal ligament (PDL) tissues in orthodontic rats by micro-computed tomography (micro-CT) system and immunohistochemistry (IHC) staining. The nuclear factor erythroid-2-related factor-2 (Nrf2) expression was examined. ResultsNAC could enhance the osteogenic differentiation and up-regulate the GSH level as well as the ratio of GSH/GSSG, while down-regulate ROS generation and Nrf2 expression induced by cyclic mechanical stress in PDLSCs. NAC had beneficial effects on the microstructure of alveolar bone and enhanced the expression levels of osteogenesis markers, such as alkaline phosphatase (ALP) and collagen type 1 (COL1) in PDL in orthodontic rats at the tension side. ConclusionNAC could improve the osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs and in orthodontic rats, suggesting a potential therapeutic approach for alveolar bone remodeling in orthodontics.

Effect of Curcumin on Alterations of Alveolar Bone Remodeling and Expression of Receptor Activator of Nuclear Factor-κ B Ligand in Rat Tooth During Tooth Movement

Objective: To evaluate the effect of Curcumin on Alterations of Alveolar Bone Remodeling and Expression of RANKL in Rat Tooth during Tooth Movement. Methods: 64 SD rats were randomly divided into 4 groups, Model, Adrb2, Cur and Cur + Pro groups. The rat orthodontic teeth movement models were established.The rats were injected corresponding reagents according to weight and were sacrificed on day 0, 7, 14 and 21. The movement distance of first molar of rats was measured by Vernier caliper.The numbers of osteoclasts were observed through TRAP staining. The change of micro-structure of alveolar bone was evaluated by Micro-CT. Results: The trends of the distance of teeth movement and numbers of osteoclast were the same: Cur group β Adrb2 group &gt; Model groups Cur+Pro group (P &lt; 0.05). Micro-CT scan showed that curcumin could reduce the bone volume fraction (BV/TV), bone trabecular density (MTPD), and increase the trabecular resolution (TB. SP). When propranolol was given at the same time, the effect of curcumin disappeared. Conclusion: Curcumin could promote the resorption of alveolar bone at the pressure side and increase the osteoclast numbers so that the alveolar bone became looser which was beneficial to the movement of orthodontic tooth.

Effects of idiopathic hypoparathyroidism on tooth eruption of rats

Objective: To explore the effects of reduced parathyroid function in early growth and development on tooth eruption and enamel development by establishing an animal model of idiopathic hypoparathyroidism (IHP) and to explore the mechanism of IHP affecting tooth eruption with a view to provide experimental basis for early diagnosis and clinical treatment of IHP. Methods: Forty-eight SD rats at postnatal day 7 were randomly and equally divided into sham operation group and IHP group. The bilateral parathyroidectomy (PTX) was performed by using carbon nanoparticles technique to establish an IHP rat model, while no parathyroids were removed in the sham operation group using the same technique. Serum was extracted after surgery, serum calcium, serum phosphorus, and serum parathyroid hormone (PTH) concentrations were detected in order to verify the success of the modeling. At postnatal day 14, day 25 and day 38 (P14, P25 and P38) the rats were sacrificed to collect the mandible samples (six from each group) and to analyze the volume of enamel, the height of the tooth eruption and the bone microarchitecture parameters of the root-oriented alveolar bone of mandibular third molar quantitatively by micro-CT scanning. Histological sections were prepared. The distribution and expression levels of osteoblast differentiation markers runt-related transcription factor 2 (RUNX2) and osterix (OSX) in the alveolar bone around the third molar were detected by immunohistochemical staining and the osteoclast activity was detected by tartrate-resistant acid phosphatase (TRAP) staining. After each of the third molars was isolated, the microhardness of the enamel was measure by using a microhardness tester and the enamel microstructure was photographed by using scanning electron microscope. Primary dental follicle stem cells were isolated from other six mandibulars from each group at P14 and cultured in vitro. The cell proliferation activity was tested by cell colony forming units detection. After induction of dental follicle stem cells into osteogenic differentiation, the degree of mineralization was detected by using alkaline phosphatase staining and alizarin red staining. The mRNA of mandibular tissues and dental follicle cells were extracted, the expression of genes related to osteoblasts and osteoclast differentiations and parathyroid hormone receptor 1 (PTH1R) were detected by real-time quantitative PCR. Results: Bilateral parathyroidectomy was successfully performed on rats with the help of carbon nanoparticles under stereomicroscope. After surgery, the serum calcium concentration reduced, the serum phosphorus concentration increased and the serum PTH concentration distinctly reduced (P<0.01). The volume of enamel [(4.58±0.24) mm3] and the microhardness [(167.76±21.86) MPa] in IHP group were significantly lower than that in sham operation group [(5.22±0.46) mm3, P<0.05; (223.92±10.94) MPa, P<0.01, respectively]. The eruption height of the mandibular third molar in the IHP group was respectively lower than that in the sham operation group (P<0.05). The bone volume over total volume and trabecular number of the root-oriented alveolar bone of the mandibular third molars in the IHP group were respectively lower than that in sham operation group (P<0.05). The expression levels of RUNX2 and OSX proteins in the root-oriented alveolar bone of the mandibular third molars in the IHP group respectively reduced, compared to that in sham operation group (P<0.05). Furthermore, the number of osteoclasts (3.86±1.07) in crown-oriented alveolar bone in the IHP group was respectively lower than that in sham operation group (6.43±1.27) (P<0.01). The proliferative activity of dental follicle stem cells in the IHP group respectively decreased (P<0.01). After the induction of osteogenic differentiation, the mineralization ability of dental follicle stem cells in the IHP group was weakened. In the mandibular tissues of IHP group, the expression levels of osteogenesis related genes such as RUNX2 and OSX and the the expression of PTH1R significantly reduced (P<0.05). The receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio reduced significantly (P<0.01) compared to those of sham operation group. Also in the dental follicle cells of IHP group, the expression levels of osteogenesis related genes such as RUNX2 and OSX, the RANKL/OPG ratio and the expression of PTH1R significantly decreased simultaneously compared to that in sham operation group (P<0.01). Conclusions: Under the condition of idiopathic hypoparathyroidism, the weakening of PTH/PTH1R signaling may reduce the proliferative activity of dental follicle stem cells, inhibit their regulation for osteoblast and osteoclast differentiations and functions, thereby interfere the bone remodeling of alveolar bone around the tooth germ during tooth eruption, which eventually leads to delayed tooth eruption.

Function of Orofacial Stem Cells in Tooth Eruption: An Evolving Perspective.

Tooth eruption is closely linked to the normal development of dentition and proper establishment of occlusion. Disturbances in tooth eruption may affect oral physiological functions, facial contour and aesthetics; it is therefore important to understand the eruption process. This process is a complex biological event involving dynamic changes at the tissue and cellular levels. It is guided by anatomical structures as well as biological and molecular factors that result in the movement of the tooth to its final functional position in the oral cavity. Evidence increasingly suggests that stem cells contribute to tooth development and eruption. Multiple stem cell populations have been discovered in teeth and in their supporting tissues, such as dental follicle precursor cells, orofacial bone-/bone marrow-derived mesenchymal stem cells, periodontal ligament stem cells, stem cells from the apical papilla and dental pulp stem cells. These stem cells exhibit distinct differentiation capacities and are closely linked to alveolar bone remodelling, periodontium development and root formation during the eruption process. The present review summarises the current knowledge of the characteristics and functions of orofacial stem cells in tooth eruption, with a particular focus on recent discoveries concerning their lineage allocation and regulatory mechanisms.

The α-mangostin effect on the quantity of TGF-β1 titer relate to the mandibular bone volume of Rattus novergicus in the periodontitis model

Context: Periodontitis causes pocket formation, gingival recession, and destruction of periodontal ligaments and alveolar bone. Periodontitis disturbs the attachment of periodontal ligaments to the maxillary and mandibular bones. The α-mangostin has shown role-playing in the bone remodeling process. Aims: To evaluate the potential of α-mangostin induce the TGFβ1 titer associated with the increased mandibular bone volume on the alveolar bone remodeling of periodontitis of Rattus novergicus. Methods: The α-mangostin used to the single administration dosage on the rat periodontitis model on the 7 and 14 days. TGF-β1 titer tested by enzyme-linked immunosorbent assay, while the X-Ray Micro-CT/Micro Computed Tomography examined the volume’s development of the mandibular bone. Results: At the 7 days, 0.5 and 1% of α-mangostin had a better effect to increase the bone volume, and TGF-β1 titer has linearity of bone development at concentrations of 0.5 to 2%. At 14 days, 1 and 2% of α-mangostin exhibited a better effect on inducing an increase in mandibular bone volume and TGF-β1 titer. The linearity of both occurs at concentrations of 0.5 to 1%. The Micro-CT of the mandibular bone showed callus or new bone formation at the edge of each treatment group’s lesion as an indicator of bone remodeling. Conclusions: α-Mangostin induced an increase in the TGF-β1 titer, which was in line with the rise in the volume of the mandibular bone of Rattus novergicus.