Cellular and molecular changes in orthodontic tooth movement.
Ontology highlight
ABSTRACT:
SUBMITTER: Zainal Ariffin SH
PROVIDER: S-EPMC3201678 | biostudies-other | 2011
REPOSITORIES: biostudies-other
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Project description:Cementum is a mineralized tissue that covers tooth roots and functions in the periodontal attachment complex. Cementocytes, resident cells of cellular cementum, share many characteristics with osteocytes, are mechanoresponsive cells that direct bone remodeling based on changes in loading. We hypothesized that cementocytes play a key role during orthodontic tooth movement (OTM). To test this hypothesis, we used 8-week-old male Wistar rats in a model of OTM for 2, 7, or 14 days (0.5 N), whereas unloaded contralateral teeth served as controls. Tissue and cell responses were analyzed by high-resolution micro-computed tomography, histology, tartrate-resistant acid phosphatase staining for odontoclasts/osteoclasts, and transmission electron microscopy. In addition, laser capture microdissection was used to collect cellular cementum, and extracted proteins were identified by liquid chromatography coupled to tandem mass spectrometry. The OTM model successfully moved first molars mesially more than 250 μm by 14 days introducing apoptosis in a small number of cementocytes and areas of root resorption on mesial and distal aspects. Cementocytes showed increased nuclear size and proportion of euchromatin suggesting cellular activity. Proteomic analysis identified 168 proteins in cellular cementum with 21 proteins found only in OTM sites and 54 proteins only present in control samples. OTM-down-regulated several extracellular matrix proteins, including decorin, biglycan, asporin, and periostin, localized to cementum and PDL by immunostaining. Furthermore, type IV collagen (COL14A1) was the protein most down-regulated (-45-fold) by OTM and immunolocalized to cells at the cementum-dentin junction. Eleven keratins were significantly increased by OTM, and a pan-keratin antibody indicated keratin localization primarily in epithelial remnants of Hertwig's epithelial root sheath. These experiments provide new insights into biological responses of cementocytes and cellular cementum to OTM.
| S-EPMC8478897 | biostudies-literature
Project description:Clinical evidence has suggested that surgical corticotomy of the alveolar bone can accelerate local orthodontic tooth movement (OTM), but the underlying cell and molecular mechanisms remain largely unclear. The present study examined the role of macrophages played in corticotomy-assisted OTM. Orthodontic nickel-titanium springs were applied to the left maxillary first molars of rats or mice to induce OTM with or without corticotomy. Corticotomy enhanced OTM distance by accelerating movement through induction of local osteoclastogenesis and macrophage infiltration during OTM. Further analysis showed that macrophages were polarized toward an M1-like phenotype immediately after corticotomy and then switched to an M2-like phenotype during OTM. The microenvironment of corticotomy induced macrophage infiltration and polarization through the production of TNF-α. More importantly, the amount of OTM induced by corticotomy was significantly decreased after mice were depleted of monocyte/macrophages by injection of liposome-encapsulated clodronate. Further experiments by incubating cultured macrophages with fresh tissue suspension obtained from post-corticotomy gingiva switched the cells to an M1 phenotype through activation of the nuclear factor-κB (NF-κB) signaling pathway, and to an M2 phenotype through activation of the JAK/STAT3 signaling pathway. Our results suggest that corticotomy induces macrophage polarization first by activating the NF-κB signaling pathway and later by activating the JAK/STAT3 signaling pathway, and that these processes contribute to OTM by triggering production of inflammatory cytokines and osteoclastogenesis.
| S-EPMC6235963 | biostudies-literature
Project description:The stromal cell-derived factor 1 (SDF-1)/chemokine receptor type 4 (CXCR4) axis plays a key role in alveolar bone metabolism during orthodontic tooth movement (OTM). Herein, the effects of the SDF-1/CXCR4 axis on the regional acceleratory phenomenon (RAP) in OTM velocity and on changes in the surrounding periodontium after adjacent tooth extraction in rats were investigated. Six-week-old male Wistar/ST rats underwent left maxillary first molar (M1) extraction and mesial OTM of the left maxillary second molar (M2) with a 10-g force closed-coil spring. Phosphate-buffered saline, immunoglobulin G (IgG) isotype control antibody, or anti-SDF-1 neutralizing monoclonal antibody were injected at the M1 and M2 interproximal areas (10 μg/0.1 mL) for the first three days. Analyses were performed after 1, 3, and 7 days (n = 7). The results demonstrated a significant increase in SDF-1 expression from day 1, which was effectively blocked via anti-SDF-1 neutralizing monoclonal antibody injection. On day 3, the M2 OTM distance and the number of positively stained osteoclasts significantly reduced alongside a reduction in inflammatory markers in the experimental group. Our results demonstrated that serial local injection of the anti-SDF-1 neutralizing monoclonal antibody reduces M2 OTM, osteoclast accumulation, and localized inflammatory responses in an OTM model with tooth extraction-induced RAP.
| S-EPMC10904391 | biostudies-literature
Project description:Orthodontic tooth movement (OTM) is a "sterile" inflammatory process. The present study aimed to reveal the underlying biological mechanisms, by studying the force associated-gene expression changes, in a time-dependent manner. Ni-Ti springs were set to move the upper 1st-molar in C57BL/6 mice. OTM was measured by ?CT. Total-RNA was extracted from tissue blocks at 1,3,7 and 14-days post force application, and from two control groups: naïve and inactivated spring. Gene-expression profiles were generated by next-generation-RNA-sequencing. Gene Set Enrichment Analysis, K-means algorithm and Ingenuity pathway analysis were used for data interpretation. Genes of interest were validated with qRT-PCR. A total of 3075 differentially expressed genes (DEGs) were identified, with the greatest number at day 3. Two distinct clusters patterns were recognized: those in which DEGs peaked in the first days and declined thereafter (tissue degradation, phagocytosis, leukocyte extravasation, innate and adaptive immune system responses), and those in which DEGs were initially down-regulated and increased at day 14 (cell proliferation and migration, cytoskeletal rearrangement, tissue homeostasis, angiogenesis). The uncovering of novel innate and adaptive immune processes in OTM led us to propose a new term "Immunorthodontics". This genomic data can serve as a platform for OTM modulation future approaches.
| S-EPMC7235241 | biostudies-literature
Project description:UnlabelledEnoxacin inhibits binding between the B-subunit of vacuolar H(+)-ATPase (V-ATPase) and microfilaments, and also between osteoclast formation and bone resorption in vitro. We hypothesized that a bisphosphonate derivative of enoxacin, bis-enoxacin (BE), which was previously studied as a bone-directed antibiotic, might have similar activities. BE shared a number of characteristics with enoxacin: It blocked binding between the recombinant B-subunit and microfilaments and inhibited osteoclastogenesis in cell culture with IC50s of about 10 µM in each case. BE did not alter the relative expression levels of various osteoclast-specific proteins. Even though tartrate-resistant acid phosphatase 5b was expressed, proteolytic activation of the latent pro-enzyme was inhibited. However, unlike enoxacin, BE stimulated caspase-3 activity. BE bound to bone slices and inhibited bone resorption by osteoclasts on BE-coated bone slices in cell culture. BE reduced the amount of orthodontic tooth movement achieved in rats after 28 days. Analysis of these data suggests that BE is a novel anti-resorptive molecule that is active both in vitro and in vivo and may have clinical uses.AbbreviationsBE, bis-enoxacin; V-ATPase, vacuolar H(+)-ATPase; TRAP, tartrate-resistant acid phosphatase; ?MEM D10, minimal essential media, alpha modification with 10% fetal bovine serum; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; RANKL, receptor activator of nuclear factor kappa B-ligand; NFATc1, nuclear factor of activated T-cells; ADAM, a disintegrin and metalloprotease domain; OTM, orthodontic tooth movement.
| S-EPMC3775373 | biostudies-literature
Project description:Recently, involvement of the sympathetic nervous system in bone metabolism has attracted attention. β2-Adrenergic receptor (β2-AR) is presented on osteoblastic and osteoclastic cells. We previously demonstrated that β-AR blockers at low dose improve osteoporosis with hyperactivity of the sympathetic nervous system via β2-AR blocking, while they may have a somewhat inhibitory effect on osteoblastic activity at high doses. In this study, the effects of butoxamine (BUT), a specific β2-AR antagonist, on tooth movement were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and closed-coil springs were inserted into the upper-left first molar. After sacrifice, we calculated the amount of tooth movement and analyzed the trabecular microarchitecture and histomorphometry. The distance in the SHR control was greater than that in the Wistar-Kyoto rat group, but no significant difference was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control. Analysis of bone volume per tissue volume, trabecular number, and osteoclast surface per bone surface in the alveolar bone showed clear bone loss by an increase of bone resorption in SHR. In addition, BUT treatment resulted in a recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the periodontal ligament were increased by tooth movement, and BUT administration decreased TH-immunoreactive nerves. These results suggest that BUT prevents alveolar bone loss and orthodontic tooth movement via β2-AR blocking.
| S-EPMC4293756 | biostudies-literature
Project description:Objectives: Myeloid p38α/MAPK regulate and coordinate osteoclastogenesis. The present study was conducted to investigate the role of myeloid p38α/MAPK during orthodontic tooth movement. Methods: Orthodontic tooth movement was performed in wildtype and p38αΔmyel mice lacking p38α/MAPK expression in myeloid cells. First, bone parameter as well as osteoblast and osteoclast number were determined in tibiae. RNA was isolated from the untreated and orthodontically treated maxillary jaw side and expression of genes involved in inflammation and bone remodelling were analysed. Finally, periodontal bone loss, alveolar bone density and extent of orthodontic tooth movement were assessed. Results: Bone density was increased in p38αΔmyel mice compared to wildtype mice in tibiae (p = 0.043) and alveolar bone (p = 0.003). This was accompanied by a reduced osteoclast number in tibiae (p = 0.005) and TRAP5b in serum (p = 0.015). Accordingly, expression of osteoclast-specific genes was reduced in p38αΔmyel mice. Extent of tooth movement was reduced in p38αΔmyel mice (p = 0.024). This may be due to the higher bone density of the p38αΔmyel mice. Conclusions: Myeloid p38α/MAPK thus appears to play a regulatory role during orthodontic tooth movement by regulating osteoclastogenesis.
| S-EPMC9000068 | biostudies-literature
Project description:BACKGROUND This study was performed to investigate the effect of local injection of asperosaponin VI (ASA VI) on the orthodontic tooth movement in rats. MATERIAL AND METHODS A total of 64 healthy female Sprague-Dawley rats were selected and divided into 2 groups randomly: the ASA VI group and the control group. For the ASA VI group, 10 mg/kg ASA VI solution was injected into buccal submucoperiosteal of bilaterally first maxillary molars, and the same volume of normal saline was given to the control group. The orthodontic force was applied to the maxillary first molars. All rats were sacrificed on days 3, 7, or 14. Tooth movement effects on the periodontium were analyzed through hematoxylin and eosin (H&E) staining, tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemistry analysis. Tooth movement measurements and alveolar bone volumetric changes were analyzed using a micro-computed tomography (CT) scan. Molecular changes were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. RESULTS The ASA VI group presented with a significant increase of tooth movement, osteoclast number, and the expression of osteoclast differentiation factor (ODF) compared with the control group. ASA VI also induced a significant decrease in bone volume and density and an increase in trabecular spacing and RANKL (receptor activator of nuclear factor kappa-B ligand) expression at the compression side. Furthermore, ASA VI stimulated bone formation on the tension side by enhancing OCN (osteocalcin) expression and RUNX2 (runt-related transcription factor 2) expression, increasing bone volume and density and decreasing in trabecular spacing. CONCLUSIONS Injection of ASA VI may accelerate tooth movement via increasing the activity of osteoclasts, stimulating bone resorption at the compression side. Furthermore, ASA VI has a positive effect on bone formation at the tension side.
| S-EPMC7193222 | biostudies-literature
Project description:An OTM-related healing model was established where a maxillary second premolar was protracted into the critical-sized defect for 6 weeks (Group DT6). As controls, natural healing models without OTM were set at 2 weeks (Group D2) and at 6 weeks (Group D6) after surgery. Total RNAs were extracted from dissected regenerated tissues and additionally from sound alveolar bone as a baseline (Group C). mRNA profiling was performed using microarray analysis.
2017-08-01 | GSE85459 | GEO
Project description:BackgroundAccelerating orthodontic tooth movement (OTM) through biologically effective methods, such as increasing osteoclast-mediated alveolar resorption, could effectively shorten treatment time.ObjectiveTo evaluate an injectable formulation containing receptor activator of nuclear factor kappa-B ligand (RANKL) on the OTM.Materials and methodsWe fabricated a RANKL formulation from 100 µl of 100 µg/ml RANKL adsorbed on 10 mg of poly(lactic acid-co-glycolic acid) microspheres embedded in a 10 wt% aqueous hydroxyethyl cellulose carrier gel. We characterized these formulations for the rate of RANKL release, and then tested for bioactivity using in vitro cell culture. In vivo OTM studies were conducted using 15 week old male Wistar rats for 14 days. We injected the RANKL formulations palatal to the left maxillary first molar and accomplished OTM with a nickel-titanium (NiTi) coil spring applying 5-8 g force. Control groups involved the application of NiTi coil spring with and without placebo formulation. The outcome measure included the distance of tooth movement, bone volume fraction, tissue density, and root volume determined with micro-computed tomography. We determined the amount of osteoclast activity using tartrate-resistant acid phosphatase (TRAP) staining.ResultsThese formulations were able to sustain the release of RANKL for more than 30 days, and the released RANKL showed a positive effect on mice osteoclast precursor cells (RAW 264.7). Reported injectable RANKL formulations were effective in accelerating OTM compared with other control groups, with 129.2 per cent more tooth movement than no formulation and 71.8 per cent more than placebo formulation, corresponding with a significant increase in the amount of TRAP activity. We did not observe any significant differences in root resorption between the groups.ConclusionOur study shows a significant increase in OTM with injectable formulations containing RANKL.
| S-EPMC7311078 | biostudies-literature