Alveolar Bone Remodeling Research Articles

Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp-/- mice.

Orthodontic Force Induces Systemic Inflammatory Monocyte Responses

Periodontal inflammation and alveolar bone remodeling during orthodontic tooth movement are considered regional reactions. However, how systemic immune responses are involved in this regional reaction remains unclear. In this study, we explored the systemic effects of orthodontic force by focusing on the mononuclear phagocyte system. Flow cytometric analysis showed that the percentage of inflammatory monocytes, in peripheral blood and in the monocyte reservoir spleen, decreased on days 1 and 3 and then recovered on day 7 after force application. Along with the systemic decrease of inflammatory monocyte percentage, the number of tartrate-resistant acid phosphatase–positive osteoclasts increased in the compression side of the periodontal tissue during orthodontic tooth movement. Systemic transfusion of enhanced green fluorescent protein–labeled inflammatory monocytes showed recruitment of these monocytes to the orthodontic force compression side of periodontal tissues. These monocytes were colocalized with tartrate-resistant acid phosphatase–positive osteoclasts. In vivo and in vitro experiments showed that orthodontic force could upregulate the expression of pivotal monocyte chemokine monocyte chemotactic protein 1 in periodontal tissues or cultured periodontal ligament cells, which may contribute to monocyte recruitment to regional sites. These data suggest that orthodontic force induces systemic immune responses related to inflammatory monocytes and that systemic inflammatory monocytes can be recruited to periodontal tissues by orthodontic force stimulus.

Micro-osteoperforations: Minimally invasive accelerated tooth movement

Safe, minimally invasive, and cost-effective treatments are being sought to shortened orthodontic treatment time. Based on the well-known principle that orthodontic force triggers inflammatory pathways and osteoclast activity, we hypothesized that controlled micro-trauma in the form of micro-osteoperforations (MOPs) will amplify the expression of inflammatory markers that are normally expressed during orthodontic treatment and that this amplified response will accelerate both bone resorption and tooth movement. We tested our hypothesis in an animal model and in a human clinical trial. In adult rats, MOPs treatment significantly increased molar protraction with concomitant increase in inflammatory cytokine expression, osteoclastogenesis, and alveolar bone remodeling. Likewise, in human subjects, MOPs increased the rate of canine retraction concomitant with increased TNFα and IL-1β levels in gingival crevicular fluid. Moreover, MOPs treatment did not produce additional pain or discomfort in the patients tested. Our data supports our conclusion that MOPs offers a safe, minimally invasive, and easy mechanism to accelerate orthodontic tooth movement. Safe, minimally invasive, and cost-effective treatments are being sought to shortened orthodontic treatment time. Based on the well-known principle that orthodontic force triggers inflammatory pathways and osteoclast activity, we hypothesized that controlled micro-trauma in the form of micro-osteoperforations (MOPs) will amplify the expression of inflammatory markers that are normally expressed during orthodontic treatment and that this amplified response will accelerate both bone resorption and tooth movement. We tested our hypothesis in an animal model and in a human clinical trial. In adult rats, MOPs treatment significantly increased molar protraction with concomitant increase in inflammatory cytokine expression, osteoclastogenesis, and alveolar bone remodeling. Likewise, in human subjects, MOPs increased the rate of canine retraction concomitant with increased TNFα and IL-1β levels in gingival crevicular fluid. Moreover, MOPs treatment did not produce additional pain or discomfort in the patients tested. Our data supports our conclusion that MOPs offers a safe, minimally invasive, and easy mechanism to accelerate orthodontic tooth movement.

The effects of low-intensity pulsed ultrasound on the rate of orthodontic tooth movement

Accelerating alveolar bone remodeling and thus accelerating the velocity of orthodontic tooth movement is highly desirable by orthodontists and patients. Low-intensity pulsed ultrasound (LIPUS) stimulation has been reported to promote fracture healing to treat bone nonunion, and to accelerate bone maturation and remodeling during the consolidation stage of distraction osteogenesis. Low-intensity pulsed ultrasound (LIPUS) is a safe, non-invasive approach, which has demonstrated the potential to increase the rate of tooth movement. The purpose of this review article is to help readers understand the science behind this technology and to discuss the different potential applications of LIPUS in orthodontics.

The level’s changing of transforming growth factor β2 during canine retraction in non-growing age patient

Background: Orthodontic tooth movement occurred as a result of alveolar bone remodeling and collagen due to mechanical load. This mechanical load applied to the tooth will exert a number of cytokine and growth factors. One of the growth factors that are often associated with orthodontic tooth movement is transforming growth factor- β (TGF- β ). It has 3 isoforms, TGF- β 1, TGF- β 2, and TGF- β 3. It has been known that in adult patient, tooth movement rate was slower. Purpose: The aim of this study was to investigate the changing level of TGF- β 2 in non-growing patient due to mechanical load in canine retraction. Method: Gingival crevicular fluid from 6 subjects who undergo canine retraction was taken to investigate changing level of TGF- β 2. Distal site of each upper canine served as an experimental tooth. The gingival crevicular fluid from experimental tooth was taken just prior to mechanical load, at 24h and 72h after mechanical load. Result: ELISA reader showed that level of TGF- β 2 was decreasing during experiment time. Conclusion: It can be concluded that in non-growing patient, TGF- β 2 has less role in alveolar bone resorption in orthodontic tooth movement.

Immunohistochemical localization of tenascin-C in rat periodontal ligament with reference to alveolar bone remodeling.

We investigated the immunohistochemical localization of tenascin-C in 8-week-old rat periodontal ligaments. Tenascin-C immunoreactivity was detected in zones along with cementum and alveolar bone, and more intensely on the resorption surface of alveolar bone than on the formation surface. On the resorbing surface, tenascin-C immunoreactivity was detected in Howship's lacunae without osteoclasts, and in the interfibrous space of the periodontal ligaments, indicating that this molecule works as an adhesion molecule between bone and fibers of periodontal ligaments. Upon experimental tooth movement by inserting elastic bands (Waldo method), the physiological resorption surface of alveolar bone under compressive force showed enhanced bone resorption and enhanced tenascin-C immunoreactivity. However, on the physiological bone formation surface under compressive force, bone resorption was seen only occasionally, and no enhanced tenascin-C immunoreactivity was noted. In an experiment involving excessive occlusal loading to rat molars, transient bone resorption occurred within interradicular septa, but no enhanced tenascin-C immunoreactivity was seen in the periodontal ligaments. These results indicate that tenascin-C works effectively on the bone resorbing surface of physiological alveolar bone remodeling sites, rather than on the non-physiological transient bone resorbing surface. Fibronectin immunoreactivity was distributed evenly in the periodontal ligaments under experimental conditions. Co-localization of tenascin-C and fibronectin immunoreactivity was observed in many regions, but mutually exclusive expression patterns were also seen in some regions, indicating that fibronectin might not be directly involved in alveolar bone remodeling, but may play a role via interaction with tenascin-C.

PROFIL OSTEOBLAS DAN OSTEOKLAS TULANG ALVEOLAR PADA MODEL TIKUS DIABETES TAHAP AWAL DENGAN APLIKASIGAYA ORTODONTI YANG BERBEDA

<p><em>Orthodontic tooth movement is obtained through </em><em>alveolar bone remodeling</em><em>. Alveolar bone remodeling includes reso</em><em>rption</em><em> process </em><em>that </em><em>played by osteoclasts and </em><em>bone formed</em><em> process </em><em>that </em><em>played by osteoblasts. Diabetes affects </em><em>on </em><em>orthodontic tooth movement. </em><em>The magnitude of</em><em> orthodontic force </em><em>that</em><em> applied </em><em>in</em><em> the early stages of diabetic conditions,</em><em> would be</em><em> a consideration of the </em><em>alveolar bone</em><em> remodeling process. The purpose of this study was to determine osteo</em><em>b</em><em>last and osteo</em><em>c</em><em>last</em><em> profile </em><em>in </em><em>early stage of rat diabetic </em><em>models </em><em>with different</em><em> orthodontic force application. 2</em><em>4</em><em> Wistar rats were divided into </em><em>three</em><em> groups of control</em><em>s andthree groups of early stage of</em><em> diabetic treatment with different orthodontic force application (10, 20, and 30 </em><em>gramforce</em><em>/</em><em>g</em><em>r</em><em>f). The results showed an increase</em><em>d </em><em>of osteoclast</em><em> numbers in early stage of</em><em> diabet</em><em>es and will be increased along with the increased of orthodontic force. </em><em>The results </em><em>also </em><em>showed</em><em> a decreased of </em><em>osteoblast</em><em> number in early stage of</em><em> diabet</em><em>es, but it would be increased along with the increased of orthodontic force</em><em>. </em></p>

Antiosteoclastogenesis activity of a CO2 laser antagonizing receptor activator for nuclear factor kappaB ligand-induced osteoclast differentiation of murine macrophages

Macrophage cells are the important effector cells in the immune reaction which are indispensable for osteoclastogenesis; their heterogeneity and plasticity renders macrophages a primer target for immune system modulation. In recent years, there have been very few studies about the effects of macrophage cells on laser treatment-regulated osteoclastogenesis. In this study, RAW 264.7 macrophage cells were treated with RANKL to regulate osteoclastogenesis. We used a CO2 laser as a model biostimulation to investigate the role of osteoclastogenic. We also evaluated cell viability, cell death and cathepsin K expression. The CO2 laser inhibited a receptor activator of the NF-ĸB ligand (RANKL)-induced formation of osteoclasts during the osteoclast differentiation process. It was also found that irradiation for two times reduced RANKL-enhanced TRAP activity in a dose-dependent manner. Furthermore, CO2 laser-treatment diminished the expression and secretion of cathepsin K elevated by RANKL and was concurrent with the inhibition of TRAF6 induction and NF-ĸB activation. The current report demonstrates that CO2 laser abrogated RANKL-induced osteoclastogenesis by retarding osteoclast differentiation. The CO2 laser can modulate every cell through dose-dependent in vitro RANKL-mediated osteoclastogenesis, such as the proliferation and fusion of preosteoclasts and the maturation of osteoclasts. Therefore, the current results serve as an improved explanation of the cellular roles of macrophage cell populations in osteoclastogenesis as well as in alveolar bone remodeling by CO2 laser-treatment.

Difference of natural teeth and implant-supported restoration: A comparison of bone remodeling simulations

Background/purposeAlthough there are existing numerical simulation studies on biomechanical responses induced by dental implants, particular attention has not been paid to the discrepancies of alveolar bone around natural teeth and dental implants. The purpose of this study was to compare and assess the different consequences of alveolar bone remodeling before and after dental implantation. Materials and methodsTwo three-dimensional finite element (FE) models of a maxillary bone segment were developed, comprising either implant-supported dental bridgework or natural teeth. A set of three-dimensional orthotropic bone remodeling algorithms was implemented in the FE models to analyze the stress, strain, and density distribution in the supporting bone. ResultsThere were significant differences in the stress, strain, and density distribution between the intact model and implanted model. The variation of stress value was remarkably different in both models, and evident differences were found in the high stress region. Strain value was elevated in cortical bone around the implant neck, but in the intact bone strain value was distributed more evenly. In addition, bone density distribution around natural teeth was more uniform and homogeneous. ConclusionSimulations of adaptive bone remodeling, validated by clinical data, can be proved as a useful way to bring more insight into the mechanisms behind bone adaptation. In consideration of the crucial role of the periodontal ligament (PDL) in determining the mechanical environment in alveolar bone, it is suggested that the effect of the PDL on the bone remodeling response should be considered in future dental implant design.

Hypotonic Stress Induces RANKL via Transient Receptor Potential Melastatin 3 (TRPM3) and Vaniloid 4 (TRPV4) in Human PDL Cells

Bone remodeling occurs in response to various types of mechanical stress. The periodontal ligament (PDL) plays an important role in mechanical stress–mediated alveolar bone remodeling. However, the underlying mechanism at the cellular level has not been extensively studied. In this study, we investigated the effect of shear stress on the expression of bone remodeling factors, including receptor activator of nuclear factor–kappa B (NF-κB) ligand (RANKL) and osteoprotegerin (OPG), as well as its upstream signaling pathway in primary human PDL cells. We applied hypotonic stress to reproduce shear stress to PDL cells. Hypotonic stress induced the messenger RNA (mRNA) and protein expression of RANKL but not OPG. It also increased intracellular Ca2+ concentration ([Ca2+]i). Extracellular Ca2+ depletion and nonspecific plasma membrane Ca2+ channel blockers completely inhibited the increase in both [Ca2+]i and RANKL mRNA expression. We identified the expression and activation of transient receptor potential melastatin 3 (TRPM3) and vaniloid 4 (TRPV4) channels in PDL cells. Pregnenolone sulfate (PS) and 4α-phorbol 12, 13-didecanoate (4α-PDD), which are agonists of TRPM3 and TRPV4, augmented Ca2+ influx and RANKL mRNA expression. Both pharmacological (2-aminoethoxydiphenyl borate [2-APB], ruthenium red [RR], ononetin [Ono], and HC 067047 [HC]) and genetic (small interfering RNA [siRNA]) inhibitors of TRPM3 and TRPV4 reduced the hypotonic stress–mediated increase in [Ca2+]i and RANKL mRNA expression. Our study shows that hypotonic stress induced RANKL mRNA expression via TRPM3- and TRPV4-mediated extracellular Ca2+ influx and RANKL expression. This signaling pathway in PDL cells may play a critical role in mechanical stress–mediated alveolar bone remodeling.

Systemic effects of fluoxetine on the amount of tooth movement, root resorption, and alveolar bone remodeling during orthodontic force application in rat

Antidepressant drugs such as fluoxetine are of the most commonly used drugs among the public. These drugs may impact the regulation of bone cell functioning, and thus affect orthodontic tooth movement. The aim of this study was to determine the effect of fluoxetine on tooth movements during orthodontic treatment in rats. In this study, 30 male rats were randomly assigned into two groups and injected with fluoxetine 10 mg/kg (experimental group) and normal saline (control group) for a period of 1-month intraperitoneally 5 times/week. Then, the rats were anesthetized and a nickel-titanium closed-coil spring was placed between the left maxillary first molar and left maxillary central incisors of all samples, and then fluoxetine (experimental group) and normal saline (control group) were injected for another 3 weeks by the same method. After measuring tooth movements, rats were sacrificed, and histomorphometric analyses were conducted and the obtained data were statistically analyzed using independent t-test and the significance was set at 0.05. Following the fluoxetine injection, the mean amount of tooth movements in the experimental group was reduced compared to the control group, which was not statistically significant (P = 0.14). There was no significant difference between the two groups regarding bone apposition rate (P = 0.83), external root resorption rate (P = 0.1), and mean number of root resorption lacunae (P = 0.16). Within the limitations of this study, systemic use of fluoxetine may cause insignificant reduction of tooth movement rate in rats; however, this subject needs more evaluations.

Bmp2 and Bmp4 accelerate alveolar bone development

Alveolar bone remodeling is a continuous process that takes place during development and in response to various physiological and pathological stimuli. However, detailed knowledge regarding the underlying mechanisms involved in alveolar bone development is still lacking. This study aims at improving our understanding of alveolar bone formation and the role of bone morphogenetic proteins (Bmps) in this process. Mice at embryonic (E) day 13.5 to postnatal (PN) day 15.5 were selected to observe the process of alveolar bone development. Alveolar bone development was found to be morphologically observable at E14.5. Molar teeth isolated from mice at PN7.5 were pretreated with Bmp2, Bmp4, Noggin, or BSA, and grafted subcutaneously into mice. The subcutaneously implanted tooth germs formed alveolar bone indicating the role of the dental follicle in alveolar bone development. Alveolar bone formation was increased after pretreatment with Bmp2 and Bmp4, but not with Noggin. Gene expression levels in dental follicle cells from murine molars were also determined by real-time RT-PCR. The expression levels of Runx2, Bsp, and Ocn were significantly higher in dental follicle cells cultured with Bmp2 or Bmp4, and significantly lower in those cultured with Noggin when compared with that of the BSA controls. Our results suggest that the dental follicle participates in alveolar bone formation and Bmp2/4 appears to accelerate alveolar bone development.

Multi-level synchrotron radiation-based microtomography of the dental alveolus and its consequences for orthodontics

Multilevel synchrotron radiation-based microtomography has been performed on a human jaw segment obtained at autopsy by cutting increasingly smaller samples from the original segment. The focus of this study lay on the microstructure of the interface between root, periodontal ligament (PDL) and alveolar bone in order to find an answer to the question why alveolar bone remodels during orthodontic loading, when the associated stress and strain levels calculated with finite element analyses are well below the established threshold levels for bone remodeling.While the inner surface of the alveolus appears to be rather smooth on the lower resolution scans, detailed scans of the root–PDL–bone interface reveal that on a microscopical scale it is actually quite rough and uneven with bony spiculae protruding into the PDL space. Any external (orthodontic) loading applied to the root, when transferred through the PDL to the alveolar bone, will cause stress concentrations in these spiculae, rather than be distributed over a “smooth surface”. As osteocyte lacunae are shown to be present in these spiculae, the local amplified stresses and strain can well be registered by the mechano-sensory network of osteocytes. In addition, a second stress amplification mechanism, due to the very presence of the lacunae themselves, is evidence that stresses and strains calculated with FE analyses, based on macroscopical scale models of teeth and their supporting structures, grossly underestimate the actual mechanical loading of alveolar bone at tissue level. It is therefore hypothesized that remodeling of alveolar bone is subject to the same biological regulatory process as remodeling in other bones.

Wnt5a regulates dental follicle stem/progenitor cells of the periodontium.

IntroductionDental follicle gives rise to one or several tissues of the periodontium including the periodontal ligament, cementum and/or alveolar bone. Whether Wnt5a is expressed in the postnatal periodontium or regulates dental follicle stem/progenitor cells is unknown.MethodsDental follicle stem/progenitor cells were isolated from postnatal day 1 (p1) to p11 from rat mandibular first molars. Immunolocalization mapped Wnt5a expression in the alveolar bone, periodontal ligament, and the developing ameloblast and odontoblast layers. Mononucleated and adherent cells were isolated from p7 dental follicle. Wnt5a was overexpressed in dental follicle stem/progenitor cells to study their proliferation, osteogenic differentiation and migration behavior, with subpopulations of native dental follicle stem/progenitor cells as controls, using real-time PCR (Taqman), Lenti-viral transfection, Western blotting and immunofluorescence.ResultsWnt5a was expressed consistently in p1 to p11 rat peridontium. Native, p7 dental follicle stem/progenitor cells had modest ability to mineralize in the tested 14 days. Even in chemically defined osteogenesis medium, dental follicle stem/progenitor cells only showed modest mineralization. Upon addition of 300 ng/mL Wnt5a protein in osteogenesis medium, dental follicle stem/progenitor cells displayed mineralization that was still unremarkable. Chemically induced or Wnt5a-induced mineralization of dental follicle cells only occurred sparsely. Combination of Wnt5a with 100 ng/mL BMP2 finally prompted dental follicle stem/progenitor cells to produce robust mineralization with elevated expression of Runx2, alkaline phosphatase, collagen 1α1 and osteocalcin. Thus, native dental follicle stem/progenitor cells or some of their fractions may be somewhat modest in mineralization. Strikingly, Wnt5a protein significantly augmented RANKL ligand, suggesting putative regulatory roles of dental follicle stem/progenitor cells for the monocyte/osteoclast lineage and potential involvement in alveolar bone remodeling and/or resorption. P-Jnk1/2 was activated in Wnt5a overexpressed dental follicle cells; conversely, exposure to SP600125, a c-Jun N-terminal kinase (JNK) inhibitor attenuated Runx2, collagen 1α1 and osteocalcin expression either in the presence or absence of Wnt5a. Wnt5a overexpression in dental follicle stem/progenitor cells significantly reduced their proliferation rates, but robustly augmented their migration capacity.ConclusionsThese findings provide a glimpse of Wnt5a’s putative roles in dental follicle stem/progenitor cells and the periodontium with implications in periodontal disease, tooth eruption, dental implant bone healing and orthodontic tooth movement.

Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement

The sympathetic nervous system (SNS) regulates bone resorption through β-2 adrenergic receptor (Adrb2). In orthodontic tooth movement (OTM), mechanical force induces and regulates alveolar bone remodeling. Compressive force-associated osteoclast differentiation and alveolar bone resorption are the rate-limiting steps of tooth movement. However, whether mechanical force can activate Adrb2 and thus contribute to OTM remains unknown. In this study, orthodontic nickel-titanium springs were applied to the upper first molars of rats and Adrb1/2-/- mice to confirm the role of SNS and Adrb2 in OTM. The results showed that blockage of SNS activity in the jawbones of rats by means of superior cervical ganglion ectomy reduced OTM distance from 860 to 540 μm after 14 d of force application. In addition, the injection of nonselective Adrb2 agonist isoproterenol activated the downstream signaling of SNS to accelerate OTM from 300 to 540 μm after 7 d of force application. Adrb1/2-/- mice showed significantly reduced OTM distance (19.5 μm) compared with the wild-type mice (107.6 μm) after 7 d of force application. Histopathologic analysis showed that the number of Adrb2-positive cells increased in the compressive region of periodontal ligament after orthodontic force was applied on rats. Mechanistically, mechanical compressive force upregulated Adrb2 expression in primary-cultured human periodontal ligament cells (PDLCs) through the elevation of intracellular Ca2+ concentration. Activation of Adrb2 in PDLCs increased the RANKL/OPG ratio and promoted the peripheral blood mononuclear cell differentiation to osteoclasts in the cocultured system. Upregulation of Adrb2 in PDLCs promoted osteoclastogenesis, which accelerated OTM through Adrb2-enhanced bone resorption. In summary, this study suggests that mechanical force-induced Adrb2 activation in PDLCs contributes to SNS-regulated OTM.

Changes in the spatial distribution of sclerostin in the osteocytic lacuno-canalicular system in alveolar bone due to orthodontic forces, as detected on multimodal confocal fluorescence imaging analyses

ObjectiveMechanical loading on the bone is sensed by osteocytes. Sclerostin is a molecule secreted by osteocytes that is downregulated by mechanical loading; therefore, its expression level is a potent sensor that indicates the spatial transduction of biomechanical properties in bone. This study applied macroconfocal microscopy to observe the spatial response of alveolar bone to orthodontic forces after immunofluorescence using anti-sclerostin antibodies. DesignOrthodontic tooth movement with the Ni–Ti closed-coil spring was applied between the upper bilateral incisors and the left first molar of mice. Four days after this application, the animals were subjected to multimodal confocal fluorescence imaging analyses. ResultsObvious downregulation of sclerotin in the osteocytic lacuna-canalicular system (LCS) was observed specifically in tensile sites of alveolar bone. Confocal-based three-dimensional fluorescence morphometry further quantitatively demonstrated that the distribution and expression of sclerostin in the tensile sites was significantly reduced compared to that observed in the corresponding control sites. Interestingly, the levels of sclerotin signals in the compression sites were significantly higher than those observed in the control sites, although the distribution of sclerotin was not significantly different. ConclusionsOur observations suggest that spatial changes in the level and distribution of sclerostin in the alveolar LCS trigger successive bone remodelling due to orthodontic tooth movement. The multimodal confocal imaging analyses applied in this work will enhance comprehensive understanding regarding the spatial regulation of molecules of interest from the tissue to the cellular level.

Effects of occlusal hypofunction and its recovery on PDL structure and expression of VEGF and bFGF in rats.

The purpose of this study was to clarify whether occlusal hypofunction and its recovery affect the structure of the periodontal ligament (PDL) and expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in rats. Forty-eight Wistar rats aged 5weeks were used and randomly divided into three groups: the hypofunctional group (HG), recovery group (RG), and control group (CG). In HG and RG, appliances were attached to the maxillary and mandibular incisors. In HG, appliances were set for 11weeks. In RG, appliances were set for 7weeks. Appliances were then removed at 0, 1, 3, 7, 14, and 28days. Untreated rats served as CG. Histological sections were prepared and immunohistochemically stained for VEGF and bFGF. Three groups were evaluated for PDL area and the number of VEGF and bFGF immunopositive cells in PDL. The number of immunopositive cells and PDL area in CG and RG were significantly larger when compared with HG, and PDL area in RG was similar to that in CG. In the recovery process, PDL area and number of VEGF-positive cells in PDL increased from days 0 to 7 and decreased from days 7 to 28. Conversely, the number of bFGF-positive cells in PDL increased significantly after day 1 and peaked at 28days. This study suggests that occlusal stimuli regulate PDL area through expression of VEGF and bFGF in rat PDL. Occlusal stimuli are able to regulate the expression of VEGF and bFGF in PDL cells, and these growth factors may lead to alveolar bone remodeling in PDL.

Biochemical characterization of human gingival crevicular fluid during orthodontic tooth movement using Raman spectroscopy.

This study used Raman spectroscopy to report the first human gingival crevicular fluid (GCF) biochemical characterization during the early phase of orthodontic tooth movement. This technique allows for label-free and noninvasive biochemical change monitoring in GCF during orthodontic tooth movement. Ten orthodontic patients (20.8 ± 2.5 years) participated in the study. GCF samples were obtained before (baseline, 0 days) and during orthodontic treatment at 1, 7 and 28 days. For Raman spectroscopic measurement, GCF samples (5 µl) were deposited onto a gold-coated substrate, then dried at room temperature. Raman spectra GCF analysis during orthodontic treatment indicated that the hydroxyapatite to primarily collagen-dominated matrix band (phosphate 984 cm(-1)/amide I 1667 cm(-1)) intensity ratio decreased at day 7 (P < 0.05). The carbonate apatite to hydroxyapatite ratio (carbonate 1088 cm(-1)/phosphate 984 cm(-1)) was significantly higher on day 7 compared to day 0 (P < 0.05). These results indicate that demineralization occurs during the alveolar bone remodeling process. We also found notable peak shifts in the amide I range during orthodontic tooth movement. The 1658 cm(-1) in baseline red shifted to 1667 cm(-1) at orthodontic treatment day 7. Curve fitting in the amide I (1615-1725 cm(-1)) range demonstrated that increased random coil conformation was accompanied by a decrease in β-sheet structure during orthodontic tooth movement. Thus, we suggest Raman spectroscopy could be used for label-free, non-invasive GCF quality assessment during orthodontic tooth movement. Furthermore, this method may prove to be a powerful diagnostic and prognostic tool for monitoring orthodontic tooth movement in a clinical setting.

Finite element simulation of the behavior of the periodontal ligament: A validated nonlinear contact model

Due to its significance in tooth movement, the stress/deformation field of periodontium and the alveolar bone remodeling process, periodontal ligament (PDL) cannot be excluded from the studies investigating dental biomechanics regarding its excessive deformability. Therefore, many analytical and numerical researches are carried out to simulate its response and to create a constitutive model via experiments intending to discover the material properties of PDL. The aim of this study is to formulate a user specified contact model that can be used in conjunction with finite element (FE) software and reflects PDL’s influence on neighboring structures based on the currently available information, without requiring an actual volumetric finite element mesh of ligament. The results show good agreement with available experimental tooth mobility data. Smooth stress fields are obtained on the tooth root and alveolar bone, which is a significant aspect in bone-remodeling studies. The advantage of simulating PDL as a contact model at the interface of tooth root and the alveolar process instead of a solid-meshed FE model with poor geometric morphology and/or very dense mesh is expected to save pre/post-processing workforce, to increase the accuracy and to contribute to the smoothness of interface stress distributions.

Effect of occlusal hypofunction and its recovery on the three-dimensional architecture of mandibular alveolar bone in growing rats

BackgroudNormal occlusion is very important for physiological structure of mandible. However, the details of influences of occlusal hypofunction and its recovery on the three-dimensional architecture of mandibular alveolar bone in growing rats are still lacking. Materials and methodsForty-eight growing male Sprague–Dawley rats were randomly divided into normal (n = 24), hypofunctional (n = 12), and recovery (n = 12) groups. The hypofunction group was developed by inserting a bite-raising appliance between the maxillary and mandibular incisors of the rats. Two weeks after insertion, the appliance was removed to result in the recovery group; the experiment continued for two additional weeks. The experimental animals and control animals were killed weekly. In addition to measuring the body weight and masseter muscle weight of the rats, the histomorphology and microstructure of the mandibular alveolar bone were scanned using microcomputed tomography. ResultsA lighter masseter muscle and a higher and narrower alveolar process were observed in the hypofunction group compared with the control animals (P < 0.05). Mandibular remodeling also occurred in the hypofunctional group, as demonstrated by a smaller trabecular cross-sectional area, looser trabecular bone, decreased bone volume fraction, trabecular thickness, trabecular number, and increased bone surface density and trabecular separation, especially at week 2 (P < 0.05). After removing the anterior bite-opening appliance, the altered masseter muscle weight and architecture of the mandibular alveolar bone were gradually reversed and reached normal levels at the end of the experiment (P > 0.05). ConclusionsA loss of occlusal stimuli can lead into mandibular alveolar bone remodeling, and the recovery of occlusion can restore the altered mandibular architecture in growing rats.