The Balance between Orthodontic Force and Radiation in the Jawbone: Microstructural, Histological, and Molecular Study in a Rat Model

Irradiation of facial bones is associated with a lifelong risk of osteonecrosis. In a rat model, maxillae were exposed to a single 5 Gy dose of external beam radiation and orthodontic force was applied for 2 weeks on the first maxillary molar; control rats were treated identically without radiation. Tooth movement in irradiated jaws was 30% less than in controls, representing radiation-related damage. Micro-CT, histological, and molecular outcomes of orthodontic tooth movement were studied. Microstructurally, bone parameters (trabecular thickness, bone volume fraction, bone mineral density) were significantly affected by orthodontic force but not by radiation. Histological parameters were influenced only by orthodontic force, especially by an increase in osteoclasts. A molecular study revealed a differential distribution of cells expressing pre-osteoclast markers (RANK+—majority, CD11b+, CD14+—minority), with changes being influenced by orthodontic force (increased CD11b+ and CD14+ cells) and also by radiation (decreased RANK+ cells). The activation status of osteoclasts (TRAP staining) showed an orthodontic-force-related increase, which probably could not fully compensate for the radiation-associated impairment. The overall balance showed that orthodontic force had elicited a substantial microstructural, histological, and functional normalization process in irradiated maxillae but a radiation-induced impact was still conspicuous. Additional studies are needed to validate these findings.

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In vivo microcomputed tomography evaluation of rat alveolar bone and root resorption during orthodontic tooth movement

The Angle Orthodontist ◽

10.2319/031312-219.1 ◽

2012 ◽

Vol 83 (3) ◽

pp. 402-409 ◽

Cited By ~ 22

Author(s):

Nan Ru ◽

Sean Shih-Yao Liu ◽

Li Zhuang ◽

Song Li ◽

Yuxing Bai

Keyword(s):

Alveolar Bone ◽

Tooth Movement ◽

Root Resorption ◽

Volume Fraction ◽

Orthodontic Tooth Movement ◽

Bone Volume ◽

Structure Model ◽

Bone Volume Fraction ◽

Trabecular Thickness

ABSTRACT Objective: To observe the real-time microarchitecture changes of the alveolar bone and root resorption during orthodontic treatment. Materials and Methods: A 10 g force was delivered to move the maxillary left first molars mesially in twenty 10-week-old rats for 14 days. The first molar and adjacent alveolar bone were scanned using in vivo microcomputed tomography at the following time points: days 0, 3, 7, and 14. Microarchitecture parameters, including bone volume fraction, structure model index, trabecular thickness, trabecular number, and trabecular separation of alveolar bone, were measured on the compression and tension side. The total root volume was measured, and the resorption crater volume at each time point was calculated. Univariate repeated measures analysis of variance with Bonferroni corrections were performed to compare the differences in each parameter between time points with significance level at P < .05. Results: From day 3 to day 7, bone volume fraction, structure model index, trabecular thickness, and trabecular separation decreased significantly on the compression side, but the same parameters increased significantly on the tension side from day 7 to day 14. Root resorption volume of the mesial root increased significantly on day 7 of orthodontic loading. Conclusions: Real-time root and bone resorption during orthodontic movement can be observed in 3 dimensions using in vivo micro-CT. Alveolar bone resorption and root resorption were observed mostly in the apical third on day 7 on the compression side; bone formation was observed on day 14 on the tension side during orthodontic tooth movement.

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Antiosteoporosis Effect ofRadix ScutellariaeExtract on Density and Microstructure of Long Bones in Tail-Suspended Sprague-Dawley Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/753703 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Chen-Rui Li ◽

Guang-Wei Zhang ◽

Yin-Bo Niu ◽

Ya-Lei Pan ◽

Yuan-Kun Zhai ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Volume Fraction ◽

Bone Microarchitecture ◽

Osteoclast Differentiation ◽

Hindlimb Unloading ◽

Mineral Density ◽

Bone Volume Fraction ◽

Trabecular Thickness ◽

Radix Scutellariae

Radix Scutellariae (RS), a medicinal herb, is extensively employed in traditional Chinese medicines and modern herbal prescriptions. Two major flavonoids in RS were known to induce osteoblastic differentiation and inhibit osteoclast differentiation, respectively. This study aimed to investigate the effect ofRadix Scutellariaeextract (RSE) against bone loss induced by mechanical inactivity or weightlessness. A hindlimb unloading tail-suspended rat model (TS) was established to determine the effect of RSE on bone mineral density and bone microarchitecture. Treatment of RSE at 50 mg/kg/day and alendronate (ALE) at 2 mg/kg/day as positive control for 42 days significantly increased the bone mineral density and mechanical strength compared with TS group. Enhanced bone turnover markers by TS treatment were attenuated by RSE and ALE administration. Deterioration of bone trabecula induced by TS was prevented. Moreover, both treatments counteracted the reduction of bone volume fraction, trabecular thickness and number, and connectivity density. In conclusion, RSE was demonstrated for the first time to prevent osteoporosis induced by TS treatment, which suggests the potential application of RSE in the treatment of disuse-induced osteoporosis.

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The Incorporation of Platelet-rich Plasma into Calcium Phosphate Cement Enhances Bone Regeneration in Osteoporosis

January 2018 - Pain Physician ◽

10.36076/ppj.2014/17/e737 ◽

2014 ◽

Vol 6;17 (6;12) ◽

pp. E737-E745

Author(s):

Kyung-Hoon Kim

Keyword(s):

Bone Regeneration ◽

Trabecular Bone ◽

Volume Fraction ◽

Platelet Rich Plasma ◽

Bone Volume ◽

Filler Materials ◽

Trabecular Bone Volume ◽

Mineral Density ◽

Bone Volume Fraction ◽

Trabecular Thickness

Background: Polymethyl methacrylate (PMMA) bone cement is widely used for osteoplasty. However, previous studies have demonstrated the adverse effects of PMMA due to its excessive stiffness and heat production. Recently, calcium phosphate cement (CPC) that overcomes those negative effects has been successfully applied in osteoplasty. The potential problem of CPC is markedly less initial stiffness. It leads to progressive, repeated collapse in the treated vertebra before CPC has been replaced by new bone that would provide substantial improvement in compressive strength and stiffness. The activated platelets in platelet-rich plasma (PRP) release a high concentration of growth factors which play an important role in bone healing. Objective: To investigate whether PRP could accelerate the osteoconduction of CPC and enhance the bone strength of the treated vertebra in an animal model. Study Design: Controlled animal study. Setting: Laboratory animal study, Methods: Thirty-two female Sprague-Dawley rats were ovariectomized at 8 weeks of age. After 3 months, they were randomly divided into 4 groups and received cement augmentation in the fifth caudal spine with different filler materials; sham-operated rats (S), PMMA (P), CPC (C), and CPC + PRP (CP). Bone mineral density (BMD) and trabecular type-associated morphological parameters, including trabecular bone volume fraction and trabecular thickness in the augmented caudal spine, were evaluated by micro-computed tomography (mirco-CT) 2 weeks after the cementoplasty. Histological analysis was also performed to compare the bone regeneration. Results: The trabecular bone volume fraction in the CP group was significantly greater than those of all the other groups. Trabecular thickness was higher in the CP group than the S and P groups. This augmented trabecular structure in the CP group accordingly showed higher BMD. Histological evaluations showed significantly more bone regeneration in the CP group. Limitations: There has been a concern that the effect of PRP would be dependent on the species, and might show different results in humans. Baseline values of micro-CT analysis were not measured, which could have provided exact evidence of the changes in trabecular microarchitecture parameters and cement resorption profiles. Finally, caudal vertebrae with filler materials used in biological study should have been compared by their mechanical properties using biomechanical evaluations for a more coherent study, which was not possible due to technical problems. Conclusions: Incorporating PRP into CPC could accelerate osteoconduction in the augmented vertebra leading to improvement of trabecular bone microarchitecture and BMD in rats. Key words: Bone mineral density, calcium phosphates, cementoplasty, histology, osteoconduction, osteoporosis, platelet-rich plasma, polymethyl methacrylate, vertebra

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Comparison of the effects of three surgical techniques on the rate of orthodontic tooth movement in a rat model

The Angle Orthodontist ◽

10.2319/123016-940.1 ◽

2017 ◽

Vol 87 (5) ◽

pp. 717-724 ◽

Cited By ~ 10

Author(s):

Zachary Librizzi ◽

Zana Kalajzic ◽

Daniel Camacho ◽

Sumit Yadav ◽

Ravindra Nanda ◽

...

Keyword(s):

Rat Model ◽

Alveolar Bone ◽

Tooth Movement ◽

Volume Fraction ◽

Surgical Techniques ◽

Orthodontic Tooth Movement ◽

Tartrate Resistant Acid Phosphatase ◽

Bone Volume Fraction ◽

Bone Response ◽

Mucoperiosteal Flap

ABSTRACT Objective: To evaluate the effect of corticotomy and corticision, with and without a full mucoperiosteal flap, on the rate of tooth movement and alveolar response in a rat model. Materials and Methods: Sixty male, 6-week-old Wistar rats were divided into five groups based on surgical procedure, as follows: control (no tooth movement), orthodontic tooth movement (OTM) only, corticotomy, corticision, and corticision with full mucoperiosteal flap (corticision + flap). A force of 10–15g was applied from the maxillary left first molar to the maxillary incisors using nickel-titanium springs. Surgery was performed at the time of appliance placement (day 0), and tooth movement occurred for 21 days. Micro–computed tomography was performed on day 21 to evaluate the amount of tooth movement and alveolar bone parameters. Histomorphometry, including tartrate-resistant acid phosphatase staining, was performed to quantify the osteoclast parameters at day 21. Results: No statistical differences in the amount of OTM, bone volume fraction, and tissue density and the osteoclast parameters were found among all experimental groups. Conclusions: Corticotomy and corticision, with or without a full mucoperiosteal flap, did not show a significant effect on either the OTM magnitude or alveolar bone response.

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Effects of Leukocyte-Platelet-Rich Plasma on the Alveolar Bone Changes During Orthodontic Tooth Movement in Rabbits: A Micro-CT Study

The Journal of Indian Orthodontic Society ◽

10.1177/0301574219872608 ◽

2019 ◽

Vol 53 (4) ◽

pp. 264-271

Author(s):

Theerasak Nakornnoi ◽

Chidchanok Leethanakul ◽

Bancha Samruajbenjakun

Keyword(s):

Alveolar Bone ◽

Tooth Movement ◽

Volume Fraction ◽

Platelet Rich Plasma ◽

Orthodontic Tooth Movement ◽

Bone Volume ◽

Bone Volume Fraction ◽

Trabecular Thickness ◽

Bone Changes ◽

Trabecular Separation

Objective: To investigate the effects of leukocyte-platelet-rich plasma (L-PRP) on the alveolar bone changes at the compression and tension sides during orthodontic tooth movement. Materials and Methods: Around 20 New Zealand white rabbits were used in a split-mouth design. The maxillary first premolar was moved mesially with a nickel-titanium closed-coil spring. One side of the maxilla was randomly injected with L-PRP, while the contralateral side served as the control which received normal saline. The alveolar bone adjacent to the maxillary first premolar was scanned using microcomputed tomography at days 0, 7, 14, and 28. Microstructural parameters including bone volume fraction, trabecular thickness, and trabecular separation of alveolar bone were assessed on the compression and tension sides of the maxillary first premolar. Results: Compared between the groups, the L-PPR group showed a significantly decreased bone volume fraction on the compression side on days 7 and 14 but significantly increased bone volume fraction on the tension side on day 14. However, there were no statistically significant differences in the parameters of trabecular thickness and trabecular separation. Conclusion: Local administration of L-PRP may promote bone resorption on the compression side and bone formation on the tension side at the initial stage of orthodontic tooth movement.

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Triptolide Prevents Bone Destruction in the Collagen-Induced Arthritis Model of Rheumatoid Arthritis by Targeting RANKL/RANK/OPG Signal Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/626038 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 16

Author(s):

Chunfang Liu ◽

Yanqiong Zhang ◽

Xiangying Kong ◽

Liuluan Zhu ◽

Jian Pang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mononuclear Cells ◽

Volume Fraction ◽

Bone Destruction ◽

Signal Pathway ◽

Therapeutic Effects ◽

Mineral Density ◽

Collagen Induced Arthritis ◽

Bone Volume Fraction ◽

Trabecular Thickness

Focal bone destruction within inflamed joints is the most specific hallmark of rheumatoid arthritis (RA). Our previous study indicated that the therapeutic efficiency of triptolide in RA may be due partially to its chondroprotective and anti-inflammatory effects. However, its roles in bone destruction are still unclear. In this study, our data firstly showed the therapeutic effects of triptolide on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) mice. Then, by micro-CT quantification, triptolide treatment significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints. Interestingly, triptolide treatment could prevent the bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of NF-κB (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in sera and inflamed joints of CIA mice, which were further confirmed in the coculture system of human fibroblast-like synovial and peripheral blood mononuclear cells. These findings offer the convincing evidence for the first time that triptolide may attenuate RA partially by preventing the bone destruction and inhibit osteoclast formation by regulating RANKL/RANK/OPG signal pathway.

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Comparison of Trabecular Bone Mineral Density Measurement Using Hounsfield Unit and Trabecular Microstructure in Orthodontic Patients Using Cone-Beam Computed Tomography

Applied Sciences ◽

10.3390/app11031028 ◽

2021 ◽

Vol 11 (3) ◽

pp. 1028

Author(s):

Tae-Hyun Kim ◽

Dong-Yul Lee ◽

Seok-Ki Jung

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Volume Fraction ◽

Cervical Vertebra ◽

Hounsfield Unit ◽

Mineral Density ◽

Bone Volume Fraction ◽

Trabecular Thickness ◽

Trabecular Microstructure ◽

Trabecular Number

The aim of this study was to measure the bone mineral density of specific regions of maxilla, mandible, and first cervical vertebra using the Hounsfield unit and trabecular microstructure pattern analysis and to compare the two methods. In this study, cone-beam computed tomography (CBCT) images were obtained from 58 patients. Trabecular thickness, trabecular number, trabecular separation, and bone volume fraction were measured in 484 regions for trabecular microstructure parameters and Hounsfield unit was measured for the grayscale value. There was no difference in bone mineral density between the right and left side in every site and between males and females. Trabecular thickness and trabecular number were high in the order of anterior base of the maxilla, mandibular body, first cervical vertebra, and mandibular condyle. Bone volume fraction and Hounsfield unit were high in the order of anterior base of the maxilla, mandibular body, mandibular condyle, and first cervical vertebra (p < 0.05). Trabecular thickness, trabecular number, and bone volume fraction was positively correlated to the Hounsfield unit, and trabecular separation was negatively correlated to the Hounsfield unit (p < 0.005). This study suggests that it is possible to compare the bone mineral density of trabecular bone in various sites using the Hounsfield unit and trabecular microstructure pattern analysis.

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Evaluation of different grafting materials for alveolar cleft repair in the context of orthodontic tooth movement in rats

Scientific Reports ◽

10.1038/s41598-021-93033-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Stephan Christian Möhlhenrich ◽

Kristian Kniha ◽

Zuzanna Magnuska ◽

Benita Hermanns-Sachweh ◽

Felix Gremse ◽

...

Keyword(s):

Bone Formation ◽

Gold Standard ◽

Tooth Movement ◽

Volume Fraction ◽

Bone Substitutes ◽

New Bone Formation ◽

Mineral Density ◽

Complete Continuity ◽

Bone Volume Fraction ◽

Grafting Materials

AbstractTo minimize the postoperative risks posed by grafting autologous transplants for cleft repair, efforts are being made to improve grafting materials for use as potential alternatives. The aim of this study was to compare the bone graft quality of different bone substitutes including the gold standard autografts during the healing processes after cleft repair in the context of orthodontic treatment. In 21 Wistar rats, a complete, continuity-interrupting cleft was created. After 4 weeks, cleft repair was performed using autografts from the hips’ ischial tuberosity, human xenografts, or synthetic bone substitutes [beta-tricalcium phosphate (β-TCP)/hydroxyapatite (HA)]. After another 4 weeks, the first molar movement was initiated in the reconstructed jaw for 8 weeks. The bone remodeling was analyzed in vivo using micro-computed tomography (bone mineral density and bone volume fraction) and histology (new bone formation). All the grafting materials were statistically different in bone morphology, which changed during the treatment period. The β-TCP/HA substitute demonstrated less resorption compared to the autologous and xenogeneic/human bone, and the autografts led to a stronger reaction in the surrounding bone. Histologically, the highest level of new bone formation was found in the human xenografts, and the lowest was found in the β-TCP/HA substitute. The differences between the two bone groups and the synthetic materials were statistically significant. Autografts were confirmed to be the gold standard in cleft repair with regard to graft integration. However, parts of the human xenograft seemed comparable to the autografts. Thus, this substitute could perhaps be used as an alternative after additional tissue-engineered modification.

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MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

Journal of Dental Research ◽

10.1177/0022034520937617 ◽

2020 ◽

Vol 99 (13) ◽

pp. 1469-1477

Author(s):

J.L. Sun ◽

J.F. Yan ◽

S.B. Yu ◽

J. Zhao ◽

Q.Q. Lin ◽

...

Keyword(s):

Gene Expression ◽

Bone Loss ◽

Bone Remodeling ◽

Subchondral Bone ◽

Volume Fraction ◽

Cartilage Degradation ◽

Specific Inhibition ◽

Mineral Density ◽

Bone Volume Fraction ◽

Trabecular Thickness

Abnormal subchondral bone remodeling plays important roles during osteoarthritis (OA) pathology. Recent studies show that bone marrow mesenchymal stem cells (BMSCs) in osteoarthritic subchondral bones exhibit a prominent pro-osteoclastic effect that contributes to abnormal subchondral bone remodeling; however, the pathologic mechanism remains unclear. In the present study, we used a mouse model with OA-like change in the temporomandibular joint (TMJ) induced by an experimentally unilateral anterior crossbite (UAC) and found that the level of microRNA-29b ( miR-29b), but not miR-29a or miR-29c, was markedly lower in BMSCs from subchondral bones of UAC mice as compared with that from the sham control mice. With an intra-articular aptamer delivery system, BMSC-specific overexpression of miR-29b by aptamer-agomiR-29b rescued subchondral bone loss and osteoclast hyperfunction in UAC mice, as demonstrated by a significant increase in bone mineral density, bone volume fraction, trabecular thickness, and the gene expression of osteocalcin and Runx2 but decreased trabecular separation, osteoclast number and osteoclast surface/bone surface, and the gene expression of cathepsin K, Trap, Wnt5a, Rankl, and Rank as compared with those in the UAC mice treated by aptamer-NC (all P < 0.05). In addition, BMSC-specific inhibition of miR-29b by aptamer-antagomiR-29b exacerbated those responses in UAC mice. Notably, although it primarily affected miR-29b levels in the subchondral bone (but not in cartilage and synovium), BMSC-specific overexpression of miR-29b in UAC mice largely rescued OA-like cartilage degradation, including decreased chondrocyte density, cartilage thickness, and the percentage areas of proteoglycans and type II collagen, while BMSC-specific inhibition of miR-29b aggravated these characteristics of cartilage degradation in UAC mice. Moreover, we identified Wnt5a, but not Rankl or Sdf-1, as the direct target of miR-29b. The results of the present study indicate that miR-29b is a key regulator of the pro-osteoclastic effects of BMSCs in TMJ-OA subchondral bones and plays important roles in the TMJ-OA progression.

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Pax5 Negatively Regulates Osteoclastogenesis through Downregulation of Blimp1

International Journal of Molecular Sciences ◽

10.3390/ijms22042097 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2097

Author(s):

Jiyeon Yu ◽

Sumi Kim ◽

Nari Lee ◽

Hyoeun Jeon ◽

Jun Lee ◽

...

Keyword(s):

Bone Resorption ◽

Volume Fraction ◽

Tartrate Resistant Acid Phosphatase ◽

Mineral Density ◽

Lineage Specification ◽

Bone Volume Fraction ◽

Trabecular Thickness ◽

Negative Role

Paired box protein 5 (Pax5) is a crucial transcription factor responsible for B-cell lineage specification and commitment. In this study, we identified a negative role of Pax5 in osteoclastogenesis. The expression of Pax5 was time-dependently downregulated by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulation in osteoclastogenesis. Osteoclast (OC) differentiation and bone resorption were inhibited (68.9% and 48% reductions, respectively) by forced expression of Pax5 in OC lineage cells. Pax5 led to the induction of antiosteoclastogenic factors through downregulation of B lymphocyte-induced maturation protein 1 (Blimp1). To examine the negative role of Pax5 in vivo, we generated Pax5 transgenic (Pax5Tg) mice expressing the human Pax5 transgene under the control of the tartrate-resistant acid phosphatase (TRAP) promoter, which is expressed mainly in OC lineage cells. OC differentiation and bone resorption were inhibited (54.2–76.9% and 24.0–26.2% reductions, respectively) in Pax5Tg mice, thereby contributing to the osteopetrotic-like bone phenotype characterized by increased bone mineral density (13.0–13.6% higher), trabecular bone volume fraction (32.5–38.1% higher), trabecular thickness (8.4–9.0% higher), and trabecular number (25.5–26.7% higher) and decreased trabecular spacing (9.3–10.4% lower) compared to wild-type control mice. Furthermore, the number of OCs was decreased (48.8–65.3% reduction) in Pax5Tg mice. These findings indicate that Pax5 plays a negative role in OC lineage specification and commitment through Blimp1 downregulation. Thus, our data suggest that the Pax5–Blimp1 axis is crucial for the regulation of RANKL-induced osteoclastogenesis.

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