Expansion of the sagittal suture induces proliferation of skeletal stem cells and sustains endogenous calvarial bone regeneration.

In newborn humans, and up to approximately 2 y of age, calvarial bone defects can naturally regenerate. This remarkable regeneration potential is also found in newborn mice and is absent in adult mice. Since previous studies showed that the mouse calvarial sutures are reservoirs of calvarial skeletal stem cells (cSSCs), which are the cells responsible for calvarial bone regeneration, here we hypothesized that the regenerative potential of the newborn mouse calvaria is due to a significant amount of cSSCs present in the newborn expanding sutures. Thus, we tested whether such regenerative potential can be reverse engineered in adult mice by artificially inducing an increase of the cSSCs resident within the adult calvarial sutures. First, we analyzed the cellular composition of the calvarial sutures in newborn and in older mice, up to 14-mo-old mice, showing that the sutures of the younger mice are enriched in cSSCs. Then, we demonstrated that a controlled mechanical expansion of the functionally closed sagittal sutures of adult mice induces a significant increase of the cSSCs. Finally, we showed that if a calvarial critical size bone defect is created simultaneously to the mechanical expansion of the sagittal suture, it fully regenerates without the need for additional therapeutic aids. Using a genetic blockade system, we further demonstrate that this endogenous regeneration is mediated by the canonical Wnt signaling. This study shows that controlled mechanical forces can harness the cSSCs and induce calvarial bone regeneration. Similar harnessing strategies may be used to develop novel and more effective bone regeneration autotherapies.

A novel method for the assessment of three-dimensional tooth movement during orthodontic treatment.

OBJECTIVE: To (1) evaluate the stability of palatal rugae as landmarks for superimposition of dental casts and (2) establish a three-dimensional superimposition method of maxillary dental casts for analyzing orthodontic tooth movement. MATERIALS AND METHODS: The sample consisted of dental casts obtained from 10 patients treated with extraction of bilateral maxillary first premolars and placement of three palatal miniscrews as anchorage for retraction of the anterior teeth. Dental casts were measured by means of laser surface scanning system, and three-dimensional images were reconstructed. Serial dental casts were superimposed on the three miniscrews as registration landmarks (miniscrew-superimposition method), and the displacement of each palatal ruga point during the closure of extraction spaces was measured. Displacement of the central incisors was measured by the miniscrew-superimposition method and the proposed superimposition technique (ruga-palate-superimposition method). Correlation analysis and paired t-tests were performed to determine whether a significant difference existed between the measurements of the two superimposition methods. RESULTS: The medial points of the third palatal rugae and the shape of the palatal vault were stable throughout the treatment. The displacement of the central incisors measured using the ruga-palate-superimposition method showed no significant difference with that measured using the miniscrew-superimposition method. CONCLUSION: The maxillary dental casts can be reliably superimposed on the medial points of the third palatal rugae and the palatal vault as reference landmarks.

Effect of celecoxib on emotional stress and pain-related behaviors evoked by experimental tooth movement in the rat.

OBJECTIVE: To test the efficacy of an animal model of pain and stress and evaluate the effects of celecoxib administered when orthodontic force is applied. MATERIALS AND METHODS: A 20-g reciprocal force was applied via an orthodontic appliance to the maxillary left first and second molars of 7-week-old male Sprague-Dawley rats. Rat behavior was evaluated at 5, 24, and 48 hours after the appliance was set. Behavior was assessed in a test field by the number of lines crossed in the first 30 seconds and 5 minutes following force application; number of lines crossed to the center; rearing time; and facial grooming time. Experimental group 1 received intraperitoneal administration of 30 mg/kg celecoxib before every behavioral test. Experimental group 2 received 90 mg/kg before the first behavioral test, and physiologic saline was administered before the remaining behavioral tests. Control groups received saline before every behavioral test and were given passive (passive control group) and active (active control group) appliances, respectively. RESULTS: Parameters related to pain increased in the active controls, whereas the parameters in the experimental groups decreased to the level seen in the passive controls. Statistically significant differences in pain-related behavior between control and experimental groups were found at 5 and 24 hours after placing the appliance. Stress-related behavior was significantly less in the experimental groups compared to the active control group during experimental periods. CONCLUSIONS: The administration of celecoxib relieves pain- and stress-related behavior evoked by orthodontic tooth movement in the rat. This model might be a useful tool for the evaluation of pain and stress.

Effects of steroidal and nonsteroidal drugs on tooth movement and root resorption in the rat molar.

OBJECTIVE: To test the hypothesis that the administration of aspirin, acetaminophen, meloxicam, celecoxib, and prednisolone have no effect on root resorption and tooth movement. MATERIALS AND METHODS: A mesial force of 50 g was applied to the left maxillary first molars of sixty 10-week-old male Wistar rats using nickel titanium closed coil springs attached to the cervical area of the incisors. The rats were randomly divided into 12 groups of 5 each. High and low doses of aspirin, acetaminophen, meloxicam, celecoxib, and prednisolone were administered via drinking water for 2 weeks. The experimental control group had tooth movement but received no drug. The negative control group received neither tooth movement nor drugs. The amount of tooth movement was measured on digitized lateral cephalometric radiographs. Rats were sacrificed after 2 weeks. Mesial and distal roots (distobuccal and distopalatal) were examined using scanning electron and three-dimensional (3D) scanning laser microscopes. The surface area, depth, volume, and roughness of the root resorption craters were measured. RESULTS: When compared with experimental control rats, only prednisolone- and high-dose celecoxib-treated groups showed significantly less root resorption and less tooth movement. Although low dose celecoxib-treated group significantly decreased the tooth movement, root resorption was similar to the control group. Furthermore, resorption craters showed a smoother surface in the prednisolone-treated rats. CONCLUSIONS: The hypothesis was rejected. Administration of prednisolone and high-dose celecoxib reduces root resorption and interferes with tooth movement in rats. Both drugs may interfere in the arachidonic acid cascade depending on dose thresholds.

Application of Enamel Matrix Derivative and Intrusive Orthodontic Movement in the Treatment of Vertical Bony Defects: A Case Report.

This case report presents treatment of a severe localized horizontal bone loss combined with infrabony defects adjacent to pathologically migrated teeth by orthodontic intrusion following a graft of enamel matrix derivative (EMD) without root surface conditioning. The patient was diagnosed with Angle Class II malocclusion, anterior spacing, and pathologically migrated incisors. Graft of EMD mixed with bone materials was applied for periodontal regeneration before orthodontic treatment, and periapical radiographs were taken every 3 months for radiographic evaluation. After closure of anterior spaces by orthodontic treatment, infrabony defects improved dramatically, with a favorable alveolar bone level and periodontal pocket depth.

Emotional stress- and pain-related behaviors evoked by experimental tooth movement.

OBJECTIVE: To investigate by behavioral methods the relationship between emotional stress and pain during experimental tooth movement in rats. MATERIALS AND METHODS: Sixteen male Sprague-Dawley rats (210 to 250 g) were divided into two groups. The experimental group was treated with an active Ti-Ni appliance, and the control group received a passive appliance. A force of 20 gf was delivered by the active appliance between the maxillary first and second molars for 3 days. During this period the rat's behavior was evaluated eight times by means of open-field test and resistance-to-capture test. The specific parameters of animal activity were facial grooming, rearing, and locomotor activity, movement into the center of the open field, and response to capture. RESULTS: Parameters related to stress and pain were higher in the group carrying active appliance, compared to the group with a passive appliance. Statistically significant differences in stress-related behavior between control and experimental groups were found 8 hours after placing the appliance and were most evident on the second day. Pain-related behavior was significantly greater in the experimental group than in the control group at 24 hours. CONCLUSIONS: The increase in emotional stress evoked by orthodontic tooth movement may precede the appearance of periodontal pain.

Force magnitude and duration effects on amount of tooth movement and root resorption in the rat molar.

OBJECTIVE: To test the hypothesis that there is no difference in the effect of different continuous moderate to very heavy forces on root resorption or amount of tooth movement. MATERIALS AND METHODS: In the study, 10, 25, 50 and 100 g mesial force were applied to the maxillary first molars of rat using nickel titanium closed-coil springs for 3 days, 14 days, and 28 days. The molars were extracted and the surface areas of the root resorption craters were measured using scanning electron microscope. The depths of the root resorption craters were measured using a three-dimensional laser scanning microscope. Tooth movement of the maxillary first molar was measured in relation to the maxillary second molar on digitized lateral cephalometric radiographs. RESULTS: Three days after force application, the tooth movement was not proportionally related to force magnitude. However, 14 days of force application resulted in significantly more tooth movement in the 10, 25, and 50 g force groups than in the 100 g force group. A force application of 10 g produced significantly more tooth movement at 28 days than all the other three force applications. The largest and deepest resorption craters were observed in the disto-buccal root followed by disto-palatal, middle-buccal, middle-palatal, and mesial root. Root resorption and tooth movement increased over time from 3 to 28 days. As heavier forces were applied, greater root resorption occurred. CONCLUSION: The hypothesis is rejected. The light mesially oriented forces, as applied in this study, produced more tooth movement and less root resorption compared with heavier forces.

Comparison of jaw-opening reflexes evoked by Er:YAG laser versus scalpel incisions in rats.

OBJECTIVE: Anecdotal remarks suggest that incisions in oral soft tissue would be less painful if performed with laser rather than with scalpel, but such an argument remains to be scientifically validated. STUDY DESIGN: Twelve rats received graded incisions to lip, gingiva, mucosa, and tongue with either a pulsed Er:YAG laser (65 mJ/pulse at 10 Hz) or a stainless steel scalpel. The amplitude of the jaw-opening reflex, as measured by the digastric muscle electromyogram, was used to quantify the nociceptive response evoked by the surgical incisions. RESULTS: Except for lip, mean reflex amplitudes evoked by laser were significantly smaller (P < .05) than those evoked by scalpel in all other incision sites. CONCLUSION: Er:YAG laser surgery may be less painful and therefore require less use of anesthesia and sedation than conventional scalpel surgery in oral soft tissue procedures.