Tatsuo Kawamoto

Experimental Tooth Movement Into Bone Induced by Recombinant Human Bone Morphogenetic Protein-2

OBJECTIVE The development of biomaterials for secondary bone grafting to the alveolar cleft, recombinant human morphogenetic protein-2 (rhBMP-2) may have great potential to promote osseous regeneration. The purpose of this study was to investigate the osteoinductive activity of low-dose rhBMP-2 (10 microg/100 microL) and the biological response of newly generated bone to orthodontic stimulation, compared with previous results using high-dose rhBMP-2 (40 microg/100 microL). METHOD After extraction of the maxillary first premolars, bone defects were surgically created in eight adult beagle dogs using a 5-mm-diameter trepan bar. The rhBMP-2 with a PLGA/gelatin sponge complex (PGS) made of gelatin and polylactic acid polyglycolic acid copolymer was immediately implanted. The osteoinductive activity of rhBMP-2 and tooth movement into the newly generated bone was evaluated based on histological and morphometric examination. RESULTS Dramatic histological and morphometric differences were found in the time course of bone remodeling between low- and high-dose rhBMP-2. The onset of bone remodeling occurred significantly earlier in low-dose rhBMP-2. During experimental tooth movement, in contrast to high-dose rhBMP-2, with which root resorption occurred, only partial cementum resorption occurred on the pressure side with low-dose rhBMP-2. CONCLUSION These results indicated that the proper dosage of rhBMP-2 should be determined for successful clinical application.

A HISTOLOGICAL STUDY ON EXPERIMENTAL TOOTH MOVEMENT INTO BONE INDUCED BY RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 IN BEAGLE DOGS

OBJECTIVE The purpose of this preliminary study was to examine experimental tooth movement into newly generated bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2). METHOD After extraction of the maxillary first premolars, bone defects were surgically created in eight adult beagle dogs using a 5-mm-diameter trepan bar. According to which material was grafted into the bone defects, animals were divided into the following four groups: (1) the rhBMP-2 group in which rhBMP-2 with a poly[ D,L-(lactide-co-glycolide)]/gelatin sponge complex was implanted; (2) the spongiosa group in which spongiosa from the tibia was grafted; (3) the nongrafted group in which no material was embedded; and (4) the control group in which only tooth extraction was performed. The osteoinductive activity of rhBMP-2 and tooth movement into the newly generated bone were examined by histological and morphometric comparisons of each group. RESULTS Considerable new bone formation was observed at the grafted site both in the rhBMP-2 and in the spongiosa groups. The area of generated bone in the rhBMP-2 group was significantly greater than that in the spongiosa group. Newly generated bone, in both the rhBMP-2 and spongisosa groups, showed a similar histological response to orthodontic force as in normal alveolar bone in the control group. However, root resorption occurred on the pressure side in the rhBMP-2 group. CONCLUSION These results indicated that rhBMP-2 might constitute an alternative material to autogeneous bone grafting for alveolar cleft defects. Further studies regarding tooth movement into generated bone induced by rhBMP-2 are suggested.

A case of oculo-facio-cardio-dental syndrome with integrated orthodontic-prosthodontic treatment.

Objective Oculo-facio-cardio-dental (OFCD) syndrome is a very rare condition that requires comprehensive dental management because of associated multiple dental anomalies such as canine radiculomegaly, delayed dentition, oligodontia, persistent primary teeth, microdontia, and macrodontia. This report presents a case of OFCD in a Japanese girl (13 years 1 month old). We analyzed cephalograms, panoramic roentgenograms, and dental casts and discuss our integrated orthodontic-prosthodontic treatment. Design The sizes of the tooth crown and root as well as lateral cephalograms were compared with those from a Japanese control group. The outcome of orthodontic treatment was evaluated by comparing cephalograms taken before and after treatment. Results Radiculomegaly was found not only in the upper and lower canines but also the upper central incisors and lower first premolars. Macrodontia was found in the upper central incisors, upper canines, lower canines, and lower first premolars. Microdontia was found in the upper lateral incisor. Lateral cephalometric analysis showed a remarkable hypoplastic midface in both the sagittal and vertical dimensions, coupled with a significantly decreased cranial base length and an increased gonial angle. Serial lateral cephalograms during orthodontic treatment from 13 to 23 years of age demonstrated only slight maxillary growth and significant downward mandibular growth with clockwise rotation in addition to pronounced labial tipping of the upper central incisors. Conclusions Characteristic dental anomalies together with a unique craniofacial dysmorphology were clarified. Successful oral rehabilitation was achieved by integrated orthodontic-prosthodontic treatment.

Three-dimensional analysis of lower lip movement during articulation in subjects with mandibular prognathism

Abstract Objective The aim of this study was to investigate lower lip movement during articulatory tasks using a three-dimensional video-based system in subjects with mandibular prognathism. Materials and methods Ten subjects with mandibular prognathism (mean age: 25.4 years) and 20 volunteers (mean age: 27.8 years) participated in the study. The target sounds used were five vowels (/a/, /i/, /u/, /e/ and /o/). The motion of black foam balls placed on four canthal points and four lip points was tracked using two video cameras with a three-dimensional analysis system for animated images. After three-dimensional coordinates were established using the canthal points to correct head motion, lip movement was measured with reference to the coordinates. The standardized trajectory for each point was computed. By comparing the standardized trajectories, differences in lower lip movement between subjects and controls were examined. The Mann–Whitney U-test was used to determine the differences in the maximum displacement of movement between the groups. Results The results showed that (1) the trajectory of lower lip movement in subjects differed to some extent in all vowels and (2) there were significant differences in the amount of lower lip movement between subjects and controls. Conclusions These results suggest that (1) lower lip movement during articulation was affected in subjects with mandibular prognathism and (2) the present method is feasible for the clinical three-dimensional analysis of lower lip movement.

Tooth eruption into the newly generated bone induced by recombinant human bone morphogenetic protein-2.

OBJECTIVE The purpose of this study was to observe tooth eruption pattern into the newly generated bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2). METHOD Three 12-week-old beagle dogs were used. Following wound healing of the extracted maxillary third deciduous incisor at the age of 13 weeks, a resection of maxillary alveolar bone (8 mm by 8 mm by 8 mm) was carried out, accompanied by extraction of the maxillary second incisor tooth germ. The rhBMP-2 (5 microgram/100 microL or 10 microgram/100 microL) was implanted in the resected area. A group that was not implanted after resection and a nonresected group were used as controls. Serial changes of the eruption pattern of the maxillary third incisor in the implanted area were observed radiographically. Oxytetracycline and calcein were employed as bone markers. Nine weeks after the implantation, the animals were sacrificed. The samples were observed histologically and analyzed using peripheral quantitative computerized tomography to acquire the bone mineral density (BMD). RESULTS In the rhBMP-2 (5 microgram/100 microL)-treated group, histological findings and the BMD of the newly generated bone were almost same as in the nonresected group. The maxillary third incisor erupted through the implanted area. However, in the rhBMP-2 (10 microgram/100 microL)-treated group, more osteoinductive activity and significantly higher BMD were observed in the newly generated bone. The maxillary third incisor erupted mesially so as to avoid this implanted area. CONCLUSION Results showed that bone remodeling and tooth eruption through the newly generated bone appear to be dose dependent. Accordingly, proper dosage of rhBMP-2 should be determined for successful clinical application.

Three-dimensional analysis of hard and soft tissue changes in patients with facial asymmetry undergoing 2-jaw surgery

OBJECTIVE We studied 3-dimensionally how hard and soft tissues of patients with facial asymmetry were changed by 2-jaw surgery. STUDY DESIGN Nine patients diagnosed with mandibular prognathism and facial asymmetry who underwent 2-jaw surgery were enrolled. Three-dimensional (3-D) computed tomographic images taken before and after surgery were superimposed by 3-D imaging software. Linear and angular measurements of hard and soft tissues were performed and compared before and after surgery. RESULTS Along with improved roll rotations of the hard and soft tissues of the facial structures by surgery, both hard and soft tissue mentons were moved toward the nonshifted side. Only the hard tissue mentons, however, were important for improving the roll rotation of the mandible. Variations in the wing of the nose and lip were significant for shaping the maxilla. CONCLUSIONS The 3-D analysis in this study enabled us to understand hard and soft tissues quantitatively, thereby providing helpful information for treatment planning.

Relaxin receptors 1 and 2 and nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) mRNAs are expressed in oral components of developing mice.

OBJECTIVE Relaxin is a pleiotropic hormone of the insulin-like peptide hormone family that plays an important role in reproductive physiology as well as in fibrosis, angiogenesis, and bone remodelling. It binds to the relaxin family peptide receptors 1 and 2 (Rxfp1 and Rxfp2) and can, in addition and independently, bind and activate the glucocorticoid receptor Nr3c1. Despite the wide-ranging effect of relaxin, the expression patterns of Rxfp1 and 2 during facial development have not been examined. In this study, we aimed to identify the mRNA expression patterns of Rxfp1, Rxfp2, and Nr3c1 in oral tissues during late mouse facial development in order to pinpoint the structures that could be sensitive to relaxin signalling during this period. DESIGN Rxfp1, Rxfp2, and Nr3c1 mRNAs were identified by in situ hybridization using digoxigenin-labelled riboprobes on coronal sections of mouse heads from embryonic days 13.5 to 18.5. RESULTS We found that Rxfp1, Rxfp2, and Nr3c1 mRNAs were expressed on the developing maxilla and mandible, Meckels cartilage, tongue, and tooth primordia between embryonic days 13.5-18.5. CONCLUSIONS Receptors that bind relaxin were present in developing oral tissues of mice. This finding suggests that relaxin may be involved in the prenatal development of the face.

RELAXIN enhances differentiation and matrix mineralization through Relaxin/insulin-like family peptide receptor 2 (Rxfp2) in MC3T3-E1 cells in vitro.

RELAXIN (RLN) is a polypeptide hormone of the insulin-like hormone family; it facilitates birth by softening and widening the pubic symphysis and cervix in many mammals, including humans. The role of RLN in bone metabolism was recently suggested by its ability to induce osteoclastogenesis and activate osteoclast function. RLN binds to RELAXIN/INSULIN-LIKE FAMILY PEPTIDE 1 (RXFP1) and 2 (RXFP2), with varying species-specific affinities. Young men with mutated RXFP2 are at high risk for osteoporosis, as RXFP2 influences osteoblast metabolism by binding to INSULIN-LIKE PEPTIDE 3 (INSL3). However, there have been no reports on RLN function in osteoblast differentiation and mineralization or on the functionally dominant receptors for RLN in osteoblasts. We previously described Rxfp1 and 2 expression patterns in developing mouse oral components, including the maxillary and mandibular bones, Meckels cartilage, tongue, and tooth primordia. We hypothesized that Rln/Rxfp signaling is a key mediator of skeletal development and metabolism. Here, we present the gene expression patterns of Rxfp1 and 2 in developing mouse calvarial frontal bones as determined by in situ hybridization. In addition, RLN enhanced osteoblastic differentiation and caused abnormal mineralization and extracellular matrix metabolism through Rxfp2, which was predominant over Rxfp1 in MC3T3-E1 mouse calvarial osteoblasts. Our data suggest a novel role for Rln in craniofacial skeletal development and metabolism through Rxfp2.

Long-term orthodontic and surgical treatment and stability of a patient with Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome (BWS) is a congenital growth disorder. Children born with BWS develop enlarged organs, including the tongue, a large body, and other signs. A woman with BWS was treated and followed for 30 years. Treatment consisted of tongue reduction, orthopedic and orthodontic treatment, orthognathic surgery, and retention. The patient was first treated when she was 5 years old. Her original orthodontic problems included macroglossia, anterior open bite, anterior crossbite, and a skeletal Class III jaw relationship caused by significant mandibular protrusion. The jaw-base relationships did not improve in the early preadolescent period after phase 1 of orthodontic treatment with a vertical chincap. With the growth spurt accompanying puberty, she developed a severe skeletal Class III jaw relationship and a constricted maxillary arch. Surgically assisted rapid maxillary expansion was performed at 23 years of age to correct the severe discrepancy between the maxillary and mandibular dental arch widths. Then, at 26 years, a LeFort I osteotomy, a horseshoe osteotomy, a bilateral sagittal split ramus osteotomy, and genioplasty were performed after presurgical orthodontic treatment with extraction of the mandibular first molars. Both the facial profile and the occlusion were stable after 6 years of retention. This case report discusses the result of long-term observation of a patient with BWS who underwent tongue reduction, early orthodontic treatment, and surgical-orthodontic treatment.

The Effects of Hyperbaric Oxygen on Tooth Movement Into the Regenerated Area After Distraction Osteogenesis

Objective To analyze the effect of hyperbaric oxygen on newly formed bone in distracted areas surrounding the root of a moving tooth by histological and radiological analysis. It was hypothesized that the application of hyperbaric oxygen to a tooth moving into the distracted area would accelerate ossification and vascularization of newly formed bone in the distracted space. Design Ten dogs were used. After creating a 10-mm-long bone defect, a bony segment was prepared and translocated into the defect area at a rate of 1 mm/d for 10 days. Following the distraction period, tooth movement was started and the dogs were divided into two groups. The HBO group received hyperbaric oxygen; whereas, the control group did not. At 150 days after tooth movement, the distracted area around the moving tooth was evaluated radiologically and histologically. Differences between groups were confirmed by a Mann-Whitney U test. Results Trabecular bone density and cortical and subcortical bone areas measured by peripheral quantitative computed tomography in the HBO group were significantly higher than those in the control group. Histological observations revealed regenerated bone and blood vessels formation in the tension site of the moving tooth in the HBO group. The regenerated bone structure measured by bone histomorphometry was larger and more active in bone formation in the HBO group than in the control group. Conclusions Applying hyperbaric oxygen to tooth movement into a distracted area appears to accelerate ossification and vascularization of regenerated bone in the that area.