Vibration accelerates orthodontic tooth movement by inducing osteoclastogenesis via transforming growth factor-ß signalling in osteocytes.

BACKGROUND: We previously found the conditions of supplementary vibration that accelerated tooth movement and induced bone resorption in an experimental rat tooth movement model. However, the molecular biological mechanisms underlying supplementary vibration-induced orthodontic tooth movement are not fully understood. Transforming growth factor (TGF)-ß upregulates osteoclastogenesis via induction of the receptor activator of nuclear factor kappa B ligand expression, thus TGF-ß is considered an essential cytokine to induce bone resorption. OBJECTIVES: The aim of this study is to examine the role of TGF-ß during the acceleration of orthodontic tooth movement by supplementary vibration. MATERIALS AND METHODS: In experimental tooth movement, 15 g of orthodontic force was loaded onto the maxillary right first molar for 28 days. Supplementary vibration (3 g, 70 Hz) was applied to the maxillary first molar for 3 min on days 0, 7, 14, and 21. TGF-ß receptor inhibitor SB431542 was injected into the submucosal palatal and buccal areas of the maxillary first molars once every other day. The co-culture of RAW264.7 cells and MLO-Y4 cells was used as an in vitro osteoclastogenesis model. RESULTS: SB431542 suppressed the acceleration of tooth movement and the increase in the number of osteoclasts by supplementary vibration in our experimental rat tooth movement model. Immunohistochemical analysis showed supplementary vibration increased the number of TGF-ß1-positive osteocytes in the alveolar bone on the compression side during the experimental tooth movement. Moreover, vibration-upregulated TGF-ß1 in MLO-Y4 cells induced osteoclastogenesis. CONCLUSIONS: Orthodontic tooth movement was accelerated by supplementary vibration through the promotion of the production of TGF-ß1 in osteocytes and subsequent osteoclastogenesis.

A case report of multidisciplinary treatment of an adult patient with bilateral cleft lip and palate.

This is a case report about the successful orthodontic treatment of a bilateral cleft lip and palate patient by using a combination of bone grafting and subsequent prosthodontic rehabilitation. An adult patient with a bilateral cleft lip and palate presented with a concave profile, anterior and lateral crossbite, a markedly deep overbite, and residual bilateral alveolar clefts. His jaw movement patterns were unstable and irregular due to his collapsed bite. Orthodontic treatment with bilateral bone grafting improved his concave profile by downward and backward rotation of the mandible within the freeway space, and optimum occlusion and functionally stable and smooth jaw movements were obtained. After a 6-year retention period, no skeletal relapse could be detected, and his occlusal stability was satisfactory.

Three-Dimensional Evaluation of Treatment Effects and Post-Treatment Stability of Maxillary Molar Intrusion Using Temporary Anchorage Devices in Open Bite Malocclusion.

Background: We investigated treatment outcomes and post-treatment stability in 10 patients with an anterior open bite and nonsurgical orthodontics. Methods: The patients underwent maxillary molar intrusion using temporary anchorage devices (TADs) to deepen the overbite due to mandibular autorotation. Lateral cephalograms and dental cast models were obtained before treatment (T0), immediately after it (T1), and >1 year after it (T2). Skeletal and dental cephalometric changes and three-dimensional movements of the maxillary dentitions were evaluated. Results: At T0, cephalometric analysis indicated that patients had skeletal class I with tendencies for a class II jaw relationship and a skeletal open bite. During active treatment (T0 to T1), the maxillary first molar intruded by 1.6 mm, the mandibular first molar extruded by 0.3 mm, the Frankfort-mandibular plane angle decreased by 1.1°, and the overbite increased by 4.1 mm. Statistically significant changes were observed in the amount of vertical movement of the maxillary first molar, Frankfort-mandibular plane angle, and overbite. Three-dimensional (3D) dental cast analysis revealed that the maxillary first and second molars intruded, whereas the anterior teeth extruded, with the second premolar as an infection point. In addition, the maxillary molar was tipped distally by 2.9° and rotated distally by 0.91°. Statistically significant changes were observed in the amount of vertical movement of the central incisor, lateral incisor, canine and first molar, and molar angulation. From T1 to T2, no significant changes in cephalometric measurements or the 3D position of the maxillary dentition were observed. The maxillary and mandibular dentitions did not significantly change during post-treatment follow-up. Conclusions: Maxillary molar intrusion using mini-screws is an effective treatment for open bite correction, with the achieved occlusion demonstrating 3D stability at least 1 year after treatment.

Three-dimensional morphologic analysis of the maxillary alveolar bone after anterior tooth retraction with temporary anchorage devices.

OBJECTIVES: To investigate three-dimensional (3D) morphologic changes in the alveolar bone around the maxillary central incisors of patients who underwent premolar extraction and subsequent anterior tooth retraction using temporary anchorage devices (TADs). MATERIALS AND METHODS: The subjects consisted of 16 patients with bimaxillary protrusion. The maxillary anterior teeth were retracted using sliding or loop mechanics and TADs for anchorage reinforcement. Cephalograms and computed tomography scans taken pretreatment and posttreatment were registered with respect to the palatal structures. The movement of the maxillary central incisors and morphologic changes in the anterior alveolar bone were evaluated quantitatively. RESULTS: Displacement in the palatal direction was observed in the alveolar bone around the incisors and the interdental septum. The displacement and bone remodeling/tooth movement ratio were larger on the labial side than the palatal side, and decreased progressively from the crest to apex level. The bone thickness was significantly increased on the labial side and decreased on the palatal side. CONCLUSIONS: Regional differences exist in morphologic changes of the alveolar bone during anterior tooth retraction using TADs. Attention should be paid to the crest region of the palatal alveolar bone because of its small original thickness and low remodeling activity.

The role of TRPV2 as a regulator on the osteoclast differentiation during orthodontic tooth movement in rats.

When orthodontic forces are applied to teeth, bone remodeling, which consists of bone resorption and bone formation, occurs around the teeth. Transient receptor potential vanilloid 2 (TRPV2) is a cation channel expressed in various cell types that responds to various stimuli, including mechanical stress, and involved in calcium oscillations during the early stages of osteoclast differentiation. However, in vivo expression of TRPV2 in osteoclasts has not yet been reported, and temporo-spatial expression of TRPV2 during osteoclast differentiation is unclear. In this study, we examined the TRPV2 expression during experimental tooth movement and assessed the effect of TRPV2 on osteoclast differentiation. TRPV2 was detected on day 1 after experimental tooth movement on the compression side, and the number of TRPV2-expressing cells significantly increased on day 7. These TRPV2-expressing cells had a single, or multiple nuclei and were positive for TRAP activity. Consistent with these in vivo findings, in vitro experiments using RAW264.7 osteoclast progenitor cells showed that TRPV2 mRNA was increased at the early stage of osteoclast differentiation and maintained until the late stage. Furthermore, a TRPV2 channel selective antagonist significantly inhibited osteoclast differentiation. These findings suggest that TRPV2 may have a regulatory role in osteoclast differentiation during orthodontic tooth movement.

A comparative study on cephalometric differences in maxillofacial morphology between skeletal Class III cases with and without acromegaly: a pilot study.

OBJECTIVES: The most typical maxillofacial feature of patients with acromegaly is mandibular protrusion. This study aimed to determine differences in maxillofacial morphology between skeletal Class III patients with and without acromegaly using cephalometric analysis. METHODS: Cephalograms of 37 patients with acromegaly (Acro), 37 age-matched non-acromegalic patients with skeletal Class III malocclusion (C-III), and 37 age-matched Class I malocclusion patients (C-I; control) were retrospectively collected. The skeletal and dental morphology of each group was analyzed using cephalometric analysis, which included linear and angular measurements and facial profilograms. In addition, we analyzed diagnostic performance and cutoff values for discriminating acromegaly from skeletal Class III malocclusion using receiver operating characteristic (ROC) curve analysis. RESULTS: The mandibular ramus height was larger in the Acro group than in the other groups. The increase in L1/MP in the Acro group, which represented labial inclination of the mandibular central incisors, was the most characteristic feature in this study. ROC curve analysis indicated that a cutoff value of 88.4° for L1/MP had the highest diagnostic performance in discriminating acromegaly from non-acromegalic Class III malocclusion. CONCLUSIONS: Acromegaly was characterized by a greater degree of bimaxillary prognathism than was non-acromegalic Class III malocclusion. Focusing on labial inclination of the mandibular central incisors would be the most useful way to differentiate acromegaly from non-acromegalic Class III malocclusion.

Expression of Ten-m/Odz3 in the fibrous layer of mandibular condylar cartilage during postnatal growth in mice.

It has been speculated that the mandibular condyle develops via the differentiation of the fibroblast-like cells covering the condyle into chondrocytes; however, the developmental mechanisms behind this process have not been revealed. We used laser-capture microdissection and cDNA microarray analysis to elucidate the genes that are highly expressed in these fibroblast-like cells. Among these genes, the transcription of Ten-m/Odz3 was significantly increased in the fibroblast-like cells compared with other cartilage tissues. For the first time, we describe the temporal and spatial expression of Ten-m/Odz3 mRNA in relation to the expression of type I, II, and X collagen mRNA, as determined by in-situ hybridization in mouse mandibular condylar cartilage and mouse femoral cartilage during the early stages of development. Ten-m/Odz3 was expressed in the fibrous layer and the proliferating and mature chondrocyte layers, which expressed type I and II collagen, respectively, but was not detected in the hypertrophic chondrocyte layer. Furthermore, we evaluated the in-vitro expression of Ten-m/Odz3 using ATDC5 cells, a mouse chondrogenic cell line. Ten-m/Odz3 was expressed during the early stage of the differentiation of mesenchymal cells into chondrocytes. These findings suggest that Ten-m/Odz3 is involved in the differentiation of chondrocytes and that it acts as a regulatory factor in the early stages of the development of mandibular condylar cartilage.

Delayed tooth movement in Runx2+/- mice associated with mTORC2 in stretch-induced bone formation.

Runt-related transcription factor 2 (Runx2) is an essential transcription factor for osteoblast differentiation, and is activated by mechanical stress to promote osteoblast function. Cleidocranial dysplasia (CCD) is caused by mutations of RUNX2, and CCD patients exhibit malocclusion and often need orthodontic treatment. However, treatment is difficult because of impaired tooth movement, the reason of which has not been clarified. We examined the amount of experimental tooth movement in Runx2+/- mice, the animal model of CCD, and investigated bone formation on the tension side of experimental tooth movement in vivo. Continuous stretch was conducted to bone marrow stromal cells (BMSCs) as an in vitro model of the tension side of tooth movement. Compared to wild-type littermates the Runx2+/- mice exhibited delayed experimental tooth movement, and osteoid formation and osteocalcin (OSC) mRNA expression were impaired in osteoblasts on the tension side of tooth movement. Runx2 heterozygous deficiency delayed stretch-induced increase of DNA content in BMSCs, and also delayed and reduced stretch-induced alkaline phosphatase (ALP) activity, OSC mRNA expression, and calcium content of BMSCs in osteogenic medium. Furthermore Runx2+/- mice exhibited delayed and suppressed expression of mammalian target of rapamycin (mTOR) and rapamycin-insensitive companion of mTOR (Rictor), essential factors of mTORC2, which is regulated by Runx2 to phosphorylate Akt to regulate cell proliferation and differentiation, in osteoblasts on the tension side of tooth movement in vivo and in vitro. Loss of half Runx2 gene dosage inhibited stretch-induced PI3K dependent mTORC2/Akt activity to promote BMSCs proliferation. Furthermore, Runx2+/- BMSCs in osteogenic medium exhibited delayed and suppressed stretch-induced expression of mTOR and Rictor. mTORC2 regulated stretch-elevated Runx2 and ALP mRNA expression in BMSCs in osteogenic medium. We conclude that Runx2+/- mice present a useful model of CCD patients for elucidation of the molecular mechanisms in bone remodeling during tooth movement, and that Runx2 plays a role in stretch-induced proliferation and osteogenesis in BMSCs via mTORC2 activation.

Reduction of orthodontic tooth movement by experimentally induced periodontal inflammation in mice.

Orthodontic therapy is known to have an aggravating effect on the progression of destructive periodontitis if oral hygiene is not maintained. However, it is largely unknown how active periodontitis affects the velocity of orthodontic tooth movement. In this study, we examined the effect of periodontal inflammation on orthodontic tooth movement using a mouse model. Orthodontic force was applied on the maxillary first molar of mice, with or without ligature wire to induce experimental periodontitis. The distance moved by the first molar was significantly reduced by the ligature-induced experimental periodontitis. Tartrate-resistant acid phosphatase staining revealed that the number of osteoclasts present during orthodontic treatment was lower in the pressure zone of alveolar bone in the presence of periodontal inflammation. Consistently, the expression level of receptor activator of nuclear factor-kappaB ligand (RANKL) in the pressure zone was decreased in the ligature group. By contrast, experimental periodontitis increased the expression of cyclooxygenase-2 mRNA in the periodontal tissues, while in vitro treatment with prostaglandin E(2) decreased extracellular signal-regulated kinase phosphorylation and RANKL expression induced by mechanical stress in osteoblasts. Taken together, these results suggest that the orthodontic force-induced osteoclastogenesis in alveolar bone was inhibited by the accompanying periodontal inflammation, at least partly through prostaglandin E(2), resulting in reduced orthodontic tooth movement.

Mandibular deviation and canted maxillary occlusal plane treated with miniscrews and intraoral vertical ramus osteotomy: functional and morphologic changes.

Conventionally, the combination of mandibular and maxillary osteotomy is used to correct both mandibular deviation and maxillary canted occlusal plane. This case report describes functional and morphologic changes after an alternative treatment with miniscrew anchorage instead of maxillary osteotomy. A boy, aged 16 years 5 months, had temporomandibular joint disease symptoms, facial asymmetry with mandibular deviation, and a maxillary canted occlusal plane. The maxillary molars on the right side were extruded 3 mm compared with those on the left side. In addition, there were functional problems: lopsided chewing and asymmetric motion range of the bilateral condyles. After correction of the maxillary canted occlusal plane by intrusion of the maxillary right molars with miniscrew anchorage, the mandibular deviation was corrected with mandibular osteotomy. As the therapeutic result, functional symmetry was achieved in addition to symmetric morphologic changes, suggesting that combination treatment of miniscrew anchorage and mandibular osteotomy is effective for treating patients with mandibular deviation and maxillary canted occlusal plane.

Effects of mandibular advancement plus prohibition of lower incisor movement on mandibular growth in rats.

INTRODUCTION: To test the hypothesis that mandibular advancement with the use of a fixed functional appliance combined with prohibition of labial movement of the lower incisors will have no effect on mandibular growth in growing rats. MATERIALS AND METHODS: Fifteen 4-week-old male rats were divided into fixed, unfixed, and control groups (n = 5, each). Bite-jumping appliances were used in the fixed and unfixed groups. Sites of bone perforation and the lower incisors were connected with ligature wires in the fixed group. The ramus height, mandibular length, and inclination of lower incisors were examined for 4 weeks, and those values were compared among five intervals and three groups by through one-way analysis of variance models and the Bonferroni multiple comparison test for post hoc comparison. RESULTS: Increases in ramus height and mandibular length during the experimental period were 1.5 mm and 2.5 mm in the fixed group, 1 mm and 1.5 mm in the unfixed group, and 1.2 mm and 1.9 mm in the control group, respectively. Growth of ramus height and growth of mandibular length in the fixed group were greater than in the unfixed and control groups during the experimental period. The inclination of lower incisors in the unfixed group was increased 8.0 degrees throughout the experimental period, which differed from results obtained in the other groups. CONCLUSIONS: Mandibular growth was accelerated effectively before and during the pubertal period in rats by mandibular advancement with a fixed functional appliance combined with prohibition of labial movement of the lower incisor.

Vibration enhances osteoclastogenesis by inducing RANKL expression via NF-κB signaling in osteocytes.

To shorten the duration of orthodontic treatment it is important not only to reduce risks such as dental caries, periodontal disease, and root resorption, but also to decrease pain and discomfort caused by a fixed appliance. Several studies have investigated the effect of vibration applied to fixed appliances to accelerate tooth movement. Although it was reported that vibration accelerates orthodontic tooth movement by enhancing alveolar bone resorption, the underlying cellular and molecular mechanisms remain unclear. In this study, we investigated the effects of vibration on osteoclastogenesis in vitro and in vivo. Vibration applied to pre-osteoclast cell line RAW264.7 cells enhanced cell proliferation but did not affect their differentiation into osteoclasts. Osteocytes in bone are known to be mechanosensitive and to act as receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). Therefore, in the present study, vibration was applied to cells from the osteocyte-like cell line MLO-Y4. In MLO-Y4 cells, vibration induced phosphorylation of the inhibitor of NF-κB (IκB) and caused nuclear localization of NF-κB p65. Additionally, vibration increased RANKL mRNA expression, but did not affect osteoprotegerin (OPG) mRNA expression in MLO-Y4 cells, thus resulting in an increased RANKL/OPG ratio. Consistent with these findings, vibration applied during experimental tooth movement increased NF-κB activation and RANKL expression in osteocytes on the compression side of alveolar bone in vivo, whereas vibration had no such effects on the tension side. Furthermore, in a co-culture of MLO-Y4 cells and RAW264.7 cells, vibration applied to MLO-Y4 cells enhanced osteoclastogenesis. These findings suggest that vibration could accelerate orthodontic tooth movement by enhancing osteoclastogenesis through increasing the number of pre-osteoclasts and up-regulating RANKL expression in osteocytes on the compression side of alveolar bone via NF-κB activation.

Dental and craniofacial characteristics in a patient with leprechaunism treated with insulin-like growth factor-I.

Leprechaunism is an autosomal recessive disease characterized by elfin-like faces, loss of glucose homeostasis, and severe insulin resistance. This disease is caused by inherited defects of the insulin receptor and is lethal early in life. Perhaps for this reason, the teeth and craniofacial features of patients with leprechaunism have never been reported. In the present case, the patient had been diagnosed with leprechaunism with mutation in the insulin receptor gene and had treatment with recombinant human insulin-like growth factor I (IGF-I) starting at the age of 1 year 7 months. It is of interest that all of his teeth were extremely large and subsequently showed severe crowding in the dental arches. He also showed a large tongue with an anterior open bite. He had a convex facial profile with a remarkably steep mandibular plane angle and large gonial angle. This is the first report of the characteristic phenotypes of the teeth and craniofacial morphology of a patient with leprechaunism treated with IGF-I. In addition, the possible association between these features and long-term IGF-I treatment is discussed.

Biosafety, stability, and osteogenic activity of novel implants made of Zr70Ni16Cu6Al8 bulk metallic glass for biomedical application.

Superior mechanical and chemical properties of Zr70Ni16Cu6Al8 bulk metallic glass (BMG) demonstrate its promise as a novel biomaterial for fabrication of implants. The aim of the present study was to validate mechanical, chemical, and biological properties of Zr70Ni16Cu6Al8 BMG through comparison with titanium (Ti). Our data indicated higher tensile strength, lower Young's modulus, and reduced metal ion release of Zr70Ni16Cu6Al8 BMG compared with Ti. Biosafety of bone marrow mesenchymal cells on Zr70Ni16Cu6Al8 BMG was comparable to that of Ti. Next, screw-type implant prototypes made of Zr70Ni16Cu6Al8 BMG were fabricated and inserted into rat long bones. Zr70Ni16Cu6Al8 BMG implants indicated a higher removal-torque value and lower Periotest value compared with Ti implants. In addition, higher amounts of new bone formation and osseointegration were observed around Zr70Ni16Cu6Al8 BMG implants compared with Ti implants. Moreover, gene expression analysis displayed higher expression of osteoblast- and osteoclast-associated genes in the Zr70Ni16Cu6Al8 BMG group compared with the Ti group. Importantly, loading to implants upregulated bone formation, as well as osteoblast- and osteoclast-associated gene expression in the peri-implant area. No significant difference in concentrations of Ni, Al, Cu, and Zr in various organs was shown between in the Zr70Ni16Cu6Al8 BMG and Ti groups. Collectively, these findings suggest that Zr70Ni16Cu6Al8 BMG is suitable for fabricating novel implants with superior mechanical properties, biocompatibility, stability, and biosafety compared with Ti. STATEMENT OF SIGNIFICANCE: Titanium is widely used to fabricate orthopedic and dental implants. However, Titanium has disadvantages for biomedical applications in regard to strength, elasticity, and biosafety. Recently, we developed a novel hypoeutectic Zr70Ni16Cu6Al8 BMG, which has superior mechanical and chemical properties. However, the validity of Zr70Ni16Cu6Al8 BMG for biomedical application has not been cleared. The aim of the present study was to validate the mechanical, chemical, and biological properties of Zr70Ni16Cu6Al8 BMG for biomedical applications through comparison with Titanium. The present study clarifies that Zr70Ni16Cu6Al8 BMG has good mechanical properties, corrosion resistance, and osteogenic activity, which are necessary features for biomedical applications. The present study provides for the first time the superiority of Zr70Ni16Cu6Al8 BMG implants to Titanium implants for biomedical applications.

Gene Expression Analysis of CCN Protein in Bone Under Mechanical Stress.

To investigate mechanical-dependent bone remodeling, we had previously applied various types of mechanical loading onto the teeth of rats and mice. In vitro cultured bone cells were then used to elucidate the mechanisms underlying the specific phenomenon revealed by in vivo experiments. This review describes the techniques used to upregulate CCN2 expression in bone cells produced by different types of mechanical stress, such as fluid shear stress and substrate strain in vitro, and compression or tension force in vivo.

Synergistic acceleration of experimental tooth movement by supplementary high-frequency vibration applied with a static force in rats.

Several recent prospective clinical trials have investigated the effect of supplementary vibration applied with fixed appliances in an attempt to accelerate tooth movement and shorten the duration of orthodontic treatment. Among them, some studies reported an increase in the rate of tooth movement, but others did not. This technique is still controversial, and the underlying cellular and molecular mechanisms remain unclear. In the present study, we developed a new vibration device for a tooth movement model in rats, and investigated the efficacy and safety of the device when used with fixed appliances. The most effective level of supplementary vibration to accelerate tooth movement stimulated by a continuous static force was 3 gf at 70 Hz for 3 minutes once a week. Furthermore, at this optimum-magnitude, high-frequency vibration could synergistically enhance osteoclastogenesis and osteoclast function via NF-κB activation, leading to alveolar bone resorption and finally, accelerated tooth movement, but only when a static force was continuously applied to the teeth. These findings contribute to a better understanding of the mechanism by which optimum-magnitude high-frequency vibration accelerates tooth movement, and may lead to novel approaches for the safe and effective treatment of malocclusion.

Skeletal anchorage for orthodontic correction of maxillary protrusion with adult periodontitis.

Because the number of adult patients seeking orthodontic treatment is increasing, orthodontists are becoming more likely to encounter patients with adult periodontitis. However, it is sometimes difficult to establish anchorage because of poor periodontal tissues in patients with adult periodontitis. This article reports the successful use of skeletal anchorage to treat a maxillary protrusion case complicated by severe adult periodontitis. A female patient aged 50 years seven months showed a skeletal Class II jaw base relationship. A spacing of five mm in the upper anterior teeth with an overjet of 7.5 mm and overbite of four mm was observed. She had generalized horizontal bone loss in both arches, with vertical bone loss in the posterior segment. After periodontal treatment, miniplates were placed in the zygomatic process, and retraction and intrusion of the maxillary incisors were performed. After active treatment for 21 months, the upper incisors had been inclined 9.5 degrees lingually, intruded two mm at the apex, and good anterior occlusion was achieved. Acceptable occlusion and periodontal tissue were maintained after a retention period of two years. Our results suggest that skeletal anchorage is useful for retraction and intrusion of upper incisors in cases of maxillary protrusion with severe adult periodontitis.

Connective tissue growth factor mRNA expression pattern in cartilages is associated with their type I collagen expression.

Connective tissue growth factor (CTGF) has been identified as a secretory protein encoded by an immediate early gene and is a member of the CCN family. In vitro CTGF directly regulates the proliferation and differentiation of chondrocytes; however, a previous study showed that it was localized only in the hypertrophic chondrocytes in the costal cartilages of E 18 mouse embryos. We described the expression of CTGF mRNA and protein in chondrocytes of different types of cartilages, including femoral growth plate cartilage, costal cartilage, femoral articular cartilage, mandibular condylar cartilage, and cartilage formed during the healing of mandibular ramus fractures revealed by in situ hybridization and immunohistochemistry. To characterize the CTGF-expressing cells, we also analyzed the distribution of the type I, type II, and type X collagen mRNA expression. Among these different types of cartilages we found distinct patterns of CTGF mRNA and protein expression. Growth plate cartilage and the costal cartilage showed localization of CTGF mRNA and protein in the hypertrophic chondrocytes that expressed type X collagen mRNA with less expression in proliferating chondrocytes that expressed type II collagen mRNA, whereas it was also expressed in the proliferating chondrocytes that expressed type I collagen mRNA in the condylar cartilage, the articular cartilage, and the cartilage appearing during fracture healing. In contrast, the growth plate cartilages or the costal cartilages were negative for type I collagen and showed sparse expression of CTGF mRNA in the proliferating chondrocytes. We found for the first time that CTGF mRNA could be differentially expressed in five different types of cartilage associated with those expressing type I collagen. Moreover, the spatial distribution of CTGF mRNA in the cartilages with type I collagen mRNA suggested its roles in the early differentiation, as well as in the proliferation and the terminal differentiation, of those cartilages.

Bone morphogenetic protein 3 expression pattern in rat condylar cartilage, femoral cartilage and mandibular fracture callus.

Mandibular condylar cartilage differs from primary cartilage in morphological organization of the chondrocytes and in responses to biomechanical stress and humoral factors. For the first time, we describe the expression of Bmp3 mRNA in relation to types I, II and X collagen mRNA (as determined by in situ hybridization) in chondrocytes of the rat mandibular condylar cartilage, femoral articular cartilage, femoral growth plate cartilage, and temporal cartilage, which transiently appeared in the reparative response stage of mandibular ramus fracture healing. In all cartilages evaluated, Bmp3 was expressed in proliferating chondrocytes that expressed type I collagen in condylar cartilage, articular cartilage, and temporal cartilage appearing during fracture healing. Bmp3 was also found in hypertrophic chondrocytes that expressed type X collagen mRNA in all cartilages evaluated. Furthermore, in remodeling bone, Bmp3 mRNA was strongly expressed in active osteoblast cells in periosteal reaction layers formed after fracture. These findings suggest that Bmp3 expression in a special layer of typical articular cartilage may be regulated by mechanical stress stimulation. We also found that Bmp3 was expressed in the periosteal layers of the bone segments near the fracture site during fracture healing.

Clinical assessment of orthodontic outcomes with the peer assessment rating, discrepancy index, objective grading system, and comprehensive clinical assessment.

PURPOSE: The purpose of this study was to quantitatively assess orthodontic treatment outcomes in postgraduate orthodontic clinics at Okayama University (OU) and Indiana University (IU). MATERIAL: Using the peer assessment rating (PAR) index, the discrepancy index (DI), the American Board of Orthodontist's objective grading system (OGS), and the comprehensive clinical assessment (CCA), we evaluated pretreatment and posttreatment records of 72 patients from OU and 54 patients from IU. RESULTS: The average pretreatment PAR score with United Kingdom weighting was 32 for OU subjects and 28 for IU subjects. Differences in maxillary and mandibular buccal alignment between schools were statistically significant ( P < .01). The posttreatment PAR scores were 7 for OU and 4 for IU. The difference in overjet between schools was statistically significant ( P < .05). The mean DI scores were 19 for OU and 17 for IU. OU patients scored significantly more DI points for crowding and mandibular plane angle compared with IU patients ( P < .05). On the other hand, they lost significantly fewer DI points for overbite and occlusion compared with IU patients ( P < .05). The mean OGS scores were 34 for OU and 33 for IU. Buccolingual inclination and overjet scores were significantly higher in OU patients compared with IU ( P < .05). The mean CCA score was approximately 4 points for both OU and IU. CONCLUSIONS: These data suggest that these indexes are useful for comparing treatment outcomes between clinics. They were able to identify specific problems in treating Asian patients.