Upward Advancement of the Nasolabial Components at Unilateral Cleft Lip Repair Prevents Postoperative Long Lip.

OBJECTIVE: To prevent the occurrence of postoperative long lip, longitudinal postoperative changes in nasolabial forms of patients with unilateral cleft lip who underwent primary lip repair with or without upward advancement of the nasolabial components were compared. PATIENTS: Forty-three subjects (24 unilateral cleft lip and palate [UCLP] and 19 unilateral cleft lip solely, and cleft lip and alveolus [UCL/UCLA]) who underwent primary lip repair with upward advancement of the nasolabial components (NA group) and 30 subjects (16 UCLP and 14 UCL/UCLA) without upward advancement (LA group) were enrolled. OUTCOME MEASURES: Postoperative photos taken at 1 and 6 months and at 1, 2, and 3 years were used for measuring the heights of the nasal alar base (NBH), the columellar base (CBH), Cupid's peak (CPH), and the upper lip (ULH). The ratios of these measurements between the affected and unaffected sides were calculated in both groups. RESULTS: In the LA group, the 3-year postoperative all-items ratios of UCLP were significantly larger than those at 1 month postoperatively, demonstrating drooping of the nasolabial tissues in the affected side (all P < .01). Furthermore, the 3-year postoperative CPH and ULH ratio of UCL/UCLA was significantly larger than that at 1 month postoperatively, demonstrating the long lip (P < .01). In the NA group, the NBH, CBH, and CPH ratios of both UCLP and UCL/UCLA did not show significant differences between 1 month and 3 years postoperatively. CONCLUSION: Upward advancement of the nasolabial components prevents postoperative long lip.

Fifteen-Year Follow-Up Results of Presurgical Orthopedics Followed by Primary Correction for Unilateral Cleft Lip Nose in Program SEHATI in Indonesia.

Objective : To assess long-term effects of nasal correction in infancy on nasal form and growth in patients with unilateral cleft lip, alveolus, and palate (UCLP). Design : Retrospective longitudinal study. Patients : Seventeen patients with complete UCLP treated in Program SEHATI in Harapan Kita Children and Maternity Hospital, Indonesia, and followed for approximately 15 years were enrolled. Interventions : Subjects received presurgical orthopedics using a Hotz's plate and simultaneous primary lip and nose repair in which the lower lateral cartilage was repositioned through a reverse-U incision. Main Outcome Measures : Preoperative and postoperative nasal forms, including the nostril height and width ratio, the ratio of the height of the top of the alar groove, and the ratio of nostril surface areas were analyzed using color photos taken serially. One-way analysis of variance was used for statistical analyses. Results : The nostril height and width ratio and the height of the alar groove were significantly improved postoperatively and maintained for 15 years. The mean ratio of nostril surface areas was 1.01 ± 0.12 fifteen years postoperatively, and there was no significant difference from the ratio 1 year postoperatively. The major persistent deformities were septal deviation and a small skin web on the nostril rim. Conclusions : Our primary cleft lip nose correction has provided an acceptable nose form and absence of disturbance of the nasal growth in patients with UCLP. However, the repositioning of the nasal cartilage at infancy might not eliminate the need for secondary correction after puberty.

Longitudinal study of effect of Hotz's Plate and lip adhesion on maxillary growth in bilateral cleft lip and palate patients.

OBJECTIVE: To investigate the effects of infant orthopedic treatment and lip adhesion on maxillary growth of patients with bilateral cleft lip and palate (BCLP). DESIGN: Prospective longitudinal study. SETTING: The present study was conducted at the Cleft Lip and Palate Center, Harapan Kita Children and Maternity Hospital, Indonesia, and the Department of Oral and Maxillofacial Surgery, Kyushu University Hospital, Japan. SUBJECTS: The study sample consisted of 53 patients with complete BCLP and 10 noncleft patients with other diseases. Patients with BCLP were divided into three groups: H (-), 11 patients treated without Hotz's plate; H (+), 24 treated with Hotz's plate; and LA-H, 18 treated with lip adhesion and Hotz's plate. METHODS: Serial dental casts were obtained from each BCLP child at the following four time points: first visit, labioplasty, palatoplasty, and 5 years of age. Each maxillary dental cast was scanned, and the linear and angular dimensions were measured. RESULTS AND CONCLUSION: Lip adhesion showed a temporary negative effect. In all patients with BCLP, the surgeries affected the growth of the anterior arch width until the age of 5 years. Collapse of the premaxilla following labioplasty in the H (-) group affected the growth of dental arch length until the age of 5 years. Treatment using Hotz's plate prevented collapse of the premaxilla, and the growth of the arch length was comparable to that observed in the noncleft group.

Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression in tumor cells.

Anti-angiogenic therapy is a newly developed treatment method for malignant tumors. Endostatin has an anti-angiogenetic effect. Endostatin has also been shown to block the growth and metastasis of various cancers through the vascular system. However, there have so far been few reports on the relationship between endostatin and lymph node metastasis. In this study, we investigated the relationship between endostatin and the inhibition of lymph node metastasis. We first made recombinant adenovirus which expressed endostatin gene (Ad-end), and then performed the following experiments. Our findings showed Ad-end to inhibit the proliferation and tube formation of endothelial cells in vitro. In addition, Ad-end inhibited the growth of a human oral squamous cell carcinoma cell line (SQUU-B) implanted subcutaneously in the right flank of nude mice and orthotopically in the tongue of nude mice, and Ad-end also inhibited lymph node metastasis in orthotopic implantation. The number of CD31-positive blood vessels and 5'-nase-positive lymphatic vessels around Ad-end-infected tumors in tongue lesions was significantly lower than that in the control group. The down-regulation of vascular endothelial growth factor C (VEGF-C) in Ad-end-infected SQUU-B cells was recognized by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. These findings suggested that endostatin inhibited lymphangiogenesis and lymph node metastasis by suppressing the production of VEGF-C in tumor cells.

TNF inhibited the apoptosis by activation of Akt serine/threonine kinase in the human head and neck squamous cell carcinoma.

Tumour necrosis factor (TNF) is known to induce apoptosis, but recently, TNF was shown to promote cell survival, a process regulated by phosphatidylinositol-3-OH kinase (PI3K) and the NFkappaB pathway. In this study, we investigated the relationship between the molecules implicated in regulating TNF-induced cell survival and apoptosis induced by TNF in a human head and neck squamous cell carcinoma cell line (SAS), with special reference to the Akt pathway, one of the pathways related to cell survival. In SAS cells, TNF induced the phosphorylation of Akt at both Ser473 and Thr308, causing the activation of Akt, and also induced the phosphorylation and degradation of IkappaB (inhibitor of NFkappaB). This phosphorylation and degradation was inhibited by pretreating the cells with the PI3K inhibitors, wortmannin or LY294002. The apoptosis of SAS cells induced by TNF was dependent on the concentration: a high concentration of TNF, but not a low concentration, induced apoptosis within 30 h. However, a low concentration of TNF in the presence of wortmannin or LY294002 induced apoptosis. Furthermore, expression of the kinase-negative form of Akt, IKKalpha or IKKbeta, and the undegradable mutant of IkappaB, also induced apoptosis at low concentrations of TNF. When the SAS cells expressed constitutively activated Akt, apoptosis was not induced, even by high concentrations of TNF. These observations suggest that, in the SAS cell line, the PI3K-NFkappaB pathway contributes to TNF-induced cell survival and that inhibition of this pathway accelerates apoptosis.

TNFalpha played a role in induction of Akt and MAPK signals in ameloblastoma.

Tumour necrosis factor alpha (TNFalpha) is known crucial in inducing cell survival, proliferation, differentiation, and apoptosis. In the present study, we found that TNFalpha as well as its receptors, TNFR1 (TNF Receptor 1) and TNFR2, were clearly expressed in ameloblastoma tissues and AM-1 cells. By stimulation of TNFalpha in AM-1 cells, the phosphorylation of Akt (Ser473) and p44/42 mitogen-activated protein kinase (MAPK) (Thr202/Tyr204) was markedly increased in TNFalpha concentration and time dependent manner. Pretreatment with U0126, mitogen-activated extracellular-regulated kinase (MEK) 1/2 inhibitor, prior to TNFalpha stimulation, specifically inhibited TNFalpha-induced phosphorylation of p44/42 MAPK (Thr202/Tyr204) in AM-1 cells. Meanwhile, pretreatment with LY294002, phosphatidylinositol-3-OH kinase (PI3K) inhibitor, could inhibit both TNFalpha-induced phosphorylation of Akt (Ser473) and p44/42 MAPK (Thr202/Tyr204). These results suggested that TNFalpha is expressed in ameloblastoma and it can induce Akt and p44/42 MAPK activation through PI3K, which later might induce cell survival and proliferation in ameloblastoma.

Clinical significance of cellular distribution of moesin in patients with oral squamous cell carcinoma.

PURPOSE: Moesin is a linking protein of the submembraneous cytoskeleton and plays a key role in the control of cell morphology, adhesion, and motility. The aim of the present study was to elucidate the clinical significance of expression patterns of moesin in patients with oral squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: Immunohistochemistry for moesin monoclonal antibody was performed on 103 paraffin-embedded specimens from patients with primary OSCC, including 30 patients with locoregional lymph node metastasis, and in the sections from nude mice transplanted with two cell lines derived from a single human tongue cancer (SQUU-A and SQUU-B). RESULTS: Expression patterns of moesin in OSCCs were divided into three groups: membranous pattern; mixed pattern; and cytoplasmic pattern. These expression patterns correlated with tumor size, lymph node metastasis, mode of invasion, differentiation, and lymphocytic infiltration. In about two-thirds of the patients with metastatic lymph node, homogeneous cytoplasmic expression was detected in the metastatic lymph nodes. In addition, SQUU-B with high metastatic potential showed more reduced levels of membrane-bound moesin than SQUU-A with low metastatic potential. A multivariate analysis demonstrated that expression patterns of moesin can be an independent prognostic factor. CONCLUSIONS: Our results suggest that moesin expression contributed to discriminating between patients with the potentiality for locoregional lymph node metastasis and those with a better prognosis and might improve the definition of suitable therapy for each.

Mutational analysis of residues in two consensus motifs in the active sites of cathepsin E.

Cathepsin E, an intracellular aspartic proteinase of the pepsin family, is composed of two homologous domains, each containing the catalytic Asp residue in a consensus DTG motif. Here we examine the significance of residues in the motifs of rat cathepsin E by substitution of Asp98, Asp283, and Thr284 with other residues using site-directed mutagenesis. Each of the mutant proenzymes, as well as the wild-type protein, was found in culture media and cell extracts when heterologously expressed in human embryonic kidney 293T cells. The single mutants D98A, D283A, and D283E, and the double mutants D98A/D283A and D98E/D283E showed neither autocatalytic processing nor enzymatic activities under acidic conditions. However, the D98E and T284S mutants retained the ability to transform into the mature forms, although they exhibited only about 13 and 40% of the activity of the wild-type enzyme, respectively. The K(m) values of these two mutants were similar to those of the wild-type enzyme, but their k(cat) values were greatly decreased. The K(i) values for pepstatin and the Ascaris pepsin inhibitor of the mutants and the wild-type enzyme were almost the same. The circular dichroism spectra of the two mutants were essentially the same as those of the wild-type enzyme at various pH values. These results indicate that (i) Asp98, Asp283, and Thr284 are indeed critical for catalysis, and (ii) the decrease in the catalytic activity of D98E and T284S mutants is brought about by an effect on the kinetic process from the enzyme-substrate complex to the release of the product.

Central acinic cell carcinoma of the mandible. Case report.

Central acinic cell carcinoma (of the mandible) is rare, and, to our knowledge, only seven cases of this disease have been reported in the literature. A case in a 67-year-old Japanese woman is presented. Clinical examination revealed a 10.0x6.0mm mass located on the buccal aspect of the gingiva of the second molar in the left mandible. Radiographic examination revealed a radiolucency from the second to the third molar of the left mandible. Computed tomography disclosed destruction of the lingual cortical bone of the third molar region. The preliminary diagnosis was of odontogenic tumour. The patient was admitted, and removal of the tumour and of the involved teeth were carried out. Histological examination disclosed the diagnosis of acinic cell carcinoma. Subsequently, the tumour area was widely excised from the second premolar region to the coronoid process, and radical neck dissection was performed. A lymph node metastasis was found in the submandibular region. No recurrence or metastasis was observed during the 34-month follow-up.

Comparison of long-term results between different approaches to ameloblastoma.

OBJECTIVE: The long-term results of different surgical approaches to ameloblastoma were compared to develop a more rational surgical approach to this tumor. STUDY DESIGN: Seventy-eight primary ameloblastomas, including 27 unicystic, 21 multicystic, and 30 solid-type tumors, were examined in this study. The methods of treatment consisted of radical surgery (ie, resection-both segmental and marginal) and conservative treatments (ie, marsupialization alone, marsupialization followed by enucleation with sufficient bone curettage if necessary, and enucleation with bone curettage). The effect of marsupialization on recurrence data after a follow-up period of at least 5 years was evaluated with respect to clinical type and histologic pattern. RESULTS: Marsupialization was performed in 31 cystic ameloblastomas before surgery, and the effective rate of marsupialization was 74.2%. Recurrence was observed in 7.1% (3/42) after radical surgery and in 33.3% (12/36) in conservative treatments. Relatively higher tendencies of recurrence were observed in the multicystic type and follicular and/or plexiform pattern tumors. CONCLUSIONS: Conservative treatments including marsupialization and enucleation followed by sufficient bone curettage were thought to be useful, reducing the need for jaw resection. This result extends the indications for conservative treatment of ameloblastoma.

Marsupialization for odontogenic keratocysts: long-term follow-up analysis of the effects and changes in growth characteristics.

OBJECTIVE: This study evaluated the effects of marsupialization on odontogenic keratocysts (OKCs) and its role in conjunction with enucleation and curettage. STUDY DESIGN: Twenty-eight primary OKCs, treated by marsupialization before enucleation and curettage, were examined in this study. The effect of marsupialization and recurrence data after a follow-up period of at least 3 years were evaluated. The changes of growth characteristics during marsupialization were analyzed by means of histopathologic and immunohistochemical studies with monoclonal anti-Ki-67 antibody. RESULTS: The effect of marsupialization was evaluated as extremely effective (64.3%), moderately effective (32.1%), and poorly effective (3.6%). In 5 lesions, the cysts disappeared macroscopically and further surgery was not done. Recurrence was observed in 6 lesions (21.4%), and there was no significant difference in recurrence rates between the lesions treated with or without marsupialization. There appeared to be a predilection for recurrence in the lesions in the mandibular ramus region and also for radiographically multilocular lesions. Microscopic examination showed substantial changes from a parakeratinized or orthokeratinized epithelium into a hyperplastic, stratified, nonkeratinizing squamous epithelium after marsupialization in many cases. There was no significant difference in labeling index between premarsupialization (20.2% +/- 12.0%) and postmarsupialization (15.3% +/- 10.3%). CONCLUSION: Marsupialization was found to be effective as a preliminary treatment for large OKCs. This procedure does not appear to affect the recurrence tendency of OKCs, and the probable changes in growth characteristics become rather less aggressive.

The correlation of histologic features with a panoramic radiography pattern and a computed tomography pattern of bone destruction in carcinoma of the mandibular gingiva.

OBJECTIVE: We sought to clarify the correlation among a computed tomography (CT) or a panoramic radiography (PR) pattern of bone destruction, a histologic pattern of bone destruction, and a mode of invasion in carcinoma of the mandibular gingiva. STUDY DESIGN: CT images, panoramic radiographs, and decalcified, hematoxylin-eosin-stained preparations of the excised mandibular bone of 62 patients with carcinoma of the mandibular gingiva were retrospectively evaluated. Each computed tomograph, panoramic radiograph, and the histologic pattern of bone destruction was classified as 1 of 5 types: erosive, erosive and partly mixed, mixed, mixed and partly invasive, or invasive. The mode of invasion of the tumor was also assessed with a hematoxylin-eosin-stained preparation of the initial biopsy specimen. The relationships among the CT pattern, the PR pattern, the histologic pattern of bone destruction, and the mode of invasion of the tumor were statistically analyzed by using the Spearman rank correlation test. RESULTS: The CT pattern (P =.005) and the PR pattern (P =.003) were significantly correlated with the histologic pattern with respect to the bone destruction. The CT pattern (P =.996), the PR pattern (P =.997), and the histologic pattern (P =.521) of bone destruction were not correlated with the mode of invasion seen in the biopsy specimen. CONCLUSION: The CT pattern and the PR pattern of bone destruction reflect the histologic pattern of bone destruction caused by carcinoma of the mandibular gingiva but are not associated with the mode of invasion of the tumor.

[A study of the feasibility and efficacy of fetal surgical closure of spontaneous cleft lip in CL/fraser mice].

Cleft lip with or without cleft palate is one of the most common human craniofacial congenital malformations. Failure to form a continuous tissue in the upper lip during the early embryonic period results in cleft lip. There has been an increasing interest in the possibility of in-utero correction of life threatening fetal abnormalities. In the present study, the feasibility and efficacy of surgical suturing of the fetal mouse lip was examined by using CL/Fraser mouse fetuses (spontaneous of cleft lip) at embryonic 15, 16 or 17 days. The obtained results were as follows. #1. Abortion rate of pregnant dam applied inhalation of Ethrane was less than that of intraperitoneal injection of Nembutal. #2. Successful delivery rate of fetal mouse surgically treated at the embryonic 16 day or 17 day is higher than that on the embryonic 15 day. #3. Fusion rate of mouse fetal lip surgically treated on the embryonic 16 day was higher after 60 hours in dam's uteri than that after 36 hours. These results suggest that inhalation of Ethrane is more recommendable, and that the optimal timing of fetal surgery of spontaneous cleft lip in CL/Fr. mouse fetus is an embryonic 16 day, and that the average time of 60 hours after surgical operation is enough for sutured lip to fuse in dam's uteri.

Retrospective evaluation of treatment outcome in Japanese children with complete unilateral cleft lip and palate. Part 1: Five-year-olds' index for dental arch relationships.

OBJECTIVE: To evaluate the dental arch relationships of Japanese children with complete unilateral cleft lip and palate (UCLP) and to examine the 5-year-olds' index for its validity. DESIGN: Retrospective study and comparison with previous reports. SUBJECTS: One hundred thirty-six children with complete UCLP who received primary cheiloplasty and palatoplasty in the Kyushu University Hospital from 1966 to 1999. MATERIALS: Dental models taken from children 53 to 67 months of age and their cephalograms. METHODS: Study models were assessed using five scores; 1=excellent, 2=good, 3=fair, 4=poor, and 5=very poor, in accordance with the 5-year-olds' index and also evaluated using Huddart and Bodenham's numerical classification. Dental arch widths, three-dimensional maxillary dental arch form, and lateral cephalograms were traced and measured. The outcome by 5-year-olds' index was compared with Huddart and Bodenham's numerical classification, dental arch dimensions, and cephalometric measurements. RESULTS: Occlusal outcome evaluated by the 5-year-olds' index was rated 2.95, which was classified as fair. This index rating showed a significant relationship with numerical classification and dental arch length, but not with dental arch width. The index showed a relationship with mandibular form and position, but not with maxillary position. CONCLUSION: The occlusal outcome of the cases with UCLP was fair as evaluated using the 5-year-olds' index. The index evaluates the anteroposterior relationship of maxillary/mandibular dental arches but does not evaluate the collapse of maxillary segments.

An alternative method for vermilion reconstruction after resection of hemangiomas of the lip.

PURPOSE: We describe a method for symmetrical vermilion reconstruction after resection of hemangiomas of the lip. PATIENTS AND METHODS: Four patients underwent vermilion reconstruction after resection of large cavernous hemangiomas of the lip. This reconstruction technique employed 3 basic components: 1 ) labial mucosal advancement flap, 2 ) orbicularis oris muscle flap, if necessary, and 3 ) free mucosal graft. RESULTS: All patients successfully underwent the planned procedures without significant complications. Symmetrical profiles of vermilion of the lip were achieved in all cases, even when an extended excision had been performed. CONCLUSIONS: We have found that the combination of labial mucosal advancement flaps, with or without muscular flaps, and free mucosal grafts provides excellent esthetic outcomes with a low complication rate. This method should be incorporated into the surgical techniques for symmetrical reconstruction after resection of hemangiomas of the lip.

Retrospective evaluation of craniofacial growth of Japanese children with isolated cleft palate: from palatoplasty to adolescence.

OBJECTIVES: The purposes of this study were to analyze the craniofacial growth in women with an isolated cleft palate, to compare their matured craniofacial form with that of women with normal occlusion, and to survey the factors that influenced the matured craniofacial morphology of the adults with cleft palate during their growth process. MATERIALS AND METHODS: Eighteen women with nonsyndromic isolated cleft palate were chosen from patients who received a palatoplasty at the Kyushu University Hospital, Fukuoka, Japan. Their lateral cephalometric radiographs were taken longitudinally from palatoplasty to adolescence. Fifty women with normal occlusion were chosen as controls. From their lateral cephalographs, linear and angular variables were calculated using the x,y coordinates of 20 skeletal landmarks. RESULTS: Maxillary length was shorter and the nasomaxillary complex was positioned more posteriorly in relation to the anterior cranial base of the adults with isolated cleft palate, compared with the controls. The mandible was shorter and was rotated inferiorly and posteriorly. However, remarkable deviation from the average craniofacial growth pattern was not recognized from palatoplasty to adolescence. The factors that influenced the craniofacial growth in the subjects with cleft palate were the forward growth of the A point from 2 to 5 years of age, the downward growth of the Ba point, the anterior upper facial height N-Ans in puberty, and the vertical position of the point Ba at the time of palatoplasty. CONCLUSION: This study provided evidence of the growth tendency and the factors influencing the intermaxillary relationship in subjects with isolated cleft palate. These are significant for orthodontic treatment planning.

A longitudinal study on influence of primary facial deformities on maxillofacial growth in patients with cleft lip and palate.

OBJECTIVE: The goal of this study was to use three-dimensional (3D) analysis to characterize the primary facial deformities in children with unilateral cleft lip and palate (UCLP) and then serially analyze the relationships between facial deformities and maxillofacial growth from infancy to adolescence. PARTICIPANTS: Twenty-one Japanese subjects with unilateral cleft lip and alveolus (UCLA) and 20 with UCLP who had been operated on and then followed up for more than 15 years were enrolled in this study. MAIN OUTCOME MEASURES: Facial cast models taken at cheiloplasty were scanned with a 3D laser scanner. Lateral cephalographs taken when subjects were 15 years of age or older were traced, and linear and angular measurements were calculated. The correlation between primary facial forms and maxillofacial morphology in adolescence was analyzed. RESULTS: Three-dimensional analysis showed larger ocular hypertelorism, wider cleft, greater deviation of the columella base, and more severe retruded position of the affected nasal alar base in subjects with UCLP than those with UCLA. Total surface area of the upper lips in subjects with UCLP was significantly smaller than those with UCLA. Correlation analyses revealed that the width of cleft lip, deviation of the columella base, difference of the nose base width, and surface area of the upper lip were statistically correlated with the maxillary length, the anterior position of the maxillary alveolar base, the posterior facial height, and the high angle of the mandible. CONCLUSION: The subjects who had less severe facial deformities and more tissue volume of the upper lips at cheiloplasty showed better maxillofacial growth.

Transforming growth factor-beta3 promotes mesenchymal cell proliferation and angiogenesis mediated by the enhancement of cyclin D1, Flk-1, and CD31 gene expression during CL/Fr mouse lip fusion.

BACKGROUND: Cleft lip with or without cleft palate is the most common congenital anomaly in the craniofacial region. Knowledge of the molecular mechanisms behind normal lip fusion can contribute to better intervention and improved functional clinical outcome. Transforming growth factor-beta3 (TGF-beta3) has been implicated in lip morphogenesis. Therefore, we hypothesized that TGF-beta3 functions during lip fusion through regulation of angiogenesis and mesenchymal cell cycle progression during early developmental stages. METHODS: To test this hypothesis we used the CL/Fraser mouse model, which has a high incidence of cleft lip. Lips isolated from embryonic day (ED) 11.5 mouse embryos were allowed to develop in serum-free organ cultures in the presence or absence of TGF-beta3. The lips that developed in these cultures fused in 2 days. RESULTS: During normal development, we detected positive immunoreactions for TGF-beta3 at the site of fusion. We also detected mesenchymal cells that were immunopositive for Flk-1 and CD31, which are markers for endothelial cell precursors. Exogenous TGF-beta3 accelerated lip fusion in culture. This enhancement was associated with an increase in the number of capillary blood vessels in the lips cultured in the presence of TGF-beta3, in comparison with controls. In tandem, TGF-beta3 increased the level of expression of both Flk-1 and CD31. Our data suggest that an elevated level of TGF-beta3 may promote angiogenesis in developing lips that is mediated by increased Flk-1 and CD31 expression. We also detected increased cyclin D1 expression (a marker for cell proliferation) in the presence of TGF-beta3, which suggests that TGF-beta3 promoted cell proliferation. CONCLUSIONS: TGF-beta3 promoted cell proliferation and angiogenesis in lip mesenchymal tissues. These events led to enhanced lip fusion in the presence of TGF-beta3.

TGF-beta3 induces ectopic mineralization in fetal mouse dental pulp during tooth germ development.

Several members of the transforming growth factor (TGF)-beta superfamily are expressed in developing teeth from the initiation stage through adulthood. Of those, TGF-beta1 regulates odontoblast differentiation and dentin extracellular matrix synthesis. However, the molecular mechanism of TGF-beta3 in dental pulp cells is not clearly understood. In the present study, beads soaked with human recombinant TGF-beta3 induced ectopic mineralization in dental pulp from fetal mouse tooth germ samples, which increased in a dose-dependent manner. Further, TGF-beta3 promoted mRNA expression, and increased protein levels of osteocalcin (OCN) and type I collagen (COL I) in dental pulp cells. We also observed that the expression of dentin sialophosphoprotein and dentin matrix protein 1 was induced by TGF-beta3 in primary cultured dental pulp cells, however, not in calvaria osteoblasts, whereas OCN, osteopontin and osteonectin expression was increased after treatment with TGF-beta3 in both dental pulp cells and calvaria osteoblasts. Dentin sialoprotein was also partially detected in the vicinity of TGF-beta3 soaked beads in vivo. These results indicate for the first time that TGF-beta3 induces ectopic mineralization through upregulation of OCN and COL I expression in dental pulp cells, and may regulate the differentiation of dental pulp stem cells to odontoblasts.

Relationship between primary palatal form and maxillofacial growth in Japanese children with unilateral cleft lip and palate: infancy to adolescence.

OBJECTIVE: The purpose of this retrospective study was to evaluate the relationship between the severity of maxillary defects and maxillofacial growth from infancy to adolescence in children with complete unilateral cleft lip and palate (UCLP). SUBJECTS: Thirty-one Japanese children with UCLP who had received cheiloplasty, palatoplasty, and orthodontic treatments at the Kyushu University Dental Hospital were selected. MATERIALS AND METHODS: A three-dimensional laser scanner was used to measure maxillary dental casts taken at cheiloplasty. Surface areas and volumes of the palatal tissue were calculated. Lateral cephalographs that were taken both at cheiloplasty and 15 years of age or over (average age 16.5 years) were traced and digitized. Angular and linear measurements were calculated from the x, y-coordinates. Using correlation analyses, defects in the palatal tissue were compared with maxillofacial morphology both at cheiloplasty and in adolescence or maxillofacial growth during that time span. RESULTS: (1) The surface areas or volumes of the palatal tissue were significantly correlated with the following maxillofacial measurements at infancy and adolescence: Or-depth; A-depth; PNS-height; ANS-height; N-Ba; S-N; S-Ba; N to P.P.; A'-Ptm'; Cd-Pog; Cd-Gn; Cd-G; and the N-S-Ba, S-N-A, and A-N-B angles. (2) They were also significantly correlated with the following maxillofacial growth measures from infancy to adolescence: A-depth, S-Ba, and the N-S-Ba and S-N-A angles. Only the N-S-Ba angle showed a negative correlation. CONCLUSION: The patient who had more palatal tissue at cheiloplasty showed better maxillofacial growth.