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Keiji Moriyama

Publications and source records attributed to Keiji Moriyama.

At least 19 recordsLinked to original sources
PubMed2006

Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition.

Caveolin-3, the muscle-specific isoform of caveolins, plays important roles in signal transduction. Dominant-negative mutations of the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy 1C (LGMD1C) with loss of caveolin-3. However, identification of the precise molecular mechanism leading to muscular atrophy in caveolin-3-deficient muscle has remained elusive. Myostatin, a member of the muscle-specific TGF-beta superfamily, negatively regulates skeletal muscle volume. Here we report that caveolin-3 inhibited myostatin signaling by suppressing activation of its type I receptor; this was followed by hypophosphorylation of an intracellular effector, Mad homolog 2 (Smad2), and decreased downstream transcriptional activity. Loss of caveolin-3 in P104L mutant caveolin-3 transgenic mice caused muscular atrophy with increase in phosphorylated Smad2 (p-Smad2) as well as p21 (also known as Cdkn1a), a myostatin target gene. Introduction of the myostatin prodomain, an inhibitor of myostatin, by genetic crossing or intraperitoneal administration of the soluble type II myostatin receptor, another inhibitor, ameliorated muscular atrophy of the mutant caveolin-3 transgenic mice with suppression of p-Smad2 and p21 levels. These findings suggest that caveolin-3 normally suppresses the myostatin-mediated signal, thereby preventing muscular atrophy, and that hyperactivation of myostatin signaling participates in the pathogenesis of muscular atrophy in a mouse model of LGMD1C. Myostatin inhibition may be a promising therapy for LGMD1C patients.

Animals↗
PubMed2006

Function and regulation of osteopontin in response to mechanical stress.

UNLABELLED: Extensive histological study revealed the impairment of bone remodeling caused by mechanical stress in OPN knockout mice in a tooth movement system. Analysis of OPN promoter transgenic mice showed the mechanical stress response element(s) in the 5.5-kb upstream region. These results were also obtained with the primary cultured cells. INTRODUCTION: Mechanical loading system changes the bone architecture through the stimulation of bone remodeling by the action of a numbers of molecules. Among them, we showed that osteopontin (OPN) plays an important role in response to mechanical loading in rats with an experimental system for tooth movement. The results indicate the important role of OPN in bone remodeling. However, the molecular mechanism of OPN expression in response to mechanical stress is unknown. MATERIALS AND METHODS: OPN knockout mice and transgenic mice carrying green fluorescent protein (GFP) in the control of the OPN promoter were used for analysis. Orthodontic closed coil springs were bonded to the maxillary first molars and incisors for the experimental tooth movement. Spatial expression of GFP and OPN was detected by in situ hybridization. RESULTS: In contrast to wildtype mice, a smaller number of TRACP+ cells was detected in OPN knockout mice after treatment. In GFP-OPN5.5 mice, OPN and GFP mRNA-expressing cells were detected in bone cells after treatment, and the localization of GFP was consistent with that of endogenous OPN. An increase in the co-expression of GFP and OPN was detected when primary cultured osteoblastic cells derived from the transgenic mice were exposed to strain or pressure force. Significant increase in the number of OPN+ osteocyte was detected in the pressure side at 48 h after treatment. At 72 h, increase in the number of TRACP+ cells was detected predominantly in the pressure side. CONCLUSIONS: Bone remodeling in response to mechanical stress was suppressed in OPN knockout mice. These results indicate the critical role of OPN in the process of bone remodeling. The analysis of GFP expression in the promoter transgenic mice indicated the presence of an in vivo mechanical stress response element in the 5.5-kb upstream region of the OPN gene.

Animals↗
PubMed2005

Malignant B-lymphoid cells with bone lesions express receptor activator of nuclear factor-kappaB ligand and vascular endothelial growth factor to enhance osteoclastogenesis.

PURPOSE: Receptor activator of nuclear factor-kappaB ligand (RANKL) is a key mediator of osteoclastogenesis. Because certain types of tumor cells aberrantly express RANKL, and because bone destruction also develops in B-cell lymphomas of bone origin, we investigated RANKL expression and the mechanisms of osteoclastogenesis in B-lymphoid neoplasms. EXPERIMENTAL DESIGN AND RESULTS: Immunohistochemistry of bone specimens resected from patients with primary B-cell lymphoma of bone with bone destruction revealed that lymphoma cells express RANKL as well as vascular endothelial cell growth factor (VEGF). The tumor cells isolated from the bone specimens enhanced osteoclastogenesis in vitro. In contrast, B-cell lymphoma infiltrating to the bone marrow without bone destruction did not express RANKL. Both RANKL and VEGF were expressed by a portion of B-lymphoid cell lines, including Daudi and IM-9. These RANKL-expressing tumor cells enhanced osteoclastogenesis from RAW264.7 cells and human monocyte-derived preosteoclasts in the absence of stromal cells/osteoblasts in a RANKL-dependent manner. Furthermore, conditioned media from Daudi cells enhanced transmigration of preosteoclasts that was inhibited by anti-VEGF antibody, suggesting that tumor cell-derived VEGF mediates recruitment of osteoclast precursors. Moreover, cocultures of B-lymphoid cell lines with osteoclasts enhanced the growth of B-lymphoid cells. CONCLUSIONS: Some malignant B cells aberrantly express functional RANKL as well as VEGF to enhance osteoclastogenesis. The coexpression of RANKL and VEGF may also contribute to the close cellular interactions with osteoclastic cells, thereby forming a vicious cycle between osteoclastic bone destruction and tumor expansion in bone.

Bone Neoplasms↗
PubMed2005

Messenger RNA expression of periostin and Twist transiently decrease by occlusal hypofunction in mouse periodontal ligament.

Periostin, which is a secreted protein that supports cell adhesion, is highly expressed in the periodontal ligament (PDL). Twist, a basic helix-loop-helix (bHLH) transcription factor and a negative regulator of osteoblast differentiation, has been found to regulate the periostin gene transcription. Since occlusal force is thought to be important in the homeostasis of the PDL, in this study we investigated the expression of periostin and Twist mRNA in the mouse periodontal tissue following removal of antagonizing teeth. Unilateral maxillary tooth extraction was performed in 3-week-old male mice to produce occlusal hypofunction of the right mandibular molars. The expressions of periostin and Twist mRNA were examined by real time-PCR and in situ hybridization at 12, 24, 72 and 168 h after the tooth extraction. The real-time PCR analysis showed that periostin and Twist mRNA significantly decreased at 24 h to 14.5 and 49.9% of those in control group, respectively. But the recovery began at 72 and 168 h, no significant difference was observed. As determined by in situ hybridization analysis, the number of periostin and Twist mRNA-expressing PDL cells showed a marked decrease at 24 h, although an increase was observed from 72 h until the distribution was almost similar to that of the control group at 168 h. These results suggested that occlusal force might have putative roles in periostin and Twist gene expression in the PDL and the changes in their expression level during hypofunction may be considered a form of adaptation to environmental changes.

Animals↗
PubMed2005

Identification of cis-element regulating expression of the mouse Fgf10 gene during inner ear development.

Fibroblast growth factor (FGF) signaling is crucial for the induction and growth of the ear, a sensory organ that involves intimate tissue interactions. Here, we report the abnormality of Fgf10 null ear and the identification of a cis-regulatory element directing otic expression of Fgf10. In Fgf10 null inner ears, we found that the initial development of semicircular, vestibular, and cochlear divisions is roughly normal, after which there are abnormalities of semicircular canal/cristae and vestibular development. The mutant semicircular disks remain without canal formation by the perinatal stage. To elucidate regulation of the Fgf10 expression during inner ear development, we isolated a 6.6-kb fragment of its 5'-upstream region and examined its transcriptional activity with transgenic mice, using a lacZ-reporter system. From comparison of the mouse sequences of the 6.6-kb fragment with corresponding sequences of the human and chicken Fgf10, we identified a 0.4-kb enhancer sequence that drives Fgf10 expression in the developing inner ear. The enhancer sequences have motifs for many homeodomain-containing proteins (e.g., Prx, Hox, Nkx), in addition to POU-domain factors (e.g., Brn3), zinc-finger transcription factors (e.g., GATA-binding factors), TCF/LEF-1, and a SMAD-interacting protein. Thus, FGF10 signaling is dispensable for specification of otic compartment identity but is required for hollowing the semicircular disk. Furthermore, the analysis of a putative inner ear enhancer of Fgf10 has disclosed a complicated regulation of Fgf10 during inner ear development by numerous transcription factors and signaling pathways.

Animals↗
PubMed2005

Siblings with spaced arches treated with and without partial glossectomy.

Macroglossia, or enlarged tongue, is thought to be an etiological factor in open bite, bimaxillary protrusion, and dental arch spacing, and it might cause instability after orthodontic treatment. Partial glossectomy to reduce tongue size might be a useful method of solving these problems. In this report, we describe orthodontic treatment of 2 siblings with enlarged tongues and arch-space problems. The sister, whose tongue was larger and spacing problem more severe, was treated with a partial glossectomy; her brother refused surgery and was treated with a tongue-crib appliance. Stability after orthodontic treatment was evaluated.

Adolescent↗
PubMed2005

Orthodontic treatment of a traumatically intruded tooth with ankylosis by traction after surgical luxation.

This report presents the treatment of a patient with anterior crossbite and displacement of ankylosed maxillary and mandibular right lateral incisors. The maxillary lateral incisor, which was traumatically intruded, was successfully treated with 2 surgical luxations followed by orthodontic traction. The mandibular lateral incisor, which was avulsed and replanted, experienced replacement root resorption during orthodontic treatment and was ultimately extracted. Two years after active orthodontic treatment, the occlusal results were considered satisfactory.

Cephalometry↗
PubMed2005

Hydrogen embrittlement of work-hardened Ni-Ti alloy in fluoride solutions.

Hydrogen embrittlement of work-hardened Ni-Ti alloy has been examined in acidulated phosphate fluoride (APF) solutions. Upon immersion in a 2.0% APF solution with a pH of 5.0, tensile strength decreased markedly with immersion time. Moreover, the fracture mode changed from ductile to brittle due to brittle layer formation at the peripheral part of the cross section of the specimen. The amount of absorbed hydrogen increased linearly with immersion time, and it reached above 5000 mass ppm after 24 h. The hydrogen desorption temperature of the immersed specimens shifted from 450 degrees C to a lower temperature with immersion time. As the amount of absorbed hydrogen was larger than 500 mass ppm, the degradation of mechanical properties was recognized. Although the tensile properties and fracture mode scarcely change in a 0.2% APF solution, the slight reduction in hardness and hydrogen absorption of several hundreds mass ppm were observed. The results of the present study imply that work-hardened Ni-Ti alloy is less sensitive to hydrogen embrittlement compared with Ni-Ti superelastic alloy.

Absorption↗
PubMed2005

An interdisciplinary approach for improved functional and esthetic results in a periodontally compromised adult patient.

In contemporary dental care, an increasing number of adult patients are seeking orthodontic treatment. In such adult patients, a combined orthodontic and other specialized therapy often offers the best option for achieving a predictable outcome to solve complex clinical problems. This case report demonstrates a combined therapy with orthodontic, periodontic, and implant-prosthodontic treatments in a 56-year six-month-old female patient with mild diastemata in the maxillary anterior region and a missing left maxillary second premolar caused by a periodontal disease with medium bone loss. The patient had improved her oral hygiene condition through periodontal treatment before orthodontic treatment. The patient was orthodontically treated with a maxillary lingual arch and a maxillary edgewise orthodontic appliance. Active orthodontic treatment was completed in 18 months, and an implant-supported prosthesis was placed with a single crown in the region of the left maxillary second premolar. The treatment outcomes, including the periodontal condition and the dental implant treatment, were stable at two years after the active orthodontic treatment. We demonstrate that combined orthodontic-periodontic-implant-prosthodontic treatment can achieve an improved masticatory function, esthetics, occlusion, and periodontal condition.

Alveolar Bone Loss↗
PubMed2004

A soluble form of fibroblast growth factor receptor 2 (FGFR2) with S252W mutation acts as an efficient inhibitor for the enhanced osteoblastic differentiation caused by FGFR2 activation in Apert syndrome.

Apert syndrome is an autosomal dominant disease characterized by craniosynostosis and bony syndactyly associated with point mutations (S252W and P253R) in the fibroblast growth factor receptor (FGFR) 2 that cause FGFR2 activation. Here we investigated the role of the S252W mutation of FGFR2 on osteoblastic differentiation. Osteoblastic cells derived from digital bone in two Apert patients with the S252W mutation showed more prominent alkaline phosphatase activity, osteocalcin and osteopontin mRNA expression, and mineralized nodule formation compared with the control osteoblastic cells derived from two independent non-syndromic polydactyly patients. Stable clones of the human MG63 osteosarcoma cells (MG63-Ap and MG63-IIIc) overexpressing a splice variant form of FGFR2 with or without the S252W mutation (FGFR2IIIcS252W and FGFR2IIIc) showed a higher RUNX2 mRNA expression than parental MG63 cells. Furthermore MG63-Ap exhibited a higher osteopontin mRNA expression than did MG63-IIIc. The enhanced osteoblastic marker gene expression and mineralized nodule formation of the MG63-Ap was inhibited by the conditioned medium from the COS-1 cells overexpressing the soluble FGFR2IIIcS252W. Furthermore the FGF2-induced osteogenic response in the mouse calvarial organ culture system was blocked by the soluble FGFR2IIIcS252W. These results show that the S252W mutation in the FGFR2 gene enhances the osteoblast phenotype in human osteoblasts and that a soluble FGFR2 with the S252W mutation controls osteoblast differentiation induced by the S252W mutation through a dominant negative effect on FGFR2 signaling in Apert syndrome.

Acrocephalosyndactylia↗
PubMed2004

Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion.

Multiple myeloma (MM) expands in the bone marrow and causes devastating bone destruction by enhancing osteoclastic bone resorption in its vicinity, suggesting a close interaction between MM cells and osteoclasts (OCs). Here, we show that peripheral blood mononuclear cell-derived OCs enhanced growth and survival of primary MM cells as well as MM cell lines more potently than stromal cells, and that OCs protected MM cells from apoptosis induced by serum depletion or doxorubicin. OCs produced osteopontin (OPN) and interleukin 6 (IL-6), and adhesion of MM cells to OCs increased IL-6 production from OCs. In addition, IL-6 and OPN in combination enhanced MM cell growth and survival. However, the effects of OCs on MM cell growth and survival were only partially suppressed by a simultaneous addition of anti-IL-6 and anti-OPN antibodies and were completely abrogated by inhibition of cellular contact between MM cells and OCs. These results demonstrate that OCs enhance MM cell growth and survival through a cell-cell contact-mediated mechanism that is partially dependent on IL-6 and OPN. It is suggested that interactions of MM cells with OCs augment MM growth and survival and, thereby, form a vicious cycle, leading to extensive bone destruction and MM cell expansion.

Animals↗
PubMed2004

Delayed fracture of Ni-Ti superelastic alloys in acidic and neutral fluoride solutions.

Hydrogen-related degradation of the mechanical properties of a Ni-Ti superelastic alloy has been examined by means of delayed fracture tests in acidic and neutral fluoride solutions and hydrogen thermal desorption analysis. Delayed fracture took place in both solutions; the time to fracture was shorter in the acidic solutions than in the neutral solutions with the same fluoride concentration. The time to fracture was reduced in both solutions when applied stress exceeded the critical stress for martensite transformation. In the acidic solutions, Ni-Ti superelastic alloy underwent general corrosion and absorbed substantial amounts of hydrogen. Fractographic features suggested that the delayed fracture in the acidic solutions was attributable to hydrogen embrittlement, whereas in the neutral solutions, a different fracture mode appeared associated with localized corrosion only in the vicinity of the fracture initiation area. In the neutral solutions, the amount of absorbed hydrogen was much less than that in the acidic solutions, and the delayed fracture was likely to be induced by active path corrosion accompanying hydrogen absorption. The results of the present study imply that the hydrogen-related degradation of performance of Ni-Ti superelastic alloys occurs in the presence of fluoride.

Corrosion↗
PubMed2004

Estrogen deficiency accelerates murine autoimmune arthritis associated with receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenesis.

The aims of this study were to evaluate the in vivo effects of estrogen deficiency in MRL/lpr mice as a model for rheumatoid arthritis and to analyze the possible relationship between immune dysregulation and receptor activator of nuclear factor-kappaB ligand (RANKL)-mediated osteoclastogenesis. Experimental studies were performed in ovariectomized (Ovx)-MRL/lpr, Ovx-MRL+/+, sham-operated-MRL/lpr, and sham-operated-MRL+/+ mice. Severe autoimmune arthritis developed in younger Ovx-MRL/lpr mice until 24 wk of age, whereas these lesions were entirely recovered by pharmacological levels of estrogen administration. A significant elevation in serum rheumatoid factor, anti-double-stranded DNA, and anti-type II collagen was found in Ovx-MRL/lpr mice and recovered in mice that underwent estrogen administration. A high proportion of CD4(+) T cells bearing RANKL was found, and an enhanced expression of RANKL mRNA and an impaired osteoprotegerin mRNA was detected in the synovium. An increase in both osteoclast formation and bone resorption pits was found. These results indicate that estrogen deficiency may play a crucial role in acceleration of autoimmune arthritis associated with RANKL-mediated osteoclastogenesis in a murine model for rheumatoid arthritis.

Animals↗
PubMed2004

Degradation in performance of orthodontic wires caused by hydrogen absorption during short-term immersion in 2.0% acidulated phosphate fluoride solution.

The purpose of this study was to investigate the degradation in performance of four major alloys of orthodontic wires, namely nickel-titanium, beta titanium, stainless steel, and cobalt-chromium-nickel, caused by hydrogen absorption during short-term immersion in an acid fluoride solutions. The hydrogen-related degradation of orthodontic wires after immersion in 2.0% acidulated phosphate fluoride solution at 37 degrees C for 60 minutes was evaluated by a tensile test, scanning electron microscope observation, and hydrogen thermal desorption analysis. Upon immersion, the tensile strengths of the nickel-titanium and beta titanium wires decreased. Particularly, the nickel-titanium wire fractured before yielding, and the fracture mode changed from ductile to brittle. The amounts of absorbed hydrogen in the nickel-titanium and beta titanium wires were 200 and 100 mass ppm, respectively. On the other hand, the tensile strengths of the stainless steel and cobalt-chromium-nickel wires were only slightly affected by immersion. The results of this study suggest that degradation in performance of orthodontic wires of titanium alloys occurs because of hydrogen absorption even after a short-term immersion in fluoride solutions.

Acidulated Phosphate Fluoride↗
PubMed2004

Occlusal difficulties after simultaneous mandibular and maxillary distraction in an adult case of hemifacial microsomia.

A 23-year-old woman with hemifacial microsomia type IIB was treated by simultaneous mandibular and maxillary distraction. During the course of the distraction, cephalometric analysis showed that the maxilla was not moving downward and that the upper edge of the mandibular condyle was moving upward into the space between the condyle and the glenoid fossa. This phenomenon could lead to early consolidation of the osteotomized maxilla, resulting in malposition and occlusal difficulties. This is thought to be a problem unique to bimaxillary distraction of hemifacial microsomia type IIB with severe hypoplasia of the mandibular ramus and space between the condyle and the glenoid fossa. Surgeons should be alerted to this risk and prepared to address it when performing this procedure.

Adult↗
PubMed2004

Identification of promoter regions involved in cell- and developmental stage-specific osteopontin expression in bone, kidney, placenta, and mammary gland: an analysis of transgenic mice.

UNLABELLED: Cell-specific expression of GFP under the control of different lengths of the osteopontin promoter in transgenic mice identified the positive and negative regulatory regions for respective cell types. The results provide new insights for physiological and pathological expression of the osteopontin gene. INTRODUCTION: Osteopontin (OPN) is a major non-collagenous bone matrix protein that is involved in normal and pathological calcification and is expressed in a tissue-specific manner. To investigate how such tissue-specific OPN gene expression is regulated in vivo, transgenic mice expressing the green fluorescent protein (GFP) reporter gene controlled by different lengths of the OPN promoter were generated. MATERIALS AND METHODS: Cell- and developmental stage-specific osteopontin expression in transgenic mice was examined by Northern blotting, immunoblotting, fluorescence examination, and in situ hybridization and compared with those of OPN. RESULTS AND CONCLUSIONS: The line bearing the -5505 to +14 region of the OPN promoter was shown by Northern blotting and immunoblotting to express GFP in the same cells that express endogenous OPN (osteoblasts, hypertrophic chondrocytes, renal and mammary gland epithelial cells, and granulated metrial gland [GMG] placental cells) at the same stage in development. Thus, the 5.5-kb -5505 to +14 promoter region is sufficient for proper tissue-specific OPN expression. The lines carrying shorter segments of the OPN promoter showed different expression patterns. These patterns revealed a putative cis-acting element in the -5269 to -5263 region that restricts OPN expression to hypertrophic chondrocytes and a mammary gland-specific expressing element and a GMG cell-specific enhancing element in the -5505 to -3156 region. Furthermore, the -3155 to -1576 region seems to contain positive renal epithelial cell- and GMG cell-specific expression motif(s) as well as a negative regulatory element that prevents OPN expression in fibroblasts. Moreover, the -1576 to -910 region seems to contain a positive osteoblast-specific-expressing element. Thus, the 5.5-kb OPN promoter contains multiple cis-acting elements encoding positive and negative cell-specific regulatory systems.

Animals↗
PubMed2004

Oral rehabilitation of an orthodontic patient with cleft lip and palate and hypodontia using secondary bone grafting, osseo-integrated implants, and prosthetic treatment.

OBJECTIVE: Complete skeletal and dental reconstruction of the anterior maxilla is of great importance to patients with cleft lip and palate. Accordingly, osseo-integrated implants have been utilized for dental reconstruction after secondary bone grafting. In this report, the orthodontic management of a patient with unilateral cleft lip and plate with associated hypodontia is described. The patient was treated with comprehensive orthodontic treatment in addition to secondary bone grafting, and dental reconstruction was achieved with a combination of osseo-integrated implants and fixed prosthodontic treatment.

Alveoloplasty↗