38 results on '"Katsuhiko Amano"'
Search Results
2. A sporadic case of Gigantiform Cementoma with mild and atypical clinical manifestation
- Author
-
Shun Kasahara, Katsuhiko Amano, Kyoko Kurioka, Masato Minohara, Mikihiko Kogo, and Susumu Tanaka
- Subjects
Otorhinolaryngology ,Surgery ,Oral Surgery ,Pathology and Forensic Medicine - Published
- 2023
3. The secondary case of melanotic neuroectodermal tumor in the infant maxilla: Long-term observation after the enucleation
- Author
-
Kyoko Kurioka, Katsuhiko Amano, Kazuma Harada, Masaya Okura, Mikihiko Kogo, and Susumu Tanaka
- Subjects
Otorhinolaryngology ,Surgery ,Oral Surgery ,Pathology and Forensic Medicine - Published
- 2022
4. Effects of mechanical stress and deficiency of dihydrotestosterone or 17β-estradiol on Temporomandibular Joint Osteoarthritis in mice
- Author
-
Katsuhiko Amano, Kenji Sueishi, Masashi Nagao, Yoichi Ishizuka, Akira Watanabe, Takenobu Ishii, Tomohisa Ootake, Yasushi Nishii, and Kazuaki Nishimura
- Subjects
Male ,medicine.medical_specialty ,Carbonic Anhydrase I ,Ovariectomy ,Biomedical Engineering ,Osteoclasts ,Osteoarthritis ,Chondrocyte ,Condyle ,Chondrocytes ,stomatognathic system ,Rheumatology ,Internal medicine ,medicine ,Animals ,Orthopedics and Sports Medicine ,Orchiectomy ,Angiopoietin-Like Protein 7 ,Estradiol ,Temporomandibular Joint ,business.industry ,Mandibular Condyle ,Calcinosis ,Dihydrotestosterone ,medicine.disease ,Up-Regulation ,Temporomandibular joint ,Mice, Inbred C57BL ,Disease Models, Animal ,stomatognathic diseases ,medicine.anatomical_structure ,Endocrinology ,Female ,Stress, Mechanical ,business ,medicine.drug ,Calcification ,Hormone - Abstract
Summary Objective To observe and analyze the interaction between excessive mechanical stress (MS) and decreased sex hormones on Temporomandibular Joint Osteoarthritis (TMJ-OA), and to discover TMJ-OA disease susceptibility genes by molecular biological analysis to elucidate part of the mechanism of TMJ-OA onset. Design For experimental groups, orchiectomy (ORX) or ovariectomy (OVX) was performed on sexually mature 8-week-old mice. A metal plate was attached to the posterior surface of the maxillary incisors to apply excessive MS on mandibular condyles. Male mice were divided into control, ORX, MS, and ORX + MS groups, while female mice were divided into control, OVX, MS, and OVX + MS groups. Mandibular condyles were evaluated by histology and molecular biology. Results Histomorphometric analysis of the TMJ in ORX + MS and OVX + MS groups revealed the thinnest chondrocyte layers, highest modified Mankin scores, and significant increases in the number of osteoclasts. Gene expression analysis indicated upregulation of Angptl7 and Car1 genes in the mandibular condyles of mice subjected to the combined effects of excessive MS and reduced sex hormones. In vitro analysis suggested that cartilage-like cells overexpressing Angptl7 enhanced calcification, and osteoblast-like cells overexpression Car1 suppressed cell proliferation and calcification. Conclusions A severe TMJ-OA mouse model was successfully developed by applying excessive MS on the mandibular condyle of male and female mice with reduced sex hormones. Disease-susceptibility genes Angptl7 and Car1 were newly discovered in the experimental groups, suggesting their involvement in the onset mechanism of TMJ-OA.
- Published
- 2021
5. Indian hedgehog in craniofacial neural crest cells links to skeletal malocclusion by regulating associated cartilage formation and gene expression
- Author
-
Katsuhiko Amano, Tomonao Aikawa, Daisuke Okuzaki, and Mikihiko Kogo
- Subjects
Male ,0301 basic medicine ,Indian hedgehog ,Mice, Transgenic ,Wnt1 Protein ,Biochemistry ,Bone and Bones ,Craniofacial Abnormalities ,Mice ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Genetics ,medicine ,Nasal septum ,Animals ,Hedgehog Proteins ,Craniofacial ,Nasal cartilages ,Molecular Biology ,Endochondral ossification ,Mice, Knockout ,biology ,Cartilage ,Gene Expression Regulation, Developmental ,Neural crest ,Anatomy ,biology.organism_classification ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,Neural Crest ,Female ,Chondrogenesis ,Nasal concha ,Malocclusion ,030217 neurology & neurosurgery ,Biotechnology - Abstract
The frontal craniofacial skeleton derived from neural crest cells is vital for facial structure and masticatory functions. The exact role of Indian hedgehog (Ihh) in facial and masticatory development has not been fully explored. In this study, we generated craniofacial neural crest cells-specific Ihh deletion mice (Wnt1-Cre;Ihhfl/fl ;Tomatofl/+ ) and found the gradual dwarfism without perinatal lethality. Morphological and histological analyses revealed unambiguous craniofacial phenotypes in mutants, where we observed skeletal malocclusion accompanied by markedly hypoplastic nasomaxillary complex and reversed incisor occlusion. Both the replacement of nasal concha cartilage by turbinate bones and the endochondral ossification of nasal septum ethmoid bone were substantially delayed. We also observed hypoplastic mandibles in mutants where the mandibular ramus was unexpectedly the most affected. Both the condylar process and mandibular angle cartilages were distorted. However, dental examination showed no significant changes in teeth and dentition. Finally, a comprehensive RNA sequence analysis utilizing condylar cartilage identified Ihh-associated gene network including several cell cycle genes and 16 genes related to the extracellular matrix, sulfate transporters, transcription factors, receptors, a ciliogenesis factor, and an adhesion molecule. Our data provide direct in vivo evidence that Ihh plays crucial roles in midface and masticatory system formation, likely by activating key genes.
- Published
- 2020
6. A case of modified Furlow palatoplasty applied to a Campomelic dysplasia patient
- Author
-
Makoto Fujiwara, Katsuhiko Amano, Koichi Otsuki, Mikihiko Kogo, and Kyoko Kurioka
- Subjects
medicine.medical_specialty ,Soft palate ,Respiratory distress ,business.industry ,030206 dentistry ,Perioperative ,SOX9 ,medicine.disease ,Congenital skeletal disorder ,Pathology and Forensic Medicine ,Surgery ,Campomelic dysplasia ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Otorhinolaryngology ,Furlow palatoplasty ,030220 oncology & carcinogenesis ,medicine ,Oral Surgery ,Craniofacial ,business - Abstract
Campomelic dysplasia (CMPD) is a rare congenital skeletal disorder caused by SOX9 mutations. The patients are often accompanied by craniofacial and oral anomalies such as characteristic facial appearance and cleft palate. In spite of possibility of perinatal lethality, some patients could survive with milder phenotype and appropriate medical treatment. Such patients might cause critical issues in feeding and require oral management. However, there has been less information about oral surgical treatment in CMPD patients. Here, we describe our recent experience of diagnosis and cleft palate repair in a CMPD patient. A 27 month old Japanese female presenting typical CMPD phenotypes was genetically determined and a SOX9Q175Stop mutation was identified. The protein analysis demonstrated that SOX9Q175Stop mutation yields the truncated protein lacking the transactivation site. The affected infant had serious respiratory distress and always required control by an artificial ventilator. Cleft palate reconstruction under general anesthesia was performed to improve her feeding and oral functions. Modified Furlow palatoplasty was applied to minimize surgical invasion in which only a unilateral relaxation incision was designed. Artificial skin material was used to support fragile soft palate tissue. Although there was some risk to cause any serious respiratory issue, her SpO2 was maintained well through the perioperative period. Our case report might provide valuable information for syndromic cleft palate treatments.
- Published
- 2019
7. Klotho expression in osteocytes regulates bone metabolism and controls bone formation
- Author
-
Kenichi Nagano, Roland Baron, Hannes Olauson, Hirotaka Komaba, Katsuhiko Amano, Tadatoshi Sato, Jovana Kaludjerovic, Tobias E. Larsson, Dorothy Hu, Michael J. Densmore, Noriko Ide, Jun-ichi Hanai, Teresita Bellido, and Beate Lanske
- Subjects
0301 basic medicine ,Aging ,medicine.medical_specialty ,Primary Cell Culture ,Down-Regulation ,Osteoclasts ,urologic and male genital diseases ,Osteocytes ,Bone and Bones ,Bone remodeling ,Mice ,03 medical and health sciences ,Downregulation and upregulation ,Bone Density ,Osteogenesis ,Osteoclast ,Internal medicine ,Bone cell ,medicine ,Animals ,Humans ,Renal osteodystrophy ,Klotho Proteins ,Klotho ,Glucuronidase ,Chronic Kidney Disease-Mineral and Bone Disorder ,Mice, Knockout ,Osteoblasts ,Chemistry ,Cell Differentiation ,Osteoblast ,medicine.disease ,Immunohistochemistry ,female genital diseases and pregnancy complications ,Cell biology ,Fibroblast Growth Factors ,Disease Models, Animal ,Fibroblast Growth Factor-23 ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Nephrology ,Osteocyte ,Female ,Signal Transduction - Abstract
Osteocytes within the mineralized bone matrix control bone remodeling by regulating osteoblast and osteoclast activity. Osteocytes express the aging suppressor Klotho, but the functional role of this protein in skeletal homeostasis is unknown. Here we identify Klotho expression in osteocytes as a potent regulator of bone formation and bone mass. Targeted deletion of Klotho from osteocytes led to a striking increase in bone formation and bone volume coupled with enhanced osteoblast activity, in sharp contrast to what is observed in Klotho hypomorphic (kl/kl) mice. Conversely, overexpression of Klotho in cultured osteoblastic cells inhibited mineralization and osteogenic activity during osteocyte differentiation. Further, the induction of chronic kidney disease with high-turnover renal osteodystrophy led to downregulation of Klotho in bone cells. This appeared to offset the skeletal impact of osteocyte-targeted Klotho deletion. Thus, our findings establish a key role of osteocyte-expressed Klotho in regulating bone metabolism and indicate a new mechanism by which osteocytes control bone formation.
- Published
- 2017
8. Ihh and PTH1R signaling in limb mesenchyme is required for proper segmentation and subsequent formation and growth of digit bones
- Author
-
Katsuhiko Amano, Yi Fan, Michael J. Densmore, and Beate Lanske
- Subjects
0301 basic medicine ,Mesoderm ,Histology ,Indian hedgehog ,Physiology ,Endocrinology, Diabetes and Metabolism ,Mesenchyme ,Cre recombinase ,medicine.disease_cause ,Bone and Bones ,Chondrocyte ,Mice ,03 medical and health sciences ,Chondrocytes ,0302 clinical medicine ,Osteogenesis ,medicine ,Animals ,Hedgehog Proteins ,Endochondral ossification ,In Situ Hybridization ,Body Patterning ,Receptor, Parathyroid Hormone, Type 1 ,Mutation ,Integrases ,biology ,Cartilage ,Extremities ,Anatomy ,Toes ,biology.organism_classification ,Cell biology ,body regions ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,Synostosis ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Digit formation is a process, which requires the proper segmentation, formation and growth of phalangeal bones and is precisely regulated by several important factors. One such factor is Ihh, a gene linked to BDA1 and distal symphalangism in humans. In existing mouse models, mutations in Ihh have been shown to cause multiple synostosis in the digits but lead to perinatal lethality. To better study the exact biological and pathological events which occur in these fused digits, we used a more viable Prx1-Cre;Ihh(fl/fl) model in which Cre recombinase is expressed during mesenchymal condensation in the earliest limb buds at E9.5 dpc and found that mutant digits continuously fuse postnatally until phalanges are finally replaced by an unsegmented "one-stick bone". Mutant mice displayed osteocalcin-positive mature osteoblasts, but had reduced proliferation and abnormal osteogenesis. Because of the close interaction between Ihh and PTHrP during endochondral ossification, we also examined the digits of Prx1-Cre;PTH1R(fl/fl) mice, where the receptor for PTHrP was conditionally deleted. Surprisingly, we found PTH1R deletion caused symphalangism, demonstrating another novel function of PTH1R signaling in digit formation. We characterized the symphalangism process whereby initial cartilaginous fusion prevented epiphyseal growth plate formation, resulting in resorption and replacement of the remaining cartilage by bony tissue. Chondrocyte differentiation displayed abnormal directionality in both mutants. Lastly, Prx1-Cre;Ihh(fl/fl);Jansen Tg mice, in which a constitutively active PTH1R allele was introduced into Ihh mutants, were established to address the possible involvement of PTH1R signaling in Ihh mutant digits. These rescue mice failed to show significantly improved phenotype, suggesting that PTH1R signaling in chondrocytes is not sufficient to restore digit formation. Our results demonstrate that Ihh and PTH1R signaling in limb mesenchyme are both essential to regulate proper development of digit structures, although they appear to use different mechanisms.
- Published
- 2016
9. Regulation of transcriptional network system during bone and cartilage development
- Author
-
Katsuhiko Amano, K. Ono, Toshiyuki Yoneda, Yoko Takigawa, Kenji Hata, Rikako Takashima, Fumiyo Ikeda, Riko Nishimura, Eriko Nakamura, Michiko Yoshida, and Takuma Matsubara
- Subjects
Cartilage ,Medicine (miscellaneous) ,Osteoblast ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Chondrocyte ,Cell biology ,Haematopoiesis ,medicine.anatomical_structure ,Osteoclast ,Immunology ,medicine ,General Dentistry ,Transcription factor ,Function (biology) ,Hormone - Abstract
Background Bone and cartilage are essential skeletal tissues, which not only function as structural basis of locomotive organs, but also regulate calcium homeostasis, phosphate metabolism, hematopoiesis, and glucose turnover. Several hormones and cytokines in cooperation with their downstream transcription factors regulate bone and cartilage development; therefore, it is important to understand the precise mechanisms of this regulation. Highlight Genetic studies in human and mouse have provided a wealth of information regarding the transcription factors implicated in bone and cartilage development. Moreover, innovative molecular cloning techniques identified several new transcription factors that play indispensable roles in controlling the development of bone and cartilage. The mechanisms controlling the expression of these transcription factors have been meticulously elucidated, so that the transcriptional network system, which seemed so complex and mysterious not so long ago, has become considerably clearer in recent years. Conclusion Recent advances in our knowledge about transcriptional network systems contributed to understanding the molecular underpinnings of regulation and pathological disease mechanisms in bone and cartilage.
- Published
- 2015
10. Conditional Deletion of Indian Hedgehog in Limb Mesenchyme Results in Complete Loss of Growth Plate Formation but Allows Mature Osteoblast Differentiation
- Author
-
Beate Lanske, Katsuhiko Amano, and Michael J. Densmore
- Subjects
medicine.medical_specialty ,Indian hedgehog ,biology ,Endocrinology, Diabetes and Metabolism ,Mesenchyme ,Mesenchymal cell differentiation ,Osteoblast ,biology.organism_classification ,Prenatal development ,Bone remodeling ,body regions ,Endocrinology ,medicine.anatomical_structure ,Osteoclast ,Internal medicine ,medicine ,Osteocalcin ,biology.protein ,Orthopedics and Sports Medicine - Abstract
Indian hedgehog (Ihh) is widely recognized as an essential factor for proper skeletal development. Previous in vivo studies using mutant Ihh mouse models were limited by perinatal lethality or carried out after a growth plate formed. Thus the important role of Ihh in mesenchymal cell differentiation has not been investigated. In this study, we established Prx1-Cre;Ihh(fl/fl) mice to ablate Ihh specifically in limb mesenchyme to allow us to observe the phenotype continuously from prenatal development to 3 weeks of age. Mutant mice displayed severe limb abnormalities characterized by complete lack of secondary ossification center and growth plate, indicating an essential role for Ihh in the development of these structures. Interestingly, we discovered that osteoblast differentiation and bone formation could occur in conditions of deficient Ihh. This is a novel finding that has not been observed because of the early lethality of previous Ihh mutants. Mature osteoblasts expressing osteocalcin could be detected in the center of mutant bones at postnatal day 10 (P10). Osteoclasts and blood vessel formation were also present, suggesting active bone remodeling. Histomorphometric analyses show a significant increase in osteoclast number with no major changes in bone formation rate at 3 weeks of age. Mutant long bones in the limbs were deformed, with cortices comprised of irregular woven bone. Also, there was a marked decrease in gene expression of osteoblastic and osteocytic markers. Moreover, mutant long bones displayed bone dysplasia in which we observed increased osteoclast activity and partially reduced osteoblastic and osteocytic differentiation that lead ultimately to loss of bone structures at 3 weeks of age. In summary, our data show for the first time, the presence of mature osteoblasts in long bones of the limbs despite the complete loss of growth plate formation due to Ihh deficiency. These data indicate an important function for Ihh in regulating limb mesenchymal cell differentiation.
- Published
- 2015
11. Performance status scale for head and neck scores for oral cancer survivors: predictors and factors for improving quality of life
- Author
-
Masaya Okura, Katsuhiko Amano, Takahide Kondo, Tomonao Aikawa, Mikihiko Kogo, Hironobu Kobashi, Akinari Sugauchi, and Yusuke Yabuno
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Trismus ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Cancer Survivors ,Medicine ,Humans ,Survivors ,Head and neck ,General Dentistry ,Aged ,Rehabilitation ,Performance status ,business.industry ,Cancer ,Neck dissection ,030206 dentistry ,medicine.disease ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Physical therapy ,Quality of Life ,Multiple linear regression analysis ,Female ,medicine.symptom ,business - Abstract
This study aimed to determine the factors associated with long-term quality of life of oral cancer survivors. A total of 508 survivors were assessed using the performance status scale for head and neck (PSS-HN), which comprises Eating in Public (E-Public), Normalcy of Diet (N-Diet), and Understandability of Speech (U-Speech). Stepwise multiple linear regression analysis was performed. The median time between the end of treatment and participating in the survey was 38 months (range, 6–250). Overall, 57–60% of survivors achieved full performance (100 score) of each PSS-HN score, whereas 15% had moderate or severe impairment (≤ 50 score) in E-Public and N-Diet, and 4% had impairment in U-Speech. These three scores deteriorated with increasing T-stage. Age, soft tissue reconstruction, trismus, and missing occlusal contacts on the contralateral side were significantly associated with E-Public and N-Diet. Neck dissection, hard tissue reconstruction, and missing occlusal contacts bilaterally were associated with U-Speech score. Older age, T4 tumor, and soft tissue reconstruction were predictors of low E-Public and N-Diet performance scores. Increasing mouth opening and maintaining optimal occlusal contacts on the contralateral side may be effective ways to improve N-Diet and E-Public performance. Maintaining optimal occlusal contacts bilaterally may be effective for improving speech performance. Oral health care to increase optimal occlusal contacts and rehabilitation of trismus may be promising factors to improve the functional performance of oral cancer survivors.
- Published
- 2017
12. A Study Related to the Role of Old standing Companies, Local Government and the Chambers of Commerce and Industry of Revitalizations of Local Economies
- Author
-
Katsuhiko, AMANO, 研究ノート, Note, and 千葉商科大学政策情報学部
- Published
- 2014
13. TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts
- Author
-
Chiaki Yamada, Katsuhiko Amano, Seiji Iida, Emi Okuno, Sosuke Takahata, Kazuaki Miyagawa, Tomonao Aikawa, Mikihiko Kogo, Masaaki Kimata, and Masaya Okura
- Subjects
Cancer Research ,interleukin-1α ,Odontogenic Tumors ,Bone resorption ,Transforming Growth Factor beta1 ,03 medical and health sciences ,0302 clinical medicine ,Stroma ,Osteoclast ,Transforming Growth Factor beta ,Interleukin-1alpha ,medicine ,Tumor Cells, Cultured ,Humans ,Prostaglandin E2 ,receptor activator of NF-κB ligand ,biology ,Cyst Fluid ,odontogenic tumor ,RANK Ligand ,Osteoprotegerin ,keratocystic odontogenic tumor ,transforming growth factor-β ,030206 dentistry ,Articles ,Fibroblasts ,Jaw Neoplasms ,Recombinant Proteins ,Resorption ,medicine.anatomical_structure ,Oncology ,RANKL ,030220 oncology & carcinogenesis ,Odontogenic Cysts ,Cancer research ,biology.protein ,Keratocystic Odontogenic Tumor ,Stromal Cells ,Transforming growth factor ,medicine.drug - Abstract
Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-β (TGF-β), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-κB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1α (IL-1α) signaling and non-COX-2/PGE2 pathway through TGF-β receptor signaling. TGF-β1 and IL-1α produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma.
- Published
- 2016
14. Cleft Lip in Oculodentodigital Dysplasia Suggests Novel Roles for Connexin43
- Author
-
Katsuhiko Amano, Mikihiko Kogo, Masaaki Kimata, Tomonao Aikawa, Akira Murakami, Naoko Kishi, M. Ishiguchi, and Takuro Fujimaki
- Subjects
Male ,Proband ,Heterozygote ,Candidate gene ,Pathology ,medicine.medical_specialty ,Guanine ,Cleft Lip ,Glutamic Acid ,Bone Morphogenetic Protein 4 ,Oculodentodigital dysplasia ,Biology ,Polymorphism, Single Nucleotide ,Epithelium ,TFAP2A ,Fingers ,Mice ,medicine ,Animals ,Humans ,Abnormalities, Multiple ,Eye Abnormalities ,Craniofacial ,General Dentistry ,Tooth Abnormalities ,Adenine ,Lysine ,Infant ,Exons ,Anatomy ,Galactosyltransferases ,medicine.disease ,Introns ,Lip ,stomatognathic diseases ,Transcription Factor AP-2 ,Glucosyltransferases ,Bilateral cleft lip ,Child, Preschool ,Connexin 43 ,Models, Animal ,Immunohistochemistry ,IRF6 - Abstract
Oculodentodigital Dysplasia (ODDD) is a rare syndrome involving anomalies in eye, tooth, and digit formation, caused by mutations in CX43/ GJA1. In addition to classic dental features, ODDD includes oral and craniofacial accessory symptoms such as characteristic facial appearance and cleft palate. However, there have been no reports of ODDD accompanied by cleft lip. Herein we report, for the first time, a male, sporadic, Asian proband presenting bilateral cleft lip. By direct sequence analysis, our proband was diagnosed as having ODDD with a heterozygous mutation, codon 142 G>A in GJA1 and CX43E48K. We excluded the possibility of pathogenic mutations in B3GALTL, BMP4, TFAP2A, PVRL1, IRF6, and MSX1. To address how CX43/ GJA1 is related to cleft lip, we performed immunohistochemistry using mouse and human mid-facial tissue. CX43 expression was detected in the nasal compartment and nasal and maxillary processes at murine developmental stage E12.5. Furthermore, CX43 expression was found in the epithelial tissue inside the human subepithelial cleft lip that completes epithelial fusion. Therefore, we suggest that CX43/ GJA1 is involved in lip formation. Our case report of ODDD with a bilateral cleft lip suggests that CX43/ GJA1 might be a novel candidate gene for syndromic cleft lip.
- Published
- 2012
15. The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9
- Author
-
Kenji Hata, Toshiyuki Yoneda, Shuji Muramatsu, Katsuhiko Amano, Kenji Takada, Riko Nishimura, Yoko Takigawa, Akio Matsuda, Makoto Wakabayashi, and K. Ono
- Subjects
Transcriptional Activation ,endocrine system ,animal structures ,Bone Morphogenetic Protein 2 ,SOX9 ,Biology ,Chondrocyte ,Cell Line ,Mice ,Chondrocytes ,stomatognathic system ,Transcription (biology) ,medicine ,Animals ,Humans ,Genetic Testing ,Transcription factor ,Gene ,Gene Library ,Cell Nucleus ,Gene knockdown ,cDNA library ,Cell Differentiation ,Extremities ,SOX9 Transcription Factor ,Promoter ,Cell Biology ,musculoskeletal system ,Molecular biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Mutation ,embryonic structures ,Protein Binding ,Transcription Factors - Abstract
Sox9 is an essential transcription factor for chondrogenesis by regulating the expression of chondrogenic genes. However, its regulatory mechanism is not fully understood. To address this, we attempted to identify the transcriptional partners of Sox9 by screening the cDNA library of the chondrogenic cell line ATDC5 using the collagen 2α1 (Col2α1) gene promoter fused to a luciferase reporter gene. One of the positive clones encoded the Znf219 gene. Whole mount in situ hybridization experiments indicated that Znf219 mRNA was specifically expressed in the developing limb buds where Col2α1 and Sox9 were strongly expressed. Znf219 markedly enhanced the transcriptional activity of Sox9 on the Col2a1 gene promoter. In addition, Znf219 is physically associated with Sox9 and is colocalized with Sox9 in the nucleus. We also found that overexpression of Znf219 profoundly increased Sox9-induced mRNA expression of Col2a1, aggrecan and Col11a2. Consistently, knockdown of Znf219 decreased the Sox9-induced mRNA expression of these genes. Furthermore, a dominant-negative mutant Znf219 inhibited Bmp2-induced chondrocyte differentiation. Our results suggest that Znf219 plays an important role in the regulation of chondrocyte differentiation as a transcriptional partner of Sox9.
- Published
- 2010
16. Facial frontal morphological changes related to mandibular setback osteotomy using cephalograms
- Author
-
Kenji Takada, Takashi Yamashiro, Seiji Iida, Mikihiko Kogo, Tomonao Aikawa, Takakazu Yagi, and Katsuhiko Amano
- Subjects
Adult ,Male ,Adolescent ,Cephalometry ,medicine.medical_treatment ,Bone Screws ,Oral Surgical Procedures ,Dentistry ,Mandible ,Osteotomy ,Young Adult ,stomatognathic system ,Bone plate ,Humans ,Medicine ,Maxillofacial Development ,Fixation (histology) ,Plate fixation ,business.industry ,Craniometry ,medicine.disease ,Internal Fixators ,Jaw Fixation Techniques ,stomatognathic diseases ,Malocclusion, Angle Class III ,Treatment Outcome ,Otorhinolaryngology ,Face ,Female ,Surgery ,Oral Surgery ,Malocclusion ,business ,Bone Plates ,Follow-Up Studies - Abstract
Summary Aim The purpose of this study was to examine morphological changes of the mandibular region using frontal cephalograms following bilateral sagittal split osteotomy (BSSO) for mandibular setback. Furthermore, we compared the stability between screw and plate fixation. Methods Pre and postoperative frontal cephalograms were taken of 26 patients. Parameters, Angle " A " which is formed by constructed lines along the mandibular ramus, and mandibular width at the angle were calculated. The subjects were analyzed according to the types of bony fixation, whether by screws or plates. Results Angle " A " and mandibular angular width of total numbers did not widely change at early period following operation. Late postoperatively, mandibular width of total numbers decreased in conjunction with increasing Angle " A ". When comparing the parameters between screw and plate groups, the plate group showed a decrease of Angle " A " as an early change. Late postoperatively, the plate group showed an increase of Angle " A " and a decrease of mandibular width, while the screw group had smaller changes. Conclusion We demonstrate postoperative inclination of mandibular lower ramus towards the facial midline. We suggest that the types of rigid fixation have an influence on frontal skeletal morphology, namely that screw fixation has higher stability.
- Published
- 2009
17. A case of post-extraction hemorrhage as a complication of aneurysm-related chronic DIC
- Author
-
Yoshinao Asahi, Mikihiko Kogo, Katsuhiko Amano, Kimiko Nomura, and Shiro Omichi
- Subjects
medicine.medical_specialty ,business.industry ,Hemorrhage as a complication ,medicine.disease ,Surgery ,Fibrinogenolysis ,Aneurysm ,Hemostasis ,Rare case ,Medicine ,Maxillary molar ,Chronic disseminated intravascular coagulation ,Complication ,business - Abstract
Since elderly patients with systemic diseases often undergo tooth extraction, it is difficult to predict the risk of and to optimally treat post-extraction hemorrhage. We report a rare case of persistent hemorrhage that occurred after tooth extraction caused by chronic disseminated intravascular coagulation (DIC) as a complication of dissecting aneurysm. A 69-year-old man who underwent extraction of a maxillary molar had persistent bleeding, which could not be stopped by continuous local treatment to promote hemostasis. After a general examination, we diagnosed chronic DIC caused by an extensive dissecting aneurysm, based on evidence of advanced fibrinogenolysis. Hemostasis was achieved by general treatment for chronic DIC. Appropriate diagnosis and treatment of both local and general conditions are necessary for post-extraction hemorrhage.
- Published
- 2008
18. Functional Gene Screening System Identified TRPV4 as a Regulator of Chondrogenic Differentiation
- Author
-
Satoshi Shiojiri, Riko Nishimura, Sumio Sugano, Katsuhiko Amano, Kosuke Tashiro, Satoru Kuhara, Shuji Muramatsu, Makoto Wakabayashi, Toshiyuki Yoneda, Toshinori Sugahara, Rika Ooishi, Takeshi Ohno, Akio Matsuda, and Yutaka Suzuki
- Subjects
Small interfering RNA ,DNA, Complementary ,Calmodulin ,Cell Culture Techniques ,TRPV Cation Channels ,Biology ,Biochemistry ,Cell Line ,Mice ,Chondrocytes ,Transcription (biology) ,Gene expression ,Animals ,SOX9 Transcription Factor ,Molecular Biology ,Transcription factor ,Gene Library ,Genome ,Activator (genetics) ,High Mobility Group Proteins ,Cell Biology ,Chondrogenesis ,Molecular biology ,embryonic structures ,biology.protein ,Transcription Factors - Abstract
Sox9 is a transcription factor that is essential for chondrocyte differentiation and chondrocyte-specific gene expression. However, the precise mechanism of Sox9 activation during chondrogenesis is not fully understood. To investigate this mechanism, we performed functional gene screening to identify genes that activate SOX9-dependent transcription, using full-length cDNA libraries generated from a murine chondrogenic cell line, ATDC5. Screening revealed that TRPV4 (transient receptor potential vanilloid 4), a cation channel molecule, significantly elevates SOX9-dependent reporter activity. Microarray and quantitative real time PCR analyses demonstrated that during chondrogenesis in ATDC5 and C3H10T1/2 (a murine mesenchymal stem cell line), the expression pattern of TRPV4 was similar to the expression patterns of chondrogenic marker genes, such as type II collagen and aggrecan. Activation of TRPV4 by a pharmacological activator induced SOX9-dependent reporter activity, and this effect was abolished by the addition of the TRPV antagonist ruthenium red or by using a small interfering RNA for TRPV4. The SOX9-dependent reporter activity due to TRPV4 activation was abrogated by both EGTA and a calmodulin inhibitor, suggesting that the Ca2+/calmodulin signal is essential in this process. Furthermore, activation of TRPV4 in concert with insulin activity in ATDC5 cells or in concert with bone morphogenetic protein-2 in C3H10T1/2 cells promoted synthesis of sulfated glycosaminoglycan, but activation of TRPV4 had no effect alone. We showed that activation of TRPV4 increased the steady-state levels of SOX9 mRNA and protein and SOX6 mRNA. Taken together, our results suggest that TRPV4 regulates the SOX9 pathway and contributes to the process of chondrogenesis.
- Published
- 2007
19. Ihh/Gli2 Signaling Promotes Osteoblast Differentiation by Regulating Runx2 Expression and Function
- Author
-
Katsuhiko Amano, Atsuko Shimoyama, Masaki Noda, Masahiro Wada, Kenji Hata, Riko Nishimura, Akira Yamaguchi, Takuma Matsubara, Fumiyo Ikeda, Akira Nifuji, and Toshiyuki Yoneda
- Subjects
musculoskeletal diseases ,animal structures ,Indian hedgehog ,Cellular differentiation ,Kruppel-Like Transcription Factors ,Bone Morphogenetic Protein 2 ,Core Binding Factor Alpha 1 Subunit ,CHO Cells ,Zinc Finger Protein Gli2 ,Biology ,Bone morphogenetic protein ,Bone morphogenetic protein 2 ,Mice ,Cricetulus ,Transforming Growth Factor beta ,Cricetinae ,medicine ,Animals ,Hedgehog Proteins ,Molecular Biology ,Osteoblasts ,musculoskeletal, neural, and ocular physiology ,Cell Differentiation ,Osteoblast ,Articles ,Cell Biology ,Transforming growth factor beta ,musculoskeletal system ,biology.organism_classification ,body regions ,RUNX2 ,medicine.anatomical_structure ,Bone Morphogenetic Proteins ,Cancer research ,biology.protein ,Osteocalcin ,Signal Transduction - Abstract
Genetic and cell biological studies have indicated that Indian hedgehog (Ihh) plays an important role in bone development and osteoblast differentiation. However, the molecular mechanism by which Ihh regulates osteoblast differentiation is complex and remains to be fully elucidated. In this study, we investigated the role of Ihh signaling in osteoblast differentiation using mesenchymal cells and primary osteoblasts. We observed that Ihh stimulated alkaline phosphatase (ALP) activity, osteocalcin expression, and calcification. Overexpression of Gli2- but not Gli3-induced ALP, osteocalcin expression, and calcification of these cells. In contrast, dominant-negative Gli2 markedly inhibited Ihh-dependent osteoblast differentiation. Ihh treatment or Gli2 overexpression also up-regulated the expression of Runx2, an essential transcription factor for osteoblastogenesis, and enhanced the transcriptional activity and osteogenic action of Runx2. Coimmunoprecipitation analysis demonstrated a physical interaction between Gli2 and Runx2. Moreover, Ihh or Gli2 overexpression failed to increase ALP activity in Runx2-deficient mesenchymal cells. Collectively, these results suggest that Ihh regulates osteoblast differentiation of mesenchymal cells through up-regulation of the expression and function of Runx2 by Gli2.
- Published
- 2007
20. Conditional Deletion of Indian Hedgehog in Limb Mesenchyme Results in Complete Loss of Growth Plate Formation but Allows Mature Osteoblast Differentiation
- Author
-
Katsuhiko, Amano, Michael J, Densmore, and Beate, Lanske
- Subjects
Male ,Genotype ,Osteocalcin ,Osteoclasts ,Mice, Transgenic ,Kidney ,Real-Time Polymerase Chain Reaction ,Bone and Bones ,Mesoderm ,Mice ,Chondrocytes ,Animals ,Hedgehog Proteins ,Growth Plate ,In Situ Hybridization ,Cell Proliferation ,Homeodomain Proteins ,Osteoblasts ,Cell Differentiation ,Extremities ,Mesenchymal Stem Cells ,Immunohistochemistry ,Phenotype ,Mutation ,RNA ,Female ,Gene Deletion - Abstract
Indian hedgehog (Ihh) is widely recognized as an essential factor for proper skeletal development. Previous in vivo studies using mutant Ihh mouse models were limited by perinatal lethality or carried out after a growth plate formed. Thus the important role of Ihh in mesenchymal cell differentiation has not been investigated. In this study, we established Prx1-Cre;Ihh(fl/fl) mice to ablate Ihh specifically in limb mesenchyme to allow us to observe the phenotype continuously from prenatal development to 3 weeks of age. Mutant mice displayed severe limb abnormalities characterized by complete lack of secondary ossification center and growth plate, indicating an essential role for Ihh in the development of these structures. Interestingly, we discovered that osteoblast differentiation and bone formation could occur in conditions of deficient Ihh. This is a novel finding that has not been observed because of the early lethality of previous Ihh mutants. Mature osteoblasts expressing osteocalcin could be detected in the center of mutant bones at postnatal day 10 (P10). Osteoclasts and blood vessel formation were also present, suggesting active bone remodeling. Histomorphometric analyses show a significant increase in osteoclast number with no major changes in bone formation rate at 3 weeks of age. Mutant long bones in the limbs were deformed, with cortices comprised of irregular woven bone. Also, there was a marked decrease in gene expression of osteoblastic and osteocytic markers. Moreover, mutant long bones displayed bone dysplasia in which we observed increased osteoclast activity and partially reduced osteoblastic and osteocytic differentiation that lead ultimately to loss of bone structures at 3 weeks of age. In summary, our data show for the first time, the presence of mature osteoblasts in long bones of the limbs despite the complete loss of growth plate formation due to Ihh deficiency. These data indicate an important function for Ihh in regulating limb mesenchymal cell differentiation.
- Published
- 2015
21. Indian Hedgehog Signaling Regulates Transcription and Expression of Collagen Type X via Runx2/Smads Interactions*
- Author
-
Beate Lanske, Michael J. Densmore, Katsuhiko Amano, and Riko Nishimura
- Subjects
medicine.medical_specialty ,Indian hedgehog ,Response element ,Immunoblotting ,Molecular Sequence Data ,Kruppel-Like Transcription Factors ,Chondrocyte hypertrophy ,Core Binding Factor Alpha 1 Subunit ,Zinc Finger Protein Gli2 ,Biochemistry ,Zinc Finger Protein GLI1 ,Chondrocyte ,Cell Line ,Smad1 Protein ,Mice ,Chondrocytes ,GLI1 ,Internal medicine ,Cell Line, Tumor ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Gene Regulation ,Hedgehog Proteins ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,Oncogene Proteins ,Microscopy, Confocal ,biology ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Biology ,biology.organism_classification ,Hedgehog signaling pathway ,Cell biology ,RUNX2 ,body regions ,medicine.anatomical_structure ,Endocrinology ,HEK293 Cells ,Gene Expression Regulation ,COS Cells ,biology.protein ,Trans-Activators ,Collagen Type X ,Protein Binding ,Signal Transduction - Abstract
Indian hedgehog (Ihh) is essential for chondrocyte differentiation and endochondral ossification and acts with parathyroid hormone-related peptide in a negative feedback loop to regulate early chondrocyte differentiation and entry to hypertrophic differentiation. Independent of this function, we and others recently reported independent Ihh functions to promote chondrocyte hypertrophy and matrix mineralization in vivo and in vitro. However, the molecular mechanisms for these actions and their functional significance are still unknown. We recently discovered that Ihh overexpression in chondrocytes stimulated the expression of late chondrocyte differentiation markers and induced matrix mineralization. Focusing on collagen type X (Col10α1) expression and transcription, we observed that hedgehog downstream transcription factors GLI-Kruppel family members (Gli) 1/2 increased COL10A1 promoter activity and identified a novel Gli1/2 response element in the 250-bp basic promoter. In addition, we found that Ihh induced Runx2 expression in chondrocytes without up-regulating other modulators of chondrocyte maturation such as Mef2c, Foxa2, and Foxa3. Runx2 promoted Col10α1 expression in cooperation with Ihh. Further analyses using promoter assays, immunofluorescence, and binding assays showed the interaction of Gli1/2 in a complex with Runx2/Smads induces chondrocyte differentiation. Finally, we could demonstrate that Ihh promotes in vitro matrix mineralization using similar molecular mechanisms. Our data provide an in vitro mechanism for Ihh signaling to positively regulate Col10α1 transcription. Thus, Ihh signaling could be an important player for not only early chondrocyte differentiation but maturation and calcification of chondrocytes.
- Published
- 2014
22. Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes
- Author
-
Kenji Hata, Makoto Wakabayashi, Yoshinobu Maeda, Michiko Yoshida, Robert H. Whitson, Sumio Sugano, Masako Nakanishi, Katsuhiko Amano, Toshiyuki Yoneda, Akio Matsuda, Rikako Takashima, K. Ono, Yutaka Suzuki, and Riko Nishimura
- Subjects
Male ,endocrine system ,animal structures ,General Physics and Astronomy ,SOX9 ,Methylation ,General Biochemistry, Genetics and Molecular Biology ,Chondrocyte ,Histones ,Mice ,Chondrocytes ,stomatognathic system ,Histone demethylation ,Histone H2A ,medicine ,Animals ,Promoter Regions, Genetic ,Transcription factor ,Histone Demethylases ,Mice, Knockout ,Mice, Inbred C3H ,Multidisciplinary ,biology ,SOX9 Transcription Factor ,General Chemistry ,musculoskeletal system ,Chondrogenesis ,Cell biology ,DNA-Binding Proteins ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Histone ,Gene Expression Regulation ,embryonic structures ,biology.protein ,NIH 3T3 Cells ,Demethylase ,Female ,Protein Binding ,Transcription Factors - Abstract
Histone modification, a critical step for epigenetic regulation, is an important modulator of biological events. Sox9 is a transcription factor critical for endochondral ossification; however, proof of its epigenetic regulation remains elusive. Here we identify AT-rich interactive domain 5b (Arid5b) as a transcriptional co-regulator of Sox9. Arid5b physically associates with Sox9 and synergistically induces chondrogenesis. Growth of Arid5b(-/-) mice is retarded with delayed endochondral ossification. Sox9-dependent chondrogenesis is attenuated in Arid5b-deficient cells. Arid5b recruits Phf2, a histone lysine demethylase, to the promoter region of Sox9 target genes and stimulates H3K9me2 demethylation of these genes. In the promoters of chondrogenic marker genes, H3K9me2 levels are increased in Arid5b(-/-) chondrocytes. Finally, we show that Phf2 knockdown inhibits Sox9-induced chondrocyte differentiation. Our findings establish an epigenomic mechanism of skeletal development, whereby Arid5b promotes chondrogenesis by facilitating Phf2-mediated histone demethylation of Sox9-regulated chondrogenic gene promoters.
- Published
- 2013
23. Long-term Follow-up of an Advanced Adult Periodontitis Case with Bite Collapse
- Author
-
Eijiro Maki, Shingo Minoura, Ikuko Watanabe, Koji Inagaki, Motoyasu Murase, Katsuhiko Amano, Toshihide Noguchi, Miki Suzuki, and Yumi Tsukamoto
- Subjects
Adult periodontitis ,Long term follow up ,business.industry ,medicine ,Dentistry ,medicine.symptom ,business ,Collapse (medical) - Published
- 1996
24. Five Years of Clinical Evaluation of Nonresorbable Membranes in the Treatment of Intrabony Defects Following Guided Tissue Regeneration
- Author
-
Masanori Koide, Tamaki Nagira, Nobuo Yoshinari, Saeko Nishiyama, Koji Inagaki, Toshihide Noguchi, Tosyo Tohya, Katsuhiko Amano, Hiroki Suzuki, Atsushi Mori, and Kazuhiro Ishikawa
- Subjects
medicine.medical_specialty ,Membrane ,business.industry ,medicine ,business ,Clinical evaluation ,Surgery - Abstract
GTR法の5年間の臨床的評価を行うために, 成人性歯周炎を有する患者28名に対して14名14部位 (年齢21から57歳, 平均40.9歳の男性3名, 女性11名の14名) に組織再生誘導法 (GTR群), 14名14部位 (年齢23から54歳, 平均39.6歳の男性5名, 女性9名の14名) に歯肉剥離掻爬術 (FOP群) を行った。GTR群の被験部位の骨欠損形態は, 1壁性骨欠損1部位, 2壁性骨欠損11部位, 3壁性骨欠損2部位であった。FOP群の被験部位の骨欠損形態は, 1壁性骨欠損2部位, 2壁性骨欠損9部位, 3壁性骨欠損3部位であった。術前, 術後5年の臨床所見から, 歯周ボクット (PD) の減少量はGTR群3.9±1.6mm, FOP群2.9±1.5 mmであり, 臨床的アタッチメントレベル (CAL) の獲得量はGTR群3.2±1.8mm, FOP群1.1±1.4mmであり, 歯肉退縮量 (MR) は, GTR群0.7±1.3mm, FOP群1.8±1.5mmであった。GTR群の術前, 術後5年のCALに有意な改善を認めた。また, CALの獲得量は, GTR群がFOP群と比べて有意な増加を示した。さらに術後1年と5年の間の両群のPD, CALは安定していた。以上より, 5年間にわたってGTR群のPD, CALは安定しており, 有用であることが示唆された。
- Published
- 1996
25. Studies on Clinical and Microbiological Evaluation of Minocycline Hydrochloride with a Local Drug Delivery System in the Acute Phase of Adult Periodontitis
- Author
-
Yoshihiro Morita, Masanori Koide, Midori Ohshima, Mitsuo Fukuda, Nobuo Ueda, Kazuhiro Ishikawa, Taneaki Nakagawa, Takaho Kuroyanagi, Satoru Yamada, Tetsuo Takada, Toshihide Noguchi, Yuichi Ishihara, Hideto Sakai, Nobuo Yoshinari, Saeko Nishiyama, Atsushi Mori, Akihiro Asai, Hidekazu Kitamura, Katsuhiko Amano, Motoyasu Murase, and Koji Inagaki
- Subjects
Adult periodontitis ,business.industry ,Drug delivery ,Dentistry ,Medicine ,Minocycline Hydrochloride ,business - Abstract
本研究では, 歯周ポケット底部への到達性に優れ, 塩酸ミノサイクリンを含有し, 投与直後より徐々に局所で溶解するストリップスタイプの薬剤の歯周炎の急性症状に対する局所投与の臨床的・細菌学的研究を行った。対象とした患者は, 歯周病の急性症状を呈し, 全身的疾患を有さず過去3ケ月以内に抗生物質の投与を受けていない43名とした。43名全てに歯周炎局所由来の痛みを伴う発赤・腫脹または膿瘍形成が認められた。塩酸ミノサイクリン含有のストリップスを歯周ポケット底部にまで挿入した。ストリップスを挿入後, 0, 3, 7日後の臨床症状の変化を観察し, 細菌学的変化を0, 7日後に観察した。歯肉の発赤, 腫脹, 疼痛, プロービング深さ (probing depth, PD), プロービング時出血 (bleeding on probing, BOP), 排膿 (suppuration, S), リンパ節所見および歯肉溝滲出液 (gingival crevicular fluid, GCF) 量の変化を記録した。黒色色素産生性グラム陰性嫌気性桿菌 (Black Pigmented Gram-Negative Anaerobic Rods, BPNAR) 数, 生菌数は非選択性血液平板培地で生育させて測定した。疼痛, 腫脹 (口腔内), BOPおよびSは, 薬剤投与後3日目および7日目で投与開始時に比較して有意に減少していた。さらに, PDおよびGCF量においても7日目において有意な減少が観察された。投与前に優勢であったBPNARの構成比率は投与開始直前と比較し, 7日後では明らかに減少していた。これらの結果から, 歯周ポケット内への塩酸ミノサイクリン含有ストリップスの局所投与は, 歯周炎の急性症状の改善に有効であることが示唆された。
- Published
- 1995
26. Studies on Clinical and Microbiological Evaluation of a Strip Type Drug Containing Minocycline Hydrochloride for Periodontitis. Comparative Study with Minocycline Hydrochloride Dental Ointment
- Author
-
Haruyoshi Fujishiro, Katsuhiko Amano, Tamaki Nagira, Satsuki Hagiwara, Shozo Yamada, Toshihide Noguchi, Yoshiko Nakashima, Isao Ishikawa, Masaki Kaneyama, Yasunari Ohshima, Mitsuo Fukuda, Norimitsu Shirozu, Kazuyuki Noguchi, Yasuo Yamada, Hisashi Watanabe, Akihiro Asai, Eijiro Maki, Keiko Takada, Eita Shimada, Makoto Umeda, Naoko Murase, Toyoyuki Tamura, and Hirohisa Hayakawa
- Subjects
Periodontitis ,Drug ,business.industry ,media_common.quotation_subject ,medicine ,Dentistry ,Minocycline Hydrochloride ,business ,medicine.disease ,media_common - Abstract
現在, 歯肉縁下プラークのコントロール法のひとつとして, 抗生物質の歯周ポケット内投与が行われている。今回われわれは, 歯周ポケット底部への到達性に優れ, 塩酸ミノサイクワンを含有し, 投与直後より徐々に局所で溶解 (ローカルドラッグデリバリーシステム) するストリップスタイプの薬剤 (Strip type Drug for Periodontitis: SDP) の臨床効果を既存の歯科用塩酸ミノサイクリン軟膏 (Periocline ® : PER) と比較検討した。対象とした患者は, 全身疾患がなく, 4mm以上の歯周ポケットを有する歯周炎の症状を呈し, 過去3カ月以内に抗生物質の投与を受けていない68人とし, SDPを33人に, またPERを35人に局所投与した。投与は1週毎に4回連続投与した。7週後まで臨床症状の変化を観察し, 併せて細菌検査を培養法によって行った。細菌検査実施時期は薬剤投与開始時および4週後 (薬剤投与終了1週後) とした。臨床症状の観察項目は, プロービングデプス (probing depth: PD), プロービング時出血 (bleeding on probing: BOP), 排膿 (suppuration: S), 歯垢指数 (plaque index: PlI), 歯肉炎指数 (gingival index: GI) および歯肉溝滲出液 (gingival crevicular fluid: GCF) 量の変化とした。細菌はPorphyromonas gingivalis, Prevotella intermedia, Prevotella melaninogenica, Fusoacteriumz nucleatum, Eikenella corrodens, Capnocytophaga spp., Actinobacillus a ctinomycetemcomitansの7菌種を選択培地等で分離・検索し, 黒色色素産生性グラム陰性i嫌気性桿菌数, 生菌数は非選択性血液平板培地で生育させて測定した。その結果, BOP, S, GI, およびPDにおいて, 投与開始時と比較して3週後, 4週後および7週後で, 両群とも有意な減少が認められた。GCFではPER群のみ全観察期間において有意な減少が認められた。また, 臨床主要症状の改善度では両群ともに高い有効率を示したが, 両群問に有意な差は認められなかった。細菌学的検索において黒色色素産生性グラム陰性嫌気性桿菌数の変化, 生菌数の変化ともに投与の前後で有意な減少が認められ, 両群間で有意差は認められなかった。さらに上記7菌種別の消失率をみても両群問に有意な差は認められず, 両薬剤とも各菌種に対して有効であった。塩酸ミノサイクリンの局所投与における臨床的・細菌学的効果を調べたところ, 良好な結果が得られた。また, 剤型の違いによる比較を行ったところ, 臨床的・細菌学的効果に大きな差は認められず, ともに有効であることが示された。
- Published
- 1995
27. Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription
- Author
-
Yoko Takigawa, Riko Nishimura, Katsuhiko Amano, K. Ono, Toshiyuki Yoneda, Shuji Muramatsu, Masako Nakanishi, Mikihiko Kogo, Makoto Wakabayashi, Rikako Takashima, Akio Matsuda, and Kenji Hata
- Subjects
musculoskeletal diseases ,Transcriptional Activation ,Cell Physiology ,Cellular differentiation ,Recombinant Fusion Proteins ,Gene Expression ,SOX9 ,Cartilage metabolism ,Biology ,Chondrocyte ,Adenoviridae ,Cell Line ,Tripartite Motif Proteins ,Mice ,Chondrocytes ,Organ Culture Techniques ,Luciferases, Firefly ,Gene expression ,medicine ,Escherichia coli ,Animals ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,Collagen Type II ,Cell Proliferation ,Gene Library ,Activator (genetics) ,Intracellular Signaling Peptides and Proteins ,Promoter ,Cell Differentiation ,SOX9 Transcription Factor ,Cell Biology ,Articles ,musculoskeletal system ,Embryo, Mammalian ,Molecular biology ,medicine.anatomical_structure ,Cartilage ,Female ,Carrier Proteins ,Chondrogenesis ,Plasmids ,Protein Binding - Abstract
This study shows that Arid5a interacts with Sox9 and subsequently modulates histone 3 acetylation of a chondrogenic gene, Col2a1, and stimulates chondrocyte differentiation., SRY-box–containing gene 9 (Sox9) is an essential transcription factor in chondrocyte lineage determination and differentiation. Recent studies demonstrated that Sox9 controls the transcription of chondrocyte-specific genes in association with several other transcriptional regulators. To further understand the molecular mechanisms by which Sox9 influences transcriptional events during chondrocyte differentiation, we attempted to identify transcriptional partners of Sox9 and to examine their roles in chondrocyte differentiation. We isolated AT-rich interactive domain–containing protein 5a (Arid5a; also known as Mrf1) as an activator of the Col2a1 gene promoter from an ATDC5 cDNA library. Arid5a was highly expressed in cartilage and induced during chondrocyte differentiation. Furthermore, Arid5a physically interacted with Sox9 in nuclei and up-regulated the chondrocyte-specific action of Sox9. Overexpression of Arid5a stimulated chondrocyte differentiation in vitro and in an organ culture system. In contrast, Arid5a knockdown inhibited Col2a1 expression in chondrocytes. In addition, Arid5a binds directly to the promoter region of the Col2a1 gene and stimulates acetylation of histone 3 in the region. Our results suggest that Arid5a may directly interact with Sox9 and thereby enhance its chondrocyte-specific action.
- Published
- 2011
28. Sox9 family members negatively regulate maturation and calcification of chondrocytes through up-regulation of parathyroid hormone-related protein
- Author
-
Kenji Hata, Toshiyuki Yoneda, Atsushi Sugita, Mikihiko Kogo, Yoko Takigawa, Katsuhiko Amano, Riko Nishimura, K. Ono, and Makoto Wakabayashi
- Subjects
medicine.medical_specialty ,animal structures ,Cellular differentiation ,Kruppel-Like Transcription Factors ,SOX9 ,Biology ,Zinc Finger Protein Gli2 ,Chondrocyte ,Cell Line ,Tissue Culture Techniques ,Mice ,Calcification, Physiologic ,Chondrocytes ,Internal medicine ,medicine ,Animals ,Hedgehog Proteins ,Molecular Biology ,Endochondral ossification ,Transcription factor ,Parathyroid hormone-related protein ,Parathyroid Hormone-Related Protein ,Cell Differentiation ,SOX9 Transcription Factor ,Cell Biology ,Articles ,Chondrogenesis ,musculoskeletal system ,Cell biology ,Endocrinology ,medicine.anatomical_structure ,embryonic structures ,Signal transduction ,SOXD Transcription Factors ,Signal Transduction - Abstract
Sox9 is a transcription factor that plays an essential role in chondrogenesis and has been proposed to inhibit the late stages of endochondral ossification. However, the molecular mechanisms underlying the regulation of chondrocyte maturation and calcification by Sox9 remain unknown. In this study, we attempted to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6 (Sox5/6/9) inhibited the maturation and calcification of murine primary chondrocytes and up-regulated parathyroid hormone–related protein (PTHrP) expression in primary chondrocytes and the mesenchymal cell line C3H10T1/2. Sox5/6/9 stimulated the early stages of chondrocyte proliferation and development. In contrast, Sox5/6/9 inhibited maturation and calcification of chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter region of the PTHrP gene and up-regulated PTHrP gene promoter activity. Interestingly, we also found that the Sox9 family members functionally collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte differentiation. Our results provide novel evidence that Sox9 family members mediate endochondral ossification by up-regulating PTHrP expression in association with Ihh/Gli2 signaling.
- Published
- 2009
29. Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice
- Author
-
Toshiyuki Yoneda, Kenji Hata, Riko Nishimura, Katsuhiko Amano, Fumiyo Ikeda, Akio Matsuda, Vincent R. Harley, Takuma Matsubara, and Shuji Muramatsu
- Subjects
Transcription, Genetic ,Cellular differentiation ,Amino Acid Motifs ,Biology ,Models, Biological ,Chondrocyte ,Mice ,Nuclear Matrix-Associated Proteins ,medicine ,Animals ,Humans ,SOX9 Transcription Factor ,Promoter Regions, Genetic ,Transcription factor ,Regulation of gene expression ,Gene knockdown ,High Mobility Group Proteins ,RNA-Binding Proteins ,Paraspeckle ,Cell Differentiation ,General Medicine ,Chondrogenesis ,musculoskeletal system ,Molecular biology ,medicine.anatomical_structure ,Gene Expression Regulation ,embryonic structures ,Mutation ,RNA ,Research Article ,HeLa Cells ,Transcription Factors - Abstract
The Sox9 transcription factor plays an essential role in promoting chondrogenesis and regulating expression of chondrocyte extracellular-matrix genes. To identify genes that interact with Sox9 in promoting chondrocyte differentiation, we screened a cDNA library generated from the murine chondrogenic ATDC5 cell line to identify activators of the collagen, type II, alpha 1 (Col2a1) promoter. Here we have shown that paraspeckle regulatory protein 54-kDa nuclear RNA-binding protein (p54nrb) is an essential link between Sox9-regulated transcription and maturation of Sox9-target gene mRNA. We found that p54nrb physically interacted with Sox9 and enhanced Sox9-dependent transcriptional activation of the Col2a1 promoter. In ATDC5 cells, p54nrb colocalized with Sox9 protein in nuclear paraspeckle bodies, and knockdown of p54(nrb) suppressed Sox9-dependent Col2a1 expression and promoter activity. We generated a p54nrb mutant construct lacking RNA recognition motifs, and overexpression of mutant p54nrb in ATDC5 cells markedly altered the appearance of paraspeckle bodies and inhibited the maturation of Col2a1 mRNA. The mutant p54nrb inhibited chondrocyte differentiation of mesenchymal cells and mouse metatarsal explants. Furthermore, transgenic mice expressing the mutant p54nrb in the chondrocyte lineage exhibited dwarfism associated with impairment of chondrogenesis. These data suggest that p54nrb plays an important role in the regulation of Sox9 function and the formation of paraspeckle bodies during chondrogenesis.
- Published
- 2008
30. Repeated distraction osteogenesis for excessive vertical alveolar augmentation: a case report
- Author
-
Seiji, Iida, Tamaki, Nakano, Katsuhiko, Amano, and Mikihiko, Kogo
- Subjects
Adult ,Radiography ,Retreatment ,Osteogenesis, Distraction ,Humans ,Female ,Alveolar Ridge Augmentation ,Mandible - Abstract
In this article, a procedure involving 2-stage alveolar distraction osteogenesis using eccentric distraction devices for the augmentation of resorbed transplanted iliac bone following mandibular tumor resection is presented. A 6-month consolidation period was allowed between the first and second distractions, and endosseous implants were placed 4 months after the second distraction. Computerized tomographic images obtained before the implantation revealed that, 10 months after the first distraction, the bone generated still showed lower density compared with the basal bone, but the bone from both distractions showed enough maturity for implantation. It may be concluded that 2-stage alveolar distraction osteogenesis can be a useful and safe procedure for excessive alveolar lengthening if a sufficiently long consolidation period is allowed.
- Published
- 2006
31. PP090
- Author
-
Tomonao Aikawa, Chiaki Yamada, Katsuhiko Amano, Kazuaki Miyagawa, Emi Okuno, Masaaki Kimata, Masaya Okura, and Mikihiko Kogo
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Stromal cell ,biology ,Odontogenic tumor ,medicine.disease ,Bone resorption ,Oncology ,Odontogenic cyst ,RANKL ,biology.protein ,medicine ,Keratocystic Odontogenic Tumor ,Cyst ,Oral Surgery ,Ameloblastoma - Abstract
Purpose Odontogenic tumor and odontogenic cyst, arising in jaw bone, grow with resorption and destruction of jaw bones. However, the mechanisms of bone resorption by odontogenic tumor and cyst are still unclear. These odontogenic lesions consist of odontogenic epithelial cells and stromal fibroblasts. It has been demonstrated that odontogenic epithelial cells of developing tooth germ induce osteoclastogenesis to prevent tooth germ from invasion of developing bone. Thus we hypothesized that odontogenic epithelial cells in odontogenic tumor and cyst induce osteoclastogenesis, and then that would play potential roles in tumor outgrowth into the jaw bones. Purpose of this study is to examine osteoclastogenesis by cytokines, focusing on TGF-b, produced by odontogenic epithelial cells. Results Concentration of TGF-b in fluids of odontogenic tumor and cyst (ameloblastoma, keratocystic odontogenic tumor and follicular cyst) was measured by ELISA, and expression of TGF-b, were examined by immunohistochemistry. Expression of RANKL, OPG and COX-2 in stromal fibroblasts in culture was assessed by RT-PCR and/or western blotting, and PGE2 synthesis was measured by ELISA. Fluids of jaw tumor and cyst increased expression of RANKL in stromal fibroblasts isolated from odontogenic tumor, but did not change expression of OPG. Induction of RANKL expression was further enhanced by acidified fluids. The induction of RANKL by the fluids was inhibited by SB-505124, a selective inhibitor of TGF-b receptor kinase or anti TGF-b neutralizing antibody, suggesting the fluids contain TGF-b. Immunohistochemistry revealed that TGF-b was positive in epithelial cells of odontogenic tumor/cyst, and phosphorylated smad3 was localized in the nuclei of odontogenic epithelial cells and stromal fibroblasts. TGF-b induced RANKL expression in the presence of cycloheximide, a protein synthesis inhibitor. Conclusions These results suggest that TGF-b signals directly enhanced RANKL gene transcription in stromal fibroblast, and then induced-RANKL would be participate in bone resorption by the lesions.
- Published
- 2013
32. Involvement of the NMDA-nitric oxide pathway in the development of hypersensitivity to tactile stimulation in dental injured rats
- Author
-
Katsuhiko Amano, Norifumi Yonehara, and Yoshinori Kamisaki
- Subjects
Male ,Pain Threshold ,medicine.medical_specialty ,N-Methylaspartate ,Nitric Oxide Synthase Type I ,Nitric Oxide ,Receptors, N-Methyl-D-Aspartate ,Trigeminal Nuclei ,Nitric oxide ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Enzyme Inhibitors ,Receptor ,Pain Measurement ,Pharmacology ,Sensory stimulation therapy ,omega-N-Methylarginine ,Behavior, Animal ,business.industry ,Tooth Injuries ,Immunohistochemistry ,Rats ,stomatognathic diseases ,Endocrinology ,Allodynia ,chemistry ,Hyperalgesia ,Touch ,Anesthesia ,Dental surgery ,Nitric Oxide Pathway ,Injections, Intravenous ,NMDA receptor ,medicine.symptom ,Dizocilpine Maleate ,Nitric Oxide Synthase ,business ,Injections, Intraperitoneal - Abstract
To investigate mechanisms in pathological pain conditions as the hyperalgesia and allodynia observed after dental surgery, we employed a rat dental-injury model involving the simultaneous pulpectomy to a lower incisor and extraction of an ipsilateral upper incisor. We found that hypersensitivity to tactile stimulation developed on both ipsilateral and contralateral sides in the dental-injured rats 5 days after the surgery and that this lasted for at least 30 days. Recovery from hypersensitivity to tactile stimulation was achieved by the intraperitoneal (i.p.) administration of MK-801 (0.05 mg/kg) or N(G)-monomethyl-L-arginine monoacetate (L-NMMA: 10 - 100 mg/kg), but not attained by N(G)-monomethyl-D-arginine monoacetate (D-NMMA: 100 mg/kg). This recovery effect of L-NMMA (50 mg/kg) was inhibited by pretreatment with L-arginine (600 mg/kg). In the trigeminal nucleus caudalis (SpVc), the changes in nitric oxide (NO) levels invoked by the intravenous (i.v.) administration of N-methyl-D-aspartate (NMDA; 10 mg/kg) were found to be significantly larger in the dental-injured rats than in sham-operated rats. The number of neuronal NO synthase (nNOS)-positive neurons increased in layers I-II and III-IV in the SpVc on both sides of the dental-injured rats. These results suggest that hypersensitivity to tactile stimulation developed following dental injury, and that NMDA receptor/NOS/NO production pathways in the SpVc may be involved in pathological conditions.
- Published
- 2002
33. 142 FUNCTIONAL ANALYSIS OF TRPV4 DURING CHONDROGENESIS
- Author
-
T. Ohno, Katsuhiko Amano, R. Nishimura, A. Matsuda, Makoto Wakabayashi, S. Muramatsu, and T. Yoneda
- Subjects
TRPV4 ,Rheumatology ,Functional analysis ,Chemistry ,Biomedical Engineering ,Orthopedics and Sports Medicine ,Chondrogenesis ,Cell biology - Published
- 2008
34. Regulation of endochondral ossification by transcription factors
- Author
-
K. Ono, Yoko Takigawa, Toshiyuki Yoneda, Makoto Wakabayashi, Kenji Hata, Katsuhiko Amano, Rikako Takashima, and Riko Nishimura
- Subjects
medicine.medical_specialty ,Cartilage metabolism ,Biology ,Models, Biological ,Chromatin remodeling ,Chondrocytes ,Osteogenesis ,Transcription (biology) ,Internal medicine ,medicine ,Animals ,Humans ,Transcription factor ,Endochondral ossification ,Bone Development ,SOX9 Transcription Factor ,Endoplasmic Reticulum Stress ,Chondrogenesis ,Cell biology ,Cartilage ,Endocrinology ,Histone ,Unfolded protein response ,biology.protein ,Signal Transduction ,Transcription Factors - Abstract
Endochondral ossification is very unique and complex biological event which is associated with skeletal development and tissue partnering. Genetic studies and gene-targeting approaches identified several transcription factors that play important roles in endochondral ossification. These transcription factors sequentially and harmoniously regulate each step of endochondral ossification, and consequently maintain the spatio-temporal control of the program. Importantly, these transcription factors form large protein complex to control chromatin remodeling, histone modification, transcription and splicing steps during endochondral ossification. It is also important to understand how these transcription factors regulate expression of their target genes. Biochemical and molecular cloning techniques largely contributed to identification of the components of the transcriptional complex and the target genes. Most recently, importance of endoplasmic reticulum (ER) stress in endochondral ossification has been reported. A transcription factor, BBF2H7, functions as an ER stress sensor in chondrocytes through regulation of appropriate secretion of chondrogenic matrices. We would like to discuss how the transcription factors regulate endochondral ossification.
- Published
- 2012
35. Transcription factor Dmrt2 (double-sex and mab-3 related transcription factor 2) controls endochondral ossification by inhibiting early chondrogenesis and promoting late chondrogenesis
- Author
-
K. Ono, Eriko Nakamura, Masako Nakanishi, Toshiyuki Yoneda, Katsuhiko Amano, Atsushi Sugita, Yoko Takigawa, Riko Nishimura, and Kenji Hata
- Subjects
Histology ,Physiology ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine ,Biology ,Monoclonal antibody ,Chondrogenesis ,Transcription factor ,Endochondral ossification ,Cell biology - Published
- 2009
36. A transcription factor Znf219 regulates chondrogenesis by forming a transcription factory complex with Sox9
- Author
-
Katsuhiko Amano, Riko Nishimura, Toshiyuki Yoneda, K. Ono, Yoko Takigawa, A. Matsuda, S. Muramatsu, Makoto Wakabayashi, Kenji Takada, and Kenji Hata
- Subjects
Histology ,biology ,General transcription factor ,Physiology ,Chemistry ,Endocrinology, Diabetes and Metabolism ,Response element ,Cell biology ,Sp3 transcription factor ,biology.protein ,GATA transcription factor ,Transcription factor II F ,Transcription factor II E ,Transcription factor II D ,Transcription factor II A - Published
- 2009
37. Indian Hedgehog Signaling Regulates Transcription and Expression of Collagen Type X via Runx2/Smads Interactions.
- Author
-
Katsuhiko Amano, Michael Densmore, Riko Nishimura, and Beate Lanske
- Subjects
- *
HEDGEHOG signaling proteins , *CARTILAGE cells , *ENDOCHONDRAL ossification , *IMMUNOFLUORESCENCE , *COLLAGEN - Abstract
Indian hedgehog (Ihh) is essential for chondrocyte differentiation and endochondral ossification and acts with parathyroid hormone-related peptide in a negative feedback loop to regulate early chondrocyte differentiation and entry to hypertrophic differentiation. Independent of this function, we and others recently reported independent Ihh functions to promote chondrocyte hypertrophy and matrix mineralization in vivo and in vitro. However, the molecular mechanisms for these actions and their functional significance are still unknown. We recently discovered that Ihh overexpression in chondrocytes stimulated the expression of late chondrocyte differentiation markers and induced matrix mineralization. Focusing on collagen type X (Col10α1) expression and transcription, we observed that hedgehog downstream transcription factors GLI-Krüppel family members (Gli) 1/2 increased COL10A1 promoter activity and identified a novel Gli1/2 response element in the 250-bp basic promoter. In addition, we found that Ihh induced Runx2 expression in chondrocytes without up-regulating other modulators of chondrocyte maturation such as Mef2c, Foxa2, and Foxa3. Runx2 promoted Col10α1 expression in cooperation with Ihh. Further analyses using promoter assays, immunofluorescence, and binding assays showed the interaction of Gli1/2 in a complex with Runx2/Smads induces chondrocyte differentiation. Finally, we could demonstrate that Ihh promotes in vitro matrix mineralization using similar molecular mechanisms. Our data provide an in vitro mechanism for Ihh signaling to positively regulate Col10α1 transcription. Thus, Ihh signaling could be an important player for not only early chondrocyte differentiation but maturation and calcification of chondrocytes. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
38. Signal transduction and transcriptional regulation during mesenchymal cell differentiation.
- Author
-
Riko Nishimura, Kenji Hata, Fumiyo Ikeda, Fumitaka Ichida, Atsuko Shimoyama, Takuma Matsubara, Masahiro Wada, Katsuhiko Amano, and Toshiyuki Yoneda
- Published
- 2008
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.