Faculty Profiles - Amano Katsuhiko

A case of epidermoid cyst considered as originated from the abdominal skin tissue inserted into the temporomandibular joint 52 years ago Reviewed

Soma Kato, Katsuhiko Amano, Norifumi Moritani, Yuki Nagata, Natsuki Segami, Seiji Iida

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 36 ( 3 ) 354 - 358 2024.5

Pth1r in Neural Crest Cells Regulates Nasal Cartilage Differentiation Reviewed

K. Amano, D. Okuzaki, Y. Kitaoka, S. Kato, M. Fujiwara, S. Tanaka, S. Iida

Journal of Dental Research 103 ( 3 ) 308 - 317 2024.3

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications

Neural crest cells (NCC) arise from the dorsal margin of the neural plate border and comprise a unique cell population that migrates to and creates the craniofacial region. Although factors including Shh, Fgf8, and bone morphogenetic proteins have been shown to regulate these biological events, the role of parathyroid hormone 1 receptor (Pth1r) has been less studied. We generated an NCC-specific mouse model for Pth1r and researched gene expression, function, and interaction focusing on nasal cartilage framework and midfacial development. Wnt1-Cre;Pth1r^{fl/ fl}; Tomato^fl/+ mice had perinatal lethality, but we observed short snout and jaws, tongue protrusion, reduced NCC-derived cranial length, increased mineralization in nasal septum and hyoid bones, and less bone mineralization at interfrontal suture in mutants at E18.5. Importantly, the mutant nasal septum and turbinate cartilage histologically revealed gradual, premature accelerated hypertrophic differentiation. We then studied the underlying molecular mechanisms by performing RNA seq analysis and unexpectedly found that expression of Ihh and related signaling molecules was enhanced in mutant nasomaxillary tissues. To see if Pth1r and Ihh signaling are associated, we generated a Wnt1-Cre; Ihh^{fl/ fl}; Pth1r^{fl/ fl}; Tomato^fl/+ (DKO) mouse and compared the phenotypes to those of each single knockout mouse: Wnt1-Cre; Ihh^{fl/ fl}; Pth1r^fl/+; Tomato^fl/+ (Ihh-CKO) and Wnt1-Cre;Ihh^fl/+; Pth1r^{fl/ fl}; Tomato^fl/+ (Pth1r-CKO). Ihh-CKO mice displayed a milder effect. Of note, the excessive hypertrophic conversion of the nasal cartilage framework observed in Pth1r-CKO was somewhat rescued DKO embryos. Further, a half cAMP responsive element and the 4 similar sequences containing 2 mismatches were identified from the promoter to the first intron in Ihh gene. Gli1-Cre^ERT2; Pth1r^{fl/ fl}; Tomato^fl/+, a Pth1r-deficient model targeted in hedgehog responsive cells, demonstrated the enlarged hypertrophic layer and significantly more Tomato-positive chondrocytes accumulated in the nasal septum and ethmoidal endochondral ossification. Collectively, the data suggest a relevant Pth1r/Ihh interaction. Our findings obtained from novel mouse models for Pth1r signaling illuminate previously unknown aspects in craniofacial biology and development.

DOI： 10.1177/00220345231221954

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/00220345231221954

放射線性顎骨壊死18例における感染源と周術期口腔管理の効果についての検討 Reviewed

武田斉子, 水川展吉, 田村庄平, 中田靖章, 天野克比古, 浅海淳一, 飯田征二

岡山大学歯学会雑誌 42 ( 2 ) 23 - 32 2023.12

Pth1r Signal in Gli1+ Cells Maintains Postnatal Cranial Base Synchondrosis Reviewed

K. Amano, Y. Kitaoka, S. Kato, M. Fujiwara, D. Okuzaki, T. Aikawa, M. Kogo, S. Iida

Journal of Dental Research 102 ( 11 ) 1241 - 1251 2023.10

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Cranial base synchondroses are the endochondral ossification centers for cranial base growth and thus indispensable for proper skull, brain, and midfacial development. The synchondroses are composed of mirror-image growth plates that are continuously maintained from the embryonic to postnatal stage through chondrocyte differentiation. Several factors, including Pth1r signaling, are known to control fetal synchondrosis development. However, there are currently no reports regarding any role for Pth1r signaling in postnatal cranial base and synchondrosis development. Also, the mesenchymal cells that source Pth1r signaling for synchondroses are not known. Here, we employed an inducible mouse model, a hedgehog-responsive Gli1-CreERT2 driver, focusing on the postnatal study. We performed 2 inducible protocols using Gli1-CreERT2;Tomatofl/+ mice that uncovered distinct patterning of Gli1-positive and Gli1-negative chondrocytes in the synchondrosis cartilage. Moreover, we generated Gli1-CreERT2;Pth1rfl/fl;Tomatofl/+ mice to assess their functions in postnatal synchondrosis and found that the mutants had survived postnatally. The mutant skulls morphologically presented unambiguous phenotypes where we noticed the shortened cranial base and premature synchondrosis closure. Histologically, gradual disorganization in mutant synchondroses caused an uncommon remaining central zone between hypertrophic zones on both sides while the successive differentiation of round, flat, and hypertrophic chondrocytes was observed in control sections. These mutant synchondroses disappeared and were finally replaced by bone. Of note, the mutant fusing synchondroses lost their characteristic patterning of Gli1-positive and Gli1-negative chondrocytes, suggesting that loss of Pth1r signaling alters the distribution of hedgehog-responsive chondrocytes. Moreover, we performed laser microdissection and RNA sequencing to characterize the flat proliferative and round resting chondrocytes where we found flat chondrocytes have a characteristic feature of both chondrocyte proliferation and maturation. Taken together, these data demonstrate that Pth1r signaling in Gli1-positive cells is essential for postnatal development and maintenance in cranial base synchondroses. Our findings will elucidate previously unknown aspects of Pth1r functions in cranial biology and development.

DOI： 10.1177/00220345231184405

Scopus

開窓術により治療した舌下型類皮嚢胞の１例 Reviewed

武田斉子, 田村庄平, 天野克比古, 水川展吉, 高畠清文, 飯田征二

日本口腔外科学会雑誌 69 ( 10 ) 475 - 480 2023.10

Mandibular condylar displacement and the associated factors following intraoral vertical ramus osteotomy Reviewed

Yuki Nagata, Norifumi Moritani, Katsuhiko Amano, Yuki Arimura, Kazuki Nakatsuji, Soma Kato, Ayaka Mikami, Tatsushi Matsumura, Seiji Iida

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 35 ( 5 ) 390 - 396 2023.9

A sporadic case of Gigantiform Cementoma with mild and atypical clinical manifestation. Reviewed

Kasahara S, Amano K, Kurioka K, Minohara M, Kogo M, Tanaka S

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 35 ( 3 ) 233 - 240 2023.5

A case of a massive Desmoplastic Fibroblastoma on the mandibular gingiva. Reviewed

Yasuda T, Amano K, Kawamura K, Cho J, Kogo M, Tanaka S

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 35 ( 2 ) 172 - 177 2023.3

Osteonecrosis of the Jaw in Two Rheumatoid Arthritis Patients Not Treated with a Bisphosphonate Reviewed

Amano K, Sugauchi A, Yamada C, Kogo M, Iida S

Acta Medica Okayama 77 ( 1 ) 111 - 116 2023.2

The secondary case of melanotic neuroectodermal tumor in the infant maxilla: Long-term observation after the enucleation. Reviewed

Kurioka K, Amano K, Harada K, Okura M, Kogo M, Tanaka S

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 34 ( 5 ) 599 - 604 2022.9

Effects of Mechanical Stress and Deficiency of Dihydrotestosterone or 17β-Estradiol on Temporomandibular Joint Osteoarthritis in Mice Reviewed

Tomohisa Ootake, Takenobu Ishii, Kenji Sueishi, Akira Watanabe, Yoichi Ishizuka, Katsuhiko Amano, Masashi Nagao, Kazuaki Nishimura, Yasushi Nishii

Osteoarthritis and Cartilage 29 ( 11 ) 1575 - 1589 2021.11

Indian hedgehog in craniofacial neural crest cells links to skeletal malocclusion by regulating associated cartilage formation and gene expression Reviewed

Katsuhiko Amano, Daisuke Okuzaki, Tomonao Aikawa, Mikihiko Kogo

FASEB Journal 34 ( 5 ) 6791 - 6807 2020.5

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

© 2020 Federation of American Societies for Experimental Biology 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.

DOI： 10.1096/fj.201903269R

Scopus

Performance status scale for head and neck scores for oral cancer survivors: predictors and factors for improving quality of life. Reviewed

Kondo T., Sugauchi A., Yabuno Y., Kobashi H., Amano K., Aikawa T., Kogo M., Okura M.

Clin Oral Investig. 23 ( 4 ) 1575 - 1582 2019.4

A case of modified Furlow palatoplasty applied to a Campomelic dysplasia patient Reviewed

Amano K, Otsuki K, Kurioka K, Fujiwara M, Kogo M

Journal of Oral and Maxillofacial Surgery, Medicine and Pathology 31 ( 2 ) 81 - 85 2019.3

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

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.

DOI： 10.1016/j.ajoms.2018.07.007

非定型口腔顔面裂に対し顔面形成術と口蓋形成術を行った1例 Reviewed

小橋寛薫, 大槻浩一, 磯村恵美子, 原田丈司, 天野克比古, 古郷幹彦

日本口腔外科学会雑誌 64 ( 7 ) 434 - 438 2018.7

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(公社)日本口腔外科学会

症例は生後17日の男児で、出生時に顔面異常を認めたためNICUへ搬送入院となった。両側斜顔面裂、口蓋裂および右側眼球形成不全を認めた。非定形口蓋裂を伴う両側性斜顔面裂の診断で、生後3ヵ月時に全身麻酔下にて顔面、口唇および口角形成術を行った。右側痕跡眼球に関しては、眼球様組織の摘出および角膜、結膜縫合を行い、偽眼ステントを挿入した。1歳時に非定形口蓋裂に対して、Furlow変法を用いた口蓋形成術を行った。3歳時に、創部瘢痕の除去および形態修正術を全身麻酔下にて行い、6歳時に左側の反対咬合と上顎歯列弓の狭窄に対して、緩徐拡大装置を用いた矯正治療を開始した。7歳となる現在、明らかな鼻咽腔閉鎖不全や発音障害もなく経過観察および矯正科にて矯正治療を行っている。

Klotho expression in osteocytes regulates bone metabolism and controls bone formation Reviewed

Hirotaka Komaba, Jovana Kaludjerovic, Dorothy Z. Hu, Kenichi Nagano, Katsuhiko Amano, Noriko Ide, Tadatoshi Sato, Michael J. Densmore, Jun-ichi Hanai, Hannes Olauson, Teresita Bellido, Tobias E. Larsson, Roland Baron, Beate Lanske

KIDNEY INTERNATIONAL 92 ( 3 ) 599 - 611 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

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.

DOI： 10.1016/j.kint.2017.02.014

TGF-beta in jaw tumor fluids induces RANKL expression in stromal fibroblasts Reviewed

Yamada C., Aikawa T., Okuno E., Miyagawa K., Amano K., Takahata S., Kimata M., Okura M., Iida S., Kogo M.

International journal of oncology 49 ( 2 ) 499 - 508 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

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-beta (TGF-beta), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-kappa B ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1 alpha (IL-1 alpha) signaling and non-COX-2/PGE2 pathway through TGF-beta receptor signaling. TGF-beta 1 and IL-1 alpha produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma.

DOI： 10.3892/ijo.2016.3548

Ihh and PTH1R signaling in limb mesenchyme is required for proper segmentation and subsequent formation and growth of digit bones Reviewed

Katsuhiko Amano, Michael Densmore, Yi Fan, Beate Lanske

BONE 83 256 - 266 2016.2

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

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 In, 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. (c) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bone.2015.11.017

Conditional Deletion of Indian Hedgehog in Limb Mesenchyme Results in Complete Loss of Growth Plate Formation but Allows Mature Osteoblast Differentiation Reviewed

Katsuhiko Amano, Michael J. Densmore, Beate Lanske

JOURNAL OF BONE AND MINERAL RESEARCH 30 ( 12 ) 2262 - 2272 2015.12

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

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 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 or 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. (C) 2015 American Society for Bone and Mineral Research.

DOI： 10.1002/jbmr.2582