Maintenance and disturbance of osteonetwork: basic studies on clarification of pathophysiology of craniofacial bone diseases

2012 Fiscal Year Final Research Report

• Project/Area Number: 22249061
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YAMAGUCHI Akira 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (00142430)
• Co-Investigator(Kenkyū-buntansha): IIMURA Tadahiro 東京医科歯科大学, 歯と骨の GCOE 拠点, 准教授 (20282775) ; SAKAMOTO Kei 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (00302886) ; TAMAMURA Sadahiro 東京医科歯科大学, 大学院・医歯学総合研究科, 特認助教 (70431963)
• Project Period (FY): 2010 – 2012
• Keywords: 骨芽細胞 / 骨細胞 / 破骨細胞 / 口腔癌 / 骨破壊

Research Abstract

We conducted experiments to clarify the pathophysiology of craniofacial bone diseases based on the concept of osteonetwork, and the following results were published. 1. Development of bioimaging techniques to visualize the netwrork among osteoblasts, osteocytes and osteoclasts. 2. Osteocytes play crucial roles in orthodontic tooth movement. 3.CCN3 is a negative regulator in bone regeneration. $. RANKL plays crucial roles in bone destruction induced by oral squamous cell carcinoma.

Research Products

• [Journal Article] Spatiotemporal disorder in endochondral ossification during axial skeleton development in the Mesp2-null mouse: A developmental etiology of spondylocostal dysostosis and spondylothoracic dysostosis (2013)
  • Author(s): Makino Y, Takahashi Y, Tanabe R, Tamamura Y, Watanabe T, Haraikawa M, Hamagaki M, Hata K, Kanno J, Yoneda T, Saga Y,Goseki-Sone M, Kaneko K, Yamaguchi A, Iimura T
  • Journal Title: BONE Volume: 53 Pages: 248-258
• [Journal Article] The role of osteocytes in bone resorption during orthodontic tooth movement (2013)
  • Author(s): Matsumoto T, Iimura T, Ogura K, Moriyama K, Yamaguchi A
  • Journal Title: J Dent Res Volume: 92 Pages: 340-345
• [Journal Article] The expression profiles of acidic epithelial keratins in Ameloblastoma (2013)
  • Author(s): Pal KS, Sakamoto K, Aragaki T, Akashi T, Yamaguchi A
  • Journal Title: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology Volume: 115 Pages: 523-531
• [Journal Article] RANKL synthesized by both stromal cells and cancer cells plays a crucial role in osteoclastic bone resorption induced by oral cancer (2013)
  • Author(s): Sato K, Lee JW, Sakamoto K, Iimura T, Kayamori K, Yasuda H, Shindoh M, Ito M, Omura K, Yamaguchi A
  • Journal Title: Amer J Pathol Volume: 182 Pages: 1890-1899
• [Journal Article] Structural differences in the osteocyte network between the calvaria and long bone revealed by three-dimensional fluorescence morphometry, possibly reflecting distinct mechano-adaptations and sensitivities (2012)
  • Author(s): Himeno-Ando A, Izumi Y, Yamaguchi A, Iimura T
  • Journal Title: Biochem Bioph Res Co Volume: 417 Pages: 765-770
• [Journal Article] Reduction of NOTCH1 expression pertains to maturation abnormalities of keratinocytes in squamous neoplasms (2012)
  • Author(s): Sakamoto K, Fujii T, Kawachi H, Miki Y, Omura K, Morita K, Kayamori K, Khanom R, Katsube K, Yamaguchi A
  • Journal Title: Lob Invest Volume: 92 Pages: 688-702
• [Journal Article] Expression of basal cell keratin 15 and keratin 19 in oral squamous cell carcinoma represent diverse phthophysiologies (2012)
  • Author(s): Khanom R, Sakamoto K, Pal SK, Shimada Y, Morita K-i, Omura K, Miki Y, Yamaguchi A
  • Journal Title: Histol Histopathol Volume: 27 Pages: 949-959
• [Journal Article] Cdc42 is required for chondrogenesis and interdigital programmed cell death during limb development (2012)
  • Author(s): Aizawa R, Yamada A, Suzuki D, Iimura T, Kassai H, Harada T, Tsukasaki M, Yamamoto G, Tachikawa T, Nakao K, Yamamoto M, Yamaguchi A, Aiba A, Kamijo R
  • Journal Title: Mech Dev Volume: 129 Pages: 38-50
• [Journal Article] Clinical significance of lymphatic and blood vessel invasion in oral tongue squamous cell carcinomas (2012)
  • Author(s): Michikawa C, Uzawa N, Kayamori K, Sonoda I, Ohyama Y, Okada N, Yamaguchi A, Amagasa T
  • Journal Title: Oral Oncol Volume: 48 Pages: 320-324
• [Journal Article] Canine oral mucosal fibroblasts differentiate into osteoblastic cellsin response to BMP-2 (2012)
  • Author(s): Umehara K,Iimura T,Sakamoto K,Lin Z,Kasugai S,Igarashi Y,Yamaguchi A
  • Journal Title: Anat Rec Volume: 295 Pages: 1327-1335
• [Journal Article] Increasing participation of Sclerostin in postnatal bone development revealed by three-dimensional immunofluorescence morphometry (2012)
  • Author(s): Watanabe T, Tamamura Y, Hoshino A, Makino Y, Nishimura R, Kamioka H, Yoneda T, Amagasa T, Yamaguchi A, Iimura T
  • Journal Title: BONE Volume: 51 Pages: 447-458
• [Journal Article] Ectopic production of hair keratin constitutes Rushton's hyaline bodies in association with hematogenous deposits (2012)
  • Author(s): Sakamoto K, Khanom R, Hamagaki M, Yamaguchi A
  • Journal Title: J Oral Pathol Med Volume: 27 Pages: 949-959
• [Journal Article] CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction. (2012)
  • Author(s): Oue E, Lee JW, Sakamoto K, Iimura T, Aoki K, Kayamori K, Michi Y, Yamashiro M,Yamaguchi A
  • Journal Title: Biochem Bioph Res Co Volume: 424 Pages: 456-461
• [Journal Article] Osterix regulates calcification and degradation of chondrogenic matrices through matrix metalloproteinase (MMP13) expression in association with transcription factor Runx2 during endochondral ossification (2012)
  • Author(s): Nishimura R, Wakabayashi M, Hata K, Matsubara T, Honma H, Wakisaka S, Kiyonari H, Shioi G, Yamaguchi A, Tsumaki N, Akiyama H, Yoneda T
  • Journal Title: J Biol Chem Volume: 287 Pages: 33179-33190
• [Journal Article] Roles of chemokine receptor CX3CR1 in maintaining murine bone homeostasis through the regulation of both osteoblasts and osteoclasts (2012)
  • Author(s): Hoshino A, Ueha S, Hanada S, Imai T, Ito M, Yamamoto K, Matsushima K, Yamaguchi A, Iimura T
  • Journal Title: J Cell Sci Volume: 258 Pages: 28826-28837
• [Journal Article] Retention of bone strength by feeding of milk and dairy products in ovariectomized rats; involvement of changes in serum levels of 1alpha, 25(OH)2D3 and FGF23 (2012)
  • Author(s): Tanabe R, Haraikawa M, Sogabe N,Sugimoto A, Kawamura Y, Takasugi S, Nagata M, Nakane A, Yamaguchi A, Iimura T, Masae Goseki-Sone
  • Journal Title: J Nutr Biochem Volume: 2012 [Epub ahead of print] 10.1016/j.jnutbio Pages: 004
• [Journal Article] Effects of veraguensin and galgravin on osteoclast differentiation and function (2012)
  • Author(s): Asai M, Lee JW, Itakura Y, Choi BK, Yonezawa T, Teruya T, Cha BY, Ohnishi M, Yamaguchi A, Woo JT
  • Journal Title: Cytotechnology Volume: 64 Pages: 315-322
• [Journal Article] A fluorescence spotlight on the clockwork development and metabolism of bone (2012)
  • Author(s): Iimura T, Nakane A, Sugiyama M, Sato H, Makino Y, Watanabe T, Takagi Y, Numano R, Yamaguchi A
  • Journal Title: J Bone Miner Metab Volume: 30 Pages: 254-269
• [Journal Article] Down-regulation ofkeratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelialdysplasia: a clue for histopathogenesis (2011)
  • Author(s): Sakamoto K, Aragaki T, Kawachi H, KatsubeK, Miki Y, Takizawa T, Omura K, Morita K,Okada N, Yamaguchi A
  • Journal Title: Histopathol Volume: 58 Pages: 531-542
• [Journal Article] Acerogenin A, a natural compound isolated from Acer nikoense Maxim,stimulates osteoblast differentiation through bone morphogenetic protein action (2011)
  • Author(s): Kihara K, Ichikawa S, Yonezawa T, Lee JW,Akihisa T, Woo JT, Michi Y, Amagasa T, Yamaguchi A
  • Journal Title: Biochem Bioph Res Co Volume: 406 Pages: 211-217
• [Journal Article] Comparative morphology of osteocytes in aquatic and land vertebrates (2011)
  • Author(s): Cao L, Moriishi T, Miyazaki T, Iimura T, Tamamura S, Komori T, Yamaguchi A
  • Journal Title: J Bone Miner Metab Volume: 29 Pages: 662-670
• [Journal Article] TGF-β drivesepithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP (2011)
  • Author(s): Horiguchi K, Sakamoto K, Koinuma D,Semba K, Inoue A, Inoue S, Fujii H,Yamaguchi A, Miyazawa K, Miyazono K, Saitoh M
  • Journal Title: Oncogene Volume: 31 Pages: 3190-3201
• [Journal Article] Illumination of vertebrate development by fluorescence live imaging (2011)
  • Author(s): Iimura T, Sugiyama M, Makino Y, Nakane A, Watanabe T, Yamaguchi A
  • Journal Title: Cytometry Research Volume: 21 Pages: 57-63
• [Journal Article] Roles of IL-6 and PTHrP in osteoclast formation associated with oral cancers:The significance of IL-6 synthesized by stromal cells in response to cancer cells (2010)
  • Author(s): Kayamori K, Sakamoto K, Nakashima T,Takayanagi T, Morita K, Omura K, Nguyen ST,Miki Y, Iimura T, Himeno A, Akashi T, Yamada-Okabe H, Ogata E, Yamaguchi A
  • Journal Title: Amer JPathol Volume: 176 Pages: 968-980
• [Journal Article] Repetition ofcontinuous PTH treatments followed byperiodic withdrawals exerts anabolic effects on rat bone (2010)
  • Author(s): Etoh M, Yamaguchi A
  • Journal Title: J Bone Miner Metab Volume: 28 Pages: 641-649
• [Journal Article] Deficiency of chemokine receptor CCR1 causesosteopenia due to impaired functions of osteoclasts and osteoblasts (2010)
  • Author(s): Hoshino A, Iimura T, Ueha S, Hanada S, Maruoka Y, Mayahara M, Suzuki K, Imai T,Ito M, Manome Y, Yasuhara M, Kirino T, Yamaguchi A, Matsushima K, Yamamoto K
  • Journal Title: J Biol Chem Volume: 285 Pages: 28826-28837
• [Journal Article] Comprehensive keratin profiling reveals distinctions between keratocysticodontogenic tumor and orthokeratinized odontogenic cyst (2010)
  • Author(s): Aragaki T, Michi Y, Katsube K, Uzawa N,Okada N, Akashi T, Amagasa T, Yamaguchi A,Sakamoto K
  • Journal Title: Human Pathol Volume: 42 Pages: 1718-1725
• [Journal Article] Maf mediates the age-related switch in mesenchymal cell (2010)
  • Author(s): Nishikawa K, Isogai M, Nakashima T, TakedaS, Michito, Hamada M, Kimura A, Kodama T, Yamaguchi A, Owen MJ, Takahashi S,Takayanagi H
  • Journal Title: J Clin Invest Volume: 120 Pages: 3455-3465
• [Journal Article] Hox genes, a molecular constraint for development and evolution of vertebrate bodyplan (2010)
  • Author(s): Iimura T, Himeno A, Nakane A, YamaguchiA
  • Journal Title: J Oral Biosci Volume: 52 Pages: 155-163
• [Journal Article] CCN3 participates in bone regeneration as an inhibitory factor
  • Author(s): Matsushita Y, Sakamoto K, Tamamura Y, Shibata Y, Minamizato T, Kihara T, Ito M, Katsube K, Hiraoka S, Koseki H, Harada K, Yamaguchi A
  • Journal Title: J Biol Chem Volume: (in press)
• [Presentation] 顎骨壊死の最新情報 (2013)
  • Author(s): 山口朗
  • Organizer: 第5回口腔先端応用科学研究会
  • Place of Presentation: 日本大学会館大講堂(招待講演)
  • Year and Date: 2013-01-26
• [Presentation] 病理組織学的立場から見たBMA関連顎骨病変の成因と診断、口腔三学会合同シンポジウム、「Bone-modifying Agents (BMA)関連顎骨病変の病態・診断・治療」 (2012)
  • Author(s): 山口朗
  • Organizer: 第57回日本口腔外科学会総会・学術大会、パシフィコ横浜会議センター
  • Year and Date: 2012-10-20
• [Presentation] オステオネットワークの維持と破綻:骨疾患の病態解明を目指して (2012)
  • Author(s): 山口朗
  • Organizer: 第27回長崎骨粗鬆症研究会、長崎県医師会館
  • Place of Presentation: 長崎
  • Year and Date: 2012-05-09
• [Presentation] オステオネットワークの獲得・維持・破綻 (2012)
  • Author(s): 山口朗
  • Organizer: 米田俊之教授退官記念講演会、大阪大学中之島センター
  • Place of Presentation: 大阪
  • Year and Date: 2012-05-05
• [Presentation] Bisphosphonate-related osteonecrosis, updates (2012)
  • Author(s): Yamaguchi A
  • Organizer: 2012 Sino-Japan Dental Conference
  • Place of Presentation: Chengdu, Sichaun, China
  • Year and Date: 2012-04-27
• [Presentation] 顎骨壊死の病態の最新知見 (2012)
  • Author(s): 山口朗
  • Organizer: 第10回日本歯科骨粗鬆症研究会、シンポジウム「ビスフォスフォネート製剤の長期治療による光と影-顎骨壊死は回避できるのかー」
  • Place of Presentation: 大阪
  • Year and Date: 2012-03-18
• [Presentation] オステオネットワークの維持と破壊:顎骨疾患の病態解明と新たな治療法の開発を目指して (2012)
  • Author(s): 山口朗
  • Organizer: 第30回北海道医療大学歯学会、特別講演
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-03
• [Presentation] 口腔癌の骨破壊、第30回日本口腔腫瘍学会 (2012)
  • Author(s): 山口朗
  • Organizer: 教育講演
  • Place of Presentation: 大宮
  • Year and Date: 2012-01-27
• [Presentation] Bone destruction by oral cancer (2012)
  • Author(s): Yamaguchi A
  • Organizer: The 6th Global COE international Symposium at TMDU
  • Place of Presentation: Tokyo
  • Year and Date: 2012-01-22
• [Presentation] インプラントをみすえた骨の形態学的解析;骨のリモデリングを中心として (2011)
  • Author(s): 山口朗
  • Organizer: Dentistry, Ouo Vadis?, 特別講演
  • Place of Presentation: 東京
  • Year and Date: 2011-12-10
• [Presentation] 口腔癌による骨破壊の分子メカニズム、口腔三学会合同シンポジウム「顎骨浸潤を伴う口腔癌の病態・診断・治療」 (2011)
  • Author(s): 山口朗
  • Organizer: 第56回に本口腔外科学会総会・学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2011-10-22
• [Presentation] オステオネットワークの構築・維持・破壊 (2011)
  • Author(s): 山口 朗
  • Organizer: 第41回骨・カルシウム代謝研究会(特別講演)
  • Place of Presentation: ホテルグランビィア京都
  • Year and Date: 2011-10-14
• [Presentation] Role of BMP, Notch, and CCN3 in osteoblast differentiation and bone regeneration. Lecture (2011)
  • Author(s): Yamaguchi A
  • Organizer: International Summer Program 2011
  • Place of Presentation: Tokyo Medical and Dental University, Tokyo
  • Year and Date: 2011-08-30
• [Presentation] Histopathological characteristics of bisphosphonate-related osteomyelitis (osteonecrosis) of jaw. Keynote Lecture (2011)
  • Author(s): Yamaguchi A
  • Organizer: 5th Meeting of Asian Society of Oral and Maxillofacial Pathology
  • Place of Presentation: Fukuoka
  • Year and Date: 2011-08-24
• [Presentation] Molecular mechanism of bone destruction by oral cancer (2011)
  • Author(s): Yamaguchi A
  • Organizer: The Second Chinese National Conference on Oral Maxillofacial Development and Regeneration
  • Place of Presentation: Wuyishan city, Fujian Province, China
  • Year and Date: 2011-07-29
• [Presentation] 血管石灰化と骨・軟骨関連因子、シンポジウム:CDKにおける異所性石灰化:基礎と臨床 (2011)
  • Author(s): 山口朗
  • Organizer: 第56回日本透析医学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-06-18
• [Presentation] ビスフォスフォネート関連顎骨壊死(骨髄炎)の病理学的所見、シンポジウム (2011)
  • Author(s): 山口朗
  • Organizer: 第31回日本骨形態計測学会
  • Place of Presentation: 岐阜
  • Year and Date: 2011-05-20
• [Presentation] 骨再生の分子基盤(シンポジウム:骨の再生医療) (2011)
  • Author(s): 山口朗
  • Organizer: 第65回日本口腔科学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-04-15
• [Presentation] ビスホスホネート関連顎骨壊死(骨髄炎)、(シンポジウム:難治性骨髄炎の治療戦略) (2011)
  • Author(s): 山口朗
  • Organizer: 第65回日本口腔科学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-04-14
• [Presentation] Molecular mechanism ofbone destruction by oral squamouscells carcinoma (2011)
  • Author(s): Yamaguchi A
  • Organizer: The Firstinternational Oral Pathology UpdateSymposium
  • Place of Presentation: Taipei
  • Year and Date: 2011-03-27
• [Presentation] 再生医療「骨再生」-そのメ カニズムと応用- (2011)
  • Author(s): 山口朗
  • Organizer: 平成22年日本歯科医師会生涯研修セミナー
  • Place of Presentation: 京都
  • Year and Date: 2011-03-06
• [Presentation] オステオネットワークの維持と破綻:骨再生の分子基盤を中心として (2011)
  • Author(s): 山口朗
  • Organizer: 第11回産学連携フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2011-02-28
• [Presentation] 骨再生のメカニズムと骨再生療法、招待講演、DENTISTRY, QUOVADIS? (2010)
  • Author(s): 山口朗
  • Organizer: 東京(野口英世記念会館)
  • Place of Presentation: 東京
  • Year and Date: 2010-12-05
• [Presentation] 骨代謝の基礎と骨再生、特別講演 (2010)
  • Author(s): 山口朗
  • Organizer: 平成22年度日本小児歯科学会秋期大会、郡山市民文化センター
  • Place of Presentation: 郡山
  • Year and Date: 2010-12-02
• [Presentation] オステオネットワークの維持と破綻:顎顔面骨疾患の病態解明を目指して、教育講演 (2010)
  • Author(s): 山口朗
  • Organizer: 第58回 NPO 法人日本口腔科学会中国・四国地方部会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-06
• [Presentation] 再生医療「骨再生」-そのメカニズムと応用- (2010)
  • Author(s): 山口朗
  • Organizer: 平成22年日本歯科医師会生涯研修セミナー
  • Place of Presentation: 岡山
  • Year and Date: 2010-10-31
• [Presentation] 再生医療「骨再生」-そのメカニズムと応用- (2010)
  • Author(s): 山口朗
  • Organizer: 平成22年日本歯科医師会生涯研修セミナー
  • Place of Presentation: 東京
  • Year and Date: 2010-09-23
• [Presentation] 歯科領域における再生研究の現状:骨・歯の再生を中心に (2010)
  • Author(s): 山口朗
  • Organizer: 第24回東京医科歯科大学大学院セミナー
  • Place of Presentation: 東京
  • Year and Date: 2010-07-26
• [Presentation] 骨形成と血管石灰化の共通点と相違点、シンポジウム「Bone andVascular Calcification」 (2010)
  • Author(s): 山口朗
  • Organizer: 第28回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Presentation] 再生医療「骨再生」-そのメカニズムと応用- (2010)
  • Author(s): 山口朗
  • Organizer: 平成22年日本歯科医師会生涯研修セミナー
  • Place of Presentation: 高松
  • Year and Date: 2010-07-04
• [Presentation] 口腔癌の顎骨浸潤メカニズム (2010)
  • Author(s): 山口朗
  • Organizer: 九州歯科大学大学院セミナー
  • Place of Presentation: 小倉
  • Year and Date: 2010-07-03
• [Presentation] 再生医療「骨再生」-そのメカニズムと応用- (2010)
  • Author(s): 山口朗
  • Organizer: 平成22年日本歯科医師会生涯研修セミナー
  • Place of Presentation: 津、三重県
  • Year and Date: 2010-06-27
• [Presentation] ビスフォスフォネート関連顎骨壊死(骨髄炎)の病理 (2010)
  • Author(s): 山口朗
  • Organizer: 市民公開シンポジウム「ビスフォスフォネート系製剤に起因した顎骨骨髄炎・顎骨壊死の現状と対策」、日本学術会議主催、第64回日本口腔科学会学術集会共催
  • Place of Presentation: 札幌
  • Year and Date: 2010-06-25
• [Presentation] 再生医療「骨再生」-そのメ カニズムと応用- (2010)
  • Author(s): 山口朗
  • Organizer: 平成22年日本歯科医師会生涯研修セミナー
  • Place of Presentation: 水戸
  • Year and Date: 2010-05-23
• [Presentation] ビスフォスフォネート関連顎骨壊死の病理 (2010)
  • Author(s): 山口朗
  • Organizer: 東京都臨床整形外科医会統合研修会(招待講演)
  • Place of Presentation: 東京
  • Year and Date: 2010-05-15
• [Book] IL-6 (2013)
  • Author(s): 山口朗
  • Total Pages: 136-140
  • Publisher: 最新の骨粗鬆症学-骨粗鬆症の最新知見-、日本臨床社
• [Book] BMA(Bone-modifying agents)による顎骨壊死 (2013)
  • Author(s): 山口朗
  • Publisher: 口腔外科ハンドマニュアル2013、(日本口腔外科学会編)、クインテッセンス出版株式会社
• [Book] 血管石灰化と骨・軟骨関連因子 (2012)
  • Author(s): 山口朗
  • Total Pages: 133-138
  • Publisher: 変革する透析医学、医薬ジャーナル社
• [Book] 骨生物医学の新たな潮流;オス テオネットワークの獲得・維持・破綻 (2012)
  • Author(s): 山口朗
  • Total Pages: 107-118
  • Publisher: 口腔と全身の健康、医歯薬出版株式会社