Identification of regulatory molecules for osteogenic activity of BMP.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20592184
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Showa University
• Principal Investigator: KAMIJO Ryutaro Showa University, 歯学部, 教授 (70233939)
• Research Collaborator: KATAGIRI Takenonu 埼玉医科大学, 医学部, 教授 (80245802) ; MIYAMOTO Youichi 昭和大学, 歯学部, 准教授 (20295132) ; TAKAMI Masamichi 昭和大学, 歯学部, 講師 (80307058) ; YAMADA Atsushi 昭和大学, 歯学部, 講師 (50407558)
• Project Period (FY): 2008 – 2010
• Keywords: BMP / マイクロアレイ / 再生 / 硬組織

Research Abstract

Bone morphogenetic proteins (BMPs) regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP-2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation, but inhibits myogenic differentiation in C2C12 cells. To evaluate important genes for BMP-2-induced osteoblast differentiation, we performed cDNA microarray analysis between BMP-2 treated and untreated C2C12 cells, and identified Alx3 (aristaless like homeobox 3) as a gene that was clearly induced during osteoblast differentiation. Alx3 is a homeobox gene related to the Drosophila aristaless gene and a group of vertebrate genes that includes Prx1/2, Cart1 and Alx4. Alx3 is expressed in frontonasal head mesenchyme and the first and second pharyngeal arches. Alx3 has been linked to developmental functions in craniofacial structures and limb development. Little is known about its direct relationship with bone formation. In the present study, we also focused on the mechanisms of Alx3 gene expression and function during osteoblast differentiation induced by BMP-2.

Research Products

• [Journal Article] Enhancement of bone morphogenetic protein-2-induced ectopic bone formation by transforming growth factor-β1. (2011)
  • Author(s): Tachi K, Takami M, Sato H, Mochizuki A, Zhao B, Miyamoto Y, Tsukasaki H, Inoue T, Shintani S, Koike T, Honda Y, Suzuki O, Baba K, Kamijo R
  • Journal Title: Tissue Eng Part A 17 Pages: 597-606
• [Journal Article] 破骨細胞分化の制御機構 (2011)
  • Author(s): 高見正道,上條竜太郎
  • Journal Title: 生化学 83 Pages: 110-114
• [Journal Article] Experience dictates stem cell fate in the adult hippocampus. (2011)
  • Author(s): Dranovsky A, Picchini AM, Moadel T, Yamada A, Kimura S, Leonardo ED, Hen R
  • Journal Title: Neuron (in press)
• [Journal Article] Overview : molecular regulation of mineralization and its failure from disclosure of mechanisms to clinical implications (2010)
  • Author(s): Miyamoto Y, Kamijo R
  • Journal Title: J Oral Biosci 52 Pages: 1-5
• [Journal Article] Bone morphogenetic protein 2 enhances mouse osteoclast differentiation via increased levels of receptor activator of NF-κB ligand expression in osteoblasts. (2010)
  • Author(s): Tachi K, Takami M, Zhao B, Mochizuki A, Yamada A, Miyamoto Y, Inoue T, Baba K, Kamijo R
  • Journal Title: Cell Tissue Res 342 Pages: 213-220
• [Journal Article] The characteristics of in vitro biological activity of titanium surfaces anodically oxidized in chloride solutions. (2010)
  • Author(s): Shibata Y, Suzuki D, Omori S, Tanaka R, Murakami A, Kataoka Y, Baba K, Kamijo R, Miyazaki T
  • Journal Title: Biomaterials 31 Pages: 8546-8555
• [Journal Article] Carbonic anhydrase II regulates differentiation of ameloblasts via intracellular pH-dependent JNK signaling pathway. (2010)
  • Author(s): Wang X, Suzawa T, Ohtsuka H, Zhao B, Miyamoto Y, Miyauchi T, Nishimura R, Inoue T, Nakamura M, Baba K, Kamijo R
  • Journal Title: J Cell Physiol 225 Pages: 709-719
• [Journal Article] Dual roles of SMAD proteins in the conversion from myoblasts to osteoblastic cells by bone morphogenetic proteins. (2010)
  • Author(s): Nojima J, Kanomata K, Takada Y, Fukuda T, Kokabu S, Ohte S, Takada T, Yamamoto TS, Sasanuma H, Yoneyama K, Ueno N, Okazaki Y, Kamijo R, Yoda T, Katagiri T
  • Journal Title: J Biol Chem 285 Pages: 15577-15586
• [Journal Article] The enhanced characteristics of osteoblast adhesion to photofunctionalized nanoscale TiO_2 layers on biomaterials surfaces. (2010)
  • Author(s): Miyauchi T, Yamada M, Yamamoto A, Iwasa F, Suzawa T, Kamijo R, Baba K, Ogawa T
  • Journal Title: Biomaterials 31 Pages: 3827-3839
• [Journal Article] 磁場下プログラムフリーザーを用いた歯髄細胞の凍結保存に関する研究 (2010)
  • Author(s): 増田宜子,大場崇史,山田嘉重,藤島昭宏,宮本洋一,木村祐一,上條竜太郎
  • Journal Title: 日本歯科保存学雑誌 53 Pages: 274-280
• [Journal Article] Honokiol inhibits osteoclast differentiation and function in vitro. (2010)
  • Author(s): Hasegawa S, Yonezawa T, Ahn JY, Cha BY, Teruya T, Takami M, Yagasaki K, Nagai K, Woo JT.
  • Journal Title: Biol Pharm Bull 33(3) Pages: 487-92
• [Journal Article] IFN-γ down-regulates Secretoglobin 3A1 gene expression. (2009)
  • Author(s): Yamada A, Suzuki D, Miyazono A, Oshima K, Kamiya A, Zhao B, Takami M, Donnelly RP, Itabe H, Yamamoto M, Kimura S, Kamijo R
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 964-968
• [Journal Article] Cold preservation of the liver with oxygenation by a two-layer method (2009)
  • Author(s): Odaira M, Aoki T, Miyamoto Y, Yasuhara R, Jin Z, Yu J, Nishino N, Yamada K, Kusano T, Hayashi K, Yasuda D, Koizumi T, Mitamura K, Enami Y, Niiya T, Murai N, Kato H, Shimizu Y, Kamijyo R, Kusano M
  • Journal Title: J Surg Res 152 Pages: 209-217
• [Journal Article] Osteoclast differentiation induced by synthetic octacalcium phosphate through receptor activator of NF-κB ligand expression in osteoblasts. (2009)
  • Author(s): Takami M, Mochizuki A, Yamada A, Tachi K, Zhao B, Miyamoto Y, Anada T, Honda Y, Inoue T, Nakamura M, Suzuki O, Kamijo R
  • Journal Title: Tissue Eng Part A 15 Pages: 3991-4000
• [Journal Article] Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. (2009)
  • Author(s): Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M
  • Journal Title: Pediatr Dent J 19 Pages: 220-227
• [Journal Article] Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development. (2009)
  • Author(s): Suzuki D, Yamada A, Amano T, Yasuhara R, Kimura A, Sakahara M, Tsumaki N, Takeda S, Tamura M, Nakamura M, Wada N, Nohno T, Shiroishi T, Aida A, Kamijo R
  • Journal Title: Dev Biol 335 Pages: 396-406
• [Journal Article] Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis. (2009)
  • Author(s): Zhao B, Takami M, Yamada A, Wang X, Koga T, Hu X, Tamura T, Ozato K, Choi Y, Ivashkiv B. L, Takayanagi H, Kamijo R
  • Journal Title: Nat Med 15 Pages: 1066-1071
• [Journal Article] Lysine- specific gingipain promotes lipo- polysaccharide- and active-vitamin D_3-induced osteoclast differentiation by degrading osteoprotegerin. (2009)
  • Author(s): Yasuhara R, Miyamoto Y, Takami M, Imamura T, Potempa J, Yoshimura K, Kamijo R
  • Journal Title: Biochem J 419 Pages: 159-166
• [Journal Article] 四肢・骨格形成における低分子量Gタンパク質Rac1の役割 (2009)
  • Author(s): 鈴木大,安原理佳,山田篤
  • Journal Title: 口腔組織培養学会誌 18 Pages: 21-27
• [Journal Article] Dose-dependent osteogenic effect of octacalcium phosphate on mouse bone marrow stromal cells. (2008)
  • Author(s): Anada T, Kumagai T, Honda Y, Masuda T, Kamijo R, Kamakura S, Yoshihara N, Kuriyagawa T, Shimauchi H, Suzuki O
  • Journal Title: Tissue Eng Part A 14 Pages: 965-978
• [Journal Article] Toll-like receptor (TLR)による破骨細胞の分化制御 (2008)
  • Author(s): 趙宝紅,高見正道,上條竜太郎
  • Journal Title: 口腔組織培養学会誌 17 Pages: 27-33
• [Presentation] TNF-α Suppresses POEM Expression in Osteoblasts. (2011)
  • Author(s): Tsukasaki M, Yamada A, Miyazono A, Suzuki D, Yoshimura K, Aizawa R, Miyamoto Y, Takami M, Suzawa T, Morimura N, Aruga J, Yamamoto M, Kamijo R
  • Organizer: 89^<th> General Session & Exhibition of the International Associate for Dental Research (IADR)
  • Place of Presentation: San Diego, California, USA.
  • Year and Date: 20110316-20110319
• [Presentation] Carbonic anhydrase IX suppresses hypertrophic differentiation of chondrocytes. (2010)
  • Author(s): Maruyama T, Miyamoto Y, Yamada A, Yamamoto G, Yoshimura K, Akiyama T, Suzawa T, Takami M, Tachikawa T, Baba K, Kamijo R
  • Organizer: The 32nd Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Toronto, Canada.
  • Year and Date: 20101015-20101019
• [Presentation] Alx3, a Paired-type Homeodomein Containing Transcription Factor, Regulates Osteoblast Differentiation Induced by BMP-2. (2010)
  • Author(s): Matsumoto T, Yamada A, Suzuki D, Takami M, Suzawa T, Miyamoto Y, Baba K, Kamijo R
  • Organizer: The 32nd Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Toronto, Canada.
  • Year and Date: 20101015-20101019
• [Presentation] ホメオボックス遺伝子Alx3はBMP-2による骨芽細胞分化を制御する (2010)
  • Author(s): 松本貴志,山田篤,鈴木大,高見正道,須澤徹夫,宮本洋一,馬場一美,上條竜太郎
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20100721-20100723
• [Presentation] Alx3による骨芽細胞分化制御機構の解明 (2010)
  • Author(s): 松本貴志,山田篤,鈴木大,高見正道,須澤徹夫,宮本洋一,馬場一美,上條竜太郎
  • Organizer: 第75回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 北九州
  • Year and Date: 20100625-20100626
• [Presentation] 硬組織構成細胞の分化・増殖制御とそれに基づく硬組織の誘導 (2010)
  • Author(s): 上條竜太郎
  • Organizer: 第10回東京骨軟骨フォーラム プログラム・抄録集
  • Place of Presentation: 東京
  • Year and Date: 2010-07-24
• [Presentation] TGF-βは異所性骨形成を強力に促進する (2010)
  • Author(s): 舘慶太,高見正道,上條竜太郎,馬場一美
  • Organizer: 第9回松本ボーンフォーラム
  • Place of Presentation: 塩尻
  • Year and Date: 2010-05-22
• [Presentation] Alx3はC2C12細胞においてBMP-2による骨芽細胞分化を抑制する (2009)
  • Author(s): 松本貴志,山田篤,鈴木大,高見正道,須澤徹夫,宮本洋一,馬場一美,上條竜太郎
  • Organizer: 第32回日本分子生物学会年会プログラム 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091200
• [Presentation] Novel molecular mechanisms of bone metabolism.-Bone resorption by IRF-8 and bone formation by TGF-β and BMP-2 (2009)
  • Author(s): Kamijo R
  • Organizer: Riken Seminar
  • Place of Presentation: Wako, Japan
  • Year and Date: 20091100
• [Presentation] Essential role of Rac1 during limb development. (2009)
  • Author(s): Suzuki D, Yamada A, Amano T, Yasuhara R, Kimura A, Sakahara M, Tsumaki N, Takeda S, Tamura M, Nakamura M, Shiroishi T, Aiba A, Kamijo R
  • Organizer: American Society for Bone & Mineral Research 31st Annual Meeting Onsite Program American Society for Bone & Mineral Research 31st Annual Meeting
  • Place of Presentation: Denver Colorado, USA
  • Year and Date: 20090900
• [Presentation] Gas6はBMP-2による骨芽細胞分化過程で発現が誘導される (2009)
  • Author(s): 松本貴志,山田篤,鈴木大,高見正道,須澤徹夫,宮本洋一,馬場一美,上條竜太郎
  • Organizer: 第27回日本骨代謝学会学術集会プログラム抄録集 第27回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20090700
• [Presentation] BMP-2 regulates expression of Gas6 during osteoblast differentiation. (2009)
  • Author(s): Matsumoto T, Yamada A, Suzuki D, Takami M, Suzawa T, Miyamoto Y, Baba K, Kamijo R
  • Organizer: Yokosuka Science Festa Program & Proceedings Yokosuka Science Festa 2009
  • Place of Presentation: Yokosuka
  • Year and Date: 20090600
• [Presentation] Role of carbonic anhydrase IX in chondrocyte differentiation. (2009)
  • Author(s): Maruyama T, Miyamoto Y, Yoshimura K, Yamada A, Suzawa T, Takami M, Baba K, Kamijo R
  • Organizer: Yokosuka Science Festa 2009 Program & Proceedings Yokosuka Science Festa 2009
  • Place of Presentation: Yokosuka, Japan
  • Year and Date: 20090600
• [Presentation] BMP-2とヘパリンによる破骨細胞分化促進作用 (2008)
  • Author(s): 舘慶太,高見正道,馬場一美,山田篤,望月文子,井上富雄,上條竜太郎
  • Organizer: 第31回日本分子生物学会年会 第81回日本生化学会大会 合同大会 講演要旨集 第31回日本分子生物学会年会 第81回日本生化学会大会 合同大会 2008年11月
  • Year and Date: 20081100
• [Presentation] Racl controls interdigital programmed cell death in limb buds.Abstracts (2008)
  • Author(s): Suzuki D, Yamada A, Yasuhara R, Tsumaki N, Nakamura M, Kamijo R
  • Organizer: The 1st Showa International Symposium for Life Science 5^<th> Annual Meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20080900
• [Book] Involvement of transcription factor IRF-8 in bone metastasis of cancer (2010)
  • Author(s): Kamijo R, Zhao B, Mochizuki A, Inoue T, Takami M
  • Total Pages: 43-47
  • Publisher: The Waksman Foundation of Japan
• [Book] Transmitters and Modulators in Health and Disease (Shioda S, Homma I, Kato N (Eds.))(Generation of Rac1 conditional mutant mice by Cre/loxP system. New Frontiers in Neuroscience. Tokyo) (2009)
  • Author(s): Suzuki D, Yamada A, Amano T, Kimura A, Yasuhara R, Sakahara M, Tamura M, Tsumaki N, Takeda S, Nakamura M, Shiroishi T, Aiba A, Kamijo R(分担執筆)
  • Total Pages: 175-178
  • Publisher: Springer