病態生理部門
概要 研究概要
 

 骨は、我々の身体を支えるとともに、生命に重要なカルシウムやリンの貯蔵庫でもあります。この正常な骨の働きを維持するために、生涯を通していろいろな細胞が骨を作り替えています。このとき、骨を造るのが骨芽細胞と呼ばれる筋細胞や脂肪細胞などと近縁の細胞で、骨を壊すのは破骨細胞と呼ばれる血液のマクロファージに由来する細胞です。
 折れた骨が治癒することはよく知られていますが、この再生メカニズムは未だ完全に解明されていません。骨粗鬆症のように骨の量が減ってしまう疾患や、逆に過剰な骨が全身にできてしまうような疾患も知られています。このような骨の疾患に対する新しい治療法や予防法を確立するためにも、骨の細胞群がどのような情報によって調節されているかを解明することが望まれています。病態生理部門では、特に骨芽細胞における分化や機能の調節機構を解析し、骨の形成に重要な信号を分子レベルで明らかにすることを目指しています(図1)。

図1

スタッフ スタッフ
■教 授(部門長)  片桐 岳信
■助 教  大手 聡
■助 手  米山 克美
■研究員  笹沼 寛樹
■ポストドクター  進  正史
■特別研究学生  藤本  舞
テーマ 研究テーマ
 病態生理部門では、主に以下のような研究テーマに取り組んでいます。
1)
 骨誘導因子(BMP)による骨形成メカニズムの解明
2)
 BMP活性調節因子の探索、作用機序の解明および応用
3)
 進行性骨化性線維異形成症(FOP)の発症メカニズムの解明と治療法の確立
(FOPに関する詳しい研究内容や業績は、「埼玉医科大学FOP診療・研究プロジェクト」および「厚労省FOP研究班」のリンク先をご覧下さい。)
文献 主要文献
1)
Fukuda T, Kokabu S, Ohte S, Sasanuma H, Kanomata K, Yoneyama K, Kato H, Akita M, Oda H and Katagiri T. Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3β-dependent but a β-catenin-independent mechanism. Differentiation, in press, (2010).
2)
Nojima J, Kanomata K, Takada Y, Fukuda T, Kokabu S, Ohte S, Takada T, Tsukui T, Yamamoto TS, Sasanuma H, Yoneyama K, Ueno N, Okazaki Y, Kamijo R, Yoda T, and Katagiri T. Dual roles of Smad proteins in the conversion from myoblasts to osteoblastic cells by bone morphogenetic proteins. J Biol Chem, 28: 15577-15586, (2010).
[PMID: 20231279]
3)
Katagiri T. Heterotopic bone formation induced by bone morphogenetic protein signaling: fibrodysplasia ossificans progressiva. J Oral Biosci, 52: 33-41, (2010).
4)
Kokabu S, Nojima J, Kanomata K, Ohte S, Yoda T, Fukuda T and Katagiri T. Protein phosphatase magnesium-dependent 1A-mediated inhibition of BMP signaling is independent of Smad-dephosphorylation. J Bone Miner Res, 25: 653-660, (2010).
[PMID: 19594322]
5)
Yamazaki M, Fukushima H, Shin M, Katagiri T, Takahashi T and Jimi E. TNFα represses BMP signaling by interfering with the DNA binding of Smads through the activation of NF-κB. J Biol Chem, 284: 35987-35995, (2009).
[PMID: 19854828]
6)
Shen Q, Little SC, Xu M, Haupt J, Ast C, Katagiri T, Mundlos S, Seemann P, Kaplan FS, Mullins MC and Shore EM. Fibrodysplasia ossificans progressiva ACVR1 R206H mutation activates ligand-independent and ligand-sensitive chondrogenesis and regulates zebrafish dorso-ventral patterning. J Clin Invest, 19: 3462-3472, (2009).
[PMID: 19855136]
7)
Kanomata K, Kokabu S, Nojima J, Fukuda T and Katagiri T. DRAGON, a GPI-anchored membrane protein, inhibits BMP signaling in C2C12 myoblasts. Genes Cells, 14: 695-702, (2009).
[PMID: 19422419]
8)
Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka-Kanesaki Y, Suda T, Fukuda T, Katagiri T, Kondo Y, Amemiya T, Tashiro H, and Okazaki Y. miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett, 583: 2263-2268, (2009).
[PMID: 19520079]
9)
Fukuda T, Kohda M, Kanomata K, Nojima J, Nakamura A, Kamizono J, Noguchi Y, Iwakiri K, Kondo T, Kurose J, Endo K, Awakura T, Fukushi J, Nakashima Y, Chiyonobu T, Kawara A, Nishida Y, Wada I, Akita M, Komori T, Nakayama K, Nanba A, Maruki Y, Yoda T, Tomoda H, Yu PB, Shore EM, Kaplan FS, Miyazono K, Matsuoka M, Ikebuchi K, Ohtake A, Oda H, Jimi E, Owan I, Okazaki Y, and Katagiri T. Constitutively activated ALK-2 and increased Smad1/5 cooperatively induce BMP signaling in fibrodysplasia ossificans progressiva. J Biol Chem, 284: 7149-7156, (2009).
[PMID: 18684712]
10)
Sato MM, Nashimoto M, Katagiri T, Yawaka Y and Tamura M. Bone morphogenetic protein-2 down-regulates miR-206 expression by blocking its maturation process. Biochem Biophys Res Commun, 383: 125-129, (2009).
[PMID: 19341710]
11)
Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, and Bloch KD. BMP type I receptor inhibition prevents ectopic ossification in a mouse model of fibrodysplasia ossificans progressiva. Nat Med, 14: 1363-1369, (2008).
[PMID: 19029982]
12)
Fukuda T, Kanomata K, Nojima J, Kokabu S, Akita M, Ikebuchi K, Jimi E, Komori T, Maruki Y, Matsuoka M, Miyazono K, Nakayama K, Nanba A, Tomoda H, Okazaki Y, Ohtake A, Oda H, Owan I, Yoda T, Haga N, Furuya H, and Katagiri T. A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor. Biochem Biophys Res Comm, 377: 905-909, (2008).
[PMID: 18952055]
13)
Kaplan F S, Shen Q, Lounev V, Seemann P, Groppe J, Katagiri T, Pignolo R J, and Shore E M. Skeletal Metamorphosis in fibrodysplasia ossificans progressiva (FOP). J Bone Miner Metab, 26: 521-530, (2008).
[PMID: 18979151]
14)
Katagiri T, Suda T, and Miyazono K. The bone morphogenetic proteins. In The TGF-β Family. Miyazono K and Derynck R, editors.Cold Spring Harbor Press, New York, pp121-149, (2008).
15)
Tomoyasu A, Higashio K, Kanomata K, Goto M, Kodaira K, Serizawa H, Suda T, Nakamura A, Nojima J, Fukuda T, and Katagiri T. Platelet-rich plasma stimulates osteoblastic differentiation in the presence of BMPs. Biochem Biophys Res Commun, 361: 62-67, (2007).
[PMID: 17632078]
16)
Fukuda T, Yamagata K, Fujiyama S, Koshida I, Yoshimura K, Fujiki R, Nakamura T, Akimoto C, Yamamoto Y, Katagiri T, Foulds C, Matsumoto T, Kitagawa H, Takeyama K, Takezawa S, O'Malley BW, and Kato S. DEAD-box helicase subunits of the Drosha complex are required for MicroRNA and rRNA processing. Nat Cell Biol 9: 604-611, (2007).
[PMID: 17435748]
17)
Fukuda T, Kanomata K, Nojima J, Urakawa I, Suzawa T, Imada M, Kukita A, Kamijo R, Yamashita T, Katagiri T. FGF23 induces expression of two isoforms of NAB2, which are corepressors of Egr-1. Biochem Biophys Res Commun 353:147-151, (2007).
[PMID: 17174939]
18)
Zhao B, Katagiri T, Toyoda H, Takada T, Yanai T, Fukuda T, Chung U-I, Koike T, Takaoka K, Kamijo R. Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-2. J Biol Chem 281: 23246-23253, (2006).
[PMID: 16754660]
19)
Kodaira K, Imada M, Goto M, Tomoyasu A, Fukuda T, Kamijo R, Suda T, Higashio K, Katagiri T. Purification and identification of a BMP-like factor from bovine serum. Biochem Biophys Res Commun 345: 1224-1231, (2006).
[PMID: 16716261]
20)
Takada T, Katagiri T, Ifuku M, Morimura N, Kobayashi M, Hasegawa K, Ogamo A, Kamijo R. Sulfated polysaccharides enhance the biological activities of bone morphogenetic proteins. J Biol Chem 278: 43229-43235, (2003).
[PMID: 12912996]
21)
Katagiri T, Imada M, Yanai T, Suda T, Takahashi N, Kamijo R. Identification of a BMP-responsive element in Id1, the gene for inhibition of myogenesis. Genes Cells 7: 949-960, (2002).
[PMID: 12296825]
22)
Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 127: 1755-1766, (1994).
[PMID: 7798324]
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