2002 Fiscal Year Annual Research Report

骨髄内及び骨髄外B細胞造血機構の解析

Research Project

Project/Area Number	13670318
Research Institution	Tottori University
Principal Investigator	林眞一鳥取大学, 医学部, 教授 (50208617)
Keywords	骨髄 / B細胞 / 骨大理石病 / 髄外造血 / ストロマ細胞 / マウス / 破骨細胞 / 骨芽細胞
Research Abstract	骨髄腔形成不全の3種の原因の異なる破骨細胞欠損大理石病マウスを用いて、狭小化した骨髄内ではB細胞系譜の造血のみが特異的に欠落していることを見いだした。系統発生学的にも骨髄形成不全と骨髄内B細胞造血欠損には相関が見られることから、破骨細胞とB細胞造血の関連について検討した。以下にその結果を示す。 1)骨髄内造血におけるWnt-3aの効果について検討した。Wnt-3aはB細胞分化を亢進するという従来報告されていた結果とは異なり、造血支持細胞を介して初期B細胞分化には抑制的に作用すること、一方、破骨細胞系譜には影響を及ぼさないことを明らかにした。 2)B細胞分化に抑制的に作用するとされるNotchシグナルの効果をリガンドのDelta-1を用いて検討した。Notchシグナルは破骨細胞前駆細胞に直接作用し、かつ、支持細胞のマクロファージコロニー刺激因子の発現を抑制し、破骨細胞分化抑制因子の発現を亢進させることで破骨細胞分化に抑制的に作用することを明らかにした。 3)破骨細胞前駆細胞へのToll-like受容体(TLR)からのシグナルの効果を検討し、骨髄内と骨髄外に存在する破骨細胞の前駆細胞ではTLRからのシグナルへの反応性が異なり、骨髄外の前駆細胞の成熟は抑制されることを明らかにした(投稿中)。 4)ES細胞一個からの骨髄形成モデルを作成し、骨芽細胞、破骨細胞、血管内皮細胞をコロニー内に誘導し、その構築について検討した。 1)2)4)はすでに論文発表済み、3)は投稿中である。我々の研究(Blood95:3363,2000)が引き金になり、最近、大理石病マウスのB細胞造血機構の研究が盛んになり候補遺伝子についてもいくつか報告がなされ始めてきた。ようやく造血機構を明らかにする手法を見いだしたと確信している。今後、制御分子解明に邁進するつもりである。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Yamane, T., et al.: "Wnt signaling regulates hemopoiesis through stromal cells"J. Immunol.. 167. 765-772 (2001)
[Publications] Okuyama, H., et al.: "Development of osteoclast lineage cells"Research Advances in Blood. 1. 75-84 (2001)
[Publications] Kunisada, T., et al.: "Ligands for receptor tyrosine kinases expressed in the skin as environmental factors for melanocyte development"J. Invest. Dermatol. Symp. Proc.. 6. 6-9 (2001)
[Publications] Hemmi, H., et al.: "Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-β1-dependent cells"Int. Immunol.. 13. 695-704 (2001)
[Publications] Makiishi-Shimobayashi, C.: "Interleukin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells"B. B. R. C. 281. 361-366 (2001)
[Publications] Hemmi, H., et al.: "Temporal and spatial localization of osteoclasts in colonies from embryonic stem cells"B. B. R. C. 280. 526-534 (2001)
[Publications] Yamazaki, H., et al.: "Presence of osteoclast precursors in the colonies cloned in the presence of hematopoietic colony-stimulating factors"Exp. Hematol.. 29. 68-76 (2001)
[Publications] Hayashi, S.I., et al.: "In vitro induction of differentiation from embryonic stem cells : looking forward to regenerative medicine"Nihon Hansenbyo Gakkai Zassi. 70. 121-126 (2001)
[Publications] Yamada, N., et al.: "Interleukin-18 and interkeukin-12 synergistically inhibit osteoclastic bone -resorbing activity"Bone. 30. 901-908 (2002)
[Publications] Christianson, S.W., et al.: "T cell developmental defects in viable motheaten mice deficient in SHP-1 protein-tyrosine phosphatase. Developmental defects are corrected in vitro in the presence of normal hematopoietic-origin stromal cells and in vivo by exo"J. Autoimmunity. 18. 119-130 (2002)
[Publications] Nagai, Y., et al.: "Requirement for MD-1 in cell surface expression of RP105/CD18O and B cell responsiveness to lipopolysaccharide"Blood. 99. 1699-1705 (2002)
[Publications] Yoshino, M., et al.: "Reduction of osteoclasts in the critical embryonic period is essential for inhibition of mouse tooth eruption"J. Bone Miner. Res.. 18. 108-116 (2003)
[Publications] Yamada, T., et al.: "Regulation of osteocilast development by Notch signaling directed to osteoclast precursors and through stromal cells"Blood. 101. 2227-2234 (2003)
[Publications] Yamane, T., et al.: "Embryonic stem cells as a model to study melanocyte lineage"In Embryonic Stem Cells : Methods and Protocols. (Methods in Molecular Biology) Ed. K.Turksen. The Humana Press Inc.,. 185. 261-268 (2002)
[Publications] Yamane, T., et al.: "Embryonic stem cells as a model to study osteoclast lineage"In Embryonic Stem Cells : Methods and Protocols. (Methods in Molecular Biology) Ed. K.Turksen. The Humana Press Inc.,. 185. 97-106 (2002)
[Publications] Tsuneto, M., et al.: "In vitro differentiation of mouse ES cells into hematopoietic, endothelial, and osteoblastic cell lineages : A possibility of in vitro organogenesis"In Differentiation of Embryonic Stem Cells, Eds. P.M.Wassarman, and G.M.Keller, Academic Press, San Diego, CA, Methods in Enzymology. (in press).

2002 Fiscal Year Annual Research Report

骨髄内及び骨髄外B細胞造血機構の解析

Principal Investigator

林 眞一 鳥取大学, 医学部, 教授 (50208617)

Research Products

[Publications] Yamane, T., et al.: "Wnt signaling regulates hemopoiesis through stromal cells"J. Immunol.. 167. 765-772 (2001)

[Publications] Okuyama, H., et al.: "Development of osteoclast lineage cells"Research Advances in Blood. 1. 75-84 (2001)

[Publications] Kunisada, T., et al.: "Ligands for receptor tyrosine kinases expressed in the skin as environmental factors for melanocyte development"J. Invest. Dermatol. Symp. Proc.. 6. 6-9 (2001)

[Publications] Hemmi, H., et al.: "Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-β1-dependent cells"Int. Immunol.. 13. 695-704 (2001)

[Publications] Makiishi-Shimobayashi, C.: "Interleukin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells"B. B. R. C. 281. 361-366 (2001)

[Publications] Hemmi, H., et al.: "Temporal and spatial localization of osteoclasts in colonies from embryonic stem cells"B. B. R. C. 280. 526-534 (2001)

[Publications] Yamazaki, H., et al.: "Presence of osteoclast precursors in the colonies cloned in the presence of hematopoietic colony-stimulating factors"Exp. Hematol.. 29. 68-76 (2001)

[Publications] Hayashi, S.I., et al.: "In vitro induction of differentiation from embryonic stem cells : looking forward to regenerative medicine"Nihon Hansenbyo Gakkai Zassi. 70. 121-126 (2001)

[Publications] Yamada, N., et al.: "Interleukin-18 and interkeukin-12 synergistically inhibit osteoclastic bone -resorbing activity"Bone. 30. 901-908 (2002)

[Publications] Nagai, Y., et al.: "Requirement for MD-1 in cell surface expression of RP105/CD18O and B cell responsiveness to lipopolysaccharide"Blood. 99. 1699-1705 (2002)

[Publications] Yoshino, M., et al.: "Reduction of osteoclasts in the critical embryonic period is essential for inhibition of mouse tooth eruption"J. Bone Miner. Res.. 18. 108-116 (2003)

[Publications] Yamada, T., et al.: "Regulation of osteocilast development by Notch signaling directed to osteoclast precursors and through stromal cells"Blood. 101. 2227-2234 (2003)

[Publications] Yamane, T., et al.: "Embryonic stem cells as a model to study melanocyte lineage"In Embryonic Stem Cells : Methods and Protocols. (Methods in Molecular Biology) Ed. K.Turksen. The Humana Press Inc.,. 185. 261-268 (2002)

[Publications] Yamane, T., et al.: "Embryonic stem cells as a model to study osteoclast lineage"In Embryonic Stem Cells : Methods and Protocols. (Methods in Molecular Biology) Ed. K.Turksen. The Humana Press Inc.,. 185. 97-106 (2002)

林眞一鳥取大学, 医学部, 教授 (50208617)