2004 Fiscal Year Final Research Report Summary
Bone Marrow Microenvironments for Hematopoiesis
| Project/Area Number |
15590344
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National University Corporation Tottori University |
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Principal Investigator |
HAYASHI Shin-ichi Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (50208617)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Bone marrow / Hematopoiesis / Osteoclast / B cell / Toll-like receptor / Lipopolysaccharide(LPS) / Tyrosine phosphatase / Embryonic stem(ES) cell |
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| Research Abstract |
1)Analysis of osteoclastogenesis for bone marrow formation :
Osteoclasts are hematopoietic cells, which participate in bone resorption and remodeling. Receptor activator of NF-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) are critical for development of osteoclasts. The Toll-like receptor(TLR) family shares some of the downstream signaling with RANK, however, the signaling via TLRs has never been reported to induce osteoclastogenesis without RANKL. We showed that significant numbers of mature osteoclasts were generated from protein tyrosine phosphatase SHP-1-defective me^v/me^v bone marrow cells in the presence of M-CSF and LPS, a TLR4 ligand without addition of RANKL in culture. The osteoclast precursors were present in the Kit-positive cell enriched fraction of BM cells. Although me^v/me^v bone marrow cells required a comparable concentration of RANKL or TNF-α as wild-type cells for the initiation of osteoclastogenesis, numbers of multinucleated osteoclasts in me^v/
… More
me^v bone marrow cultures were significantly increased by the equivalent dose of RANKL or TNF-α in the presence of M-CSF. These results indicate that a defect of SHP-1 function not only accelerates physiological osteoclast development by RANKL/RANK, but also acquires an aberrant pathway for osteoclastogenesis by LPS.
2)Induction of hematopoiesis from blood-less embryonic stem (ES) cell line :
Transcription factor Tal-1 is essential for the specification of hematopoietic development. Mice lacking Tall fail to generate any hematopoietic precursors. Using our co-culture system with stromal cells, we demonstrate that enforced expression of the transcription factor PU.1 under tetracycline control in Tall-null ES cells rescues the development of osteoclasts and macrophage-like phagocytes expressing a macrophage restricted marker. Other hematopoietic lineage cells were not generated. Their development was dependent on M-CSF and RANKL. These results suggest that the expression of PU.1 is a critical event for osteoclastogenesis and that Tal-1 may lie upstream of PU.1 in a regulatory hierarchy during osteoclastogenesis. Less
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Research Products
(30 results)
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[Journal Article] Enforced expression of PU.1 rescues osteoclastogenesis from embryonic stem cells lacking Tal-1.2005
Author(s)
Tsuneto, M., Tominaga, A., Yamazaki, H., Yoshino, M., Orkin, S.H., Hayashi, S.I.
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Journal Title
Stem Cells 23
Pages: 134-143
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lipopolysaccharide-induced osteoclastogenesis in Src homology 2-domain phosphatase-1-deficient viable motheaten mice.2004
Author(s)
Hayashi.S.I., Tsuneto, M., Yamada, T., Nose, M., Yoshino, M., Shultz, L.D., Yamazaki, H.
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Journal Title
Endocrinology 145
Pages: 2721-2729
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Osteoclast Lineage (Chapter 27).2004
Author(s)
Yamane, T., Okuyama, H., Tsuneto, M., Hemmi, H., Yamazaki, H., Hayashi.S.I.
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Journal Title
Handbook of Stem Cells (Eds.R.P.Lanza, et al.)(Academic Press, San Diego, CA.)Embryonic Stem Cells Vol.1
Pages: 295-303
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through atromal cells.2003
Author(s)
Yamada, T., Yamazaki, H., Yamane, T., Yoshino, M., Okuyama, H., Tsuneto, M., Kurino, T, Hayashi, S.I., Sakano, S.
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Journal Title
Blood 101
Pages: 2227-2234
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Reduction of osteoclasts in the critical embryonic period is essential for inhibition of mouse tooth eruption.2003
Author(s)
Yoshino, M., Yamazaki, H., Yoshida, H., Niida, S., Nishikawa, S.I., Ryoke, K., Kunisada, T., Hayashi, S.I.
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Journal Title
J.Bone Miner.Res. 18
Pages: 108-116
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells.2003
Author(s)
Hirano, M., Yamamoto, A., Yoshimura, N., Tokunaga, T., Motohashi, T., Ishizaki, K., Yoshida, H., Okazaki, K, Yamazaki, H., Hayashi, S.I., Kunisada, T.
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Journal Title
Dev.Dyn. 228
Pages: 664-671
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-like receptor ligands and TNF-α2003
Author(s)
Hayashi.S.I., Yamada, T., Tsuneto, M., Yamane, T., Takahashi, M., Shultz, L.D., Yamazaki H.
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Journal Title
J.Immunol. 171
Pages: 5130-5139
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Distinct antigen trafficking from skin in the steady and active states.2003
Author(s)
Yoshino, M., Yamazaki, H., Nakano, H., Kakiuchi, T., Ryoke, K., Kunisada, T., Hayashi, S.I.
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Journal Title
Int.Immunol. 15
Pages: 773-779
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] In vitro differentiation of mouse ES cells into hematopoietic, endothelial, and osteoblastic cell lineages : A possibility of in vitro organogenesis.2003
Author(s)
Tsuneto, M., Yamane, T., Okuyama, H., Yamazaki, H., Hayashi, S.I.
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Journal Title
Differentiation of Embryonic Stem Cells (Eds.P.M.Wassarman, and G.M.Keller)(Academic Press, San Diego, CA) Methods Enzymol. 365
Pages: 98-114
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Tooth development and tooth regeneration using tooth germ, dental pulp cells, neural crest cells and embryonic stem cells.2003
Author(s)
Yamazaki, H., Kurino, T., Sakata, E., Yoshino, M., Hayashi.S.I.
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Journal Title
Recent Research Development in Biophysics and Biochemistry (Research Signpost) 3
Pages: 907-925
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Presence and distribution of neural crest-derived cells in the murine developing thymus and their potential for differentiation.
Author(s)
Yamazaki, H., Sakata, E., Yamane, T., Yanagisawa, A., Abe, K., Yamamura, K.I., Hayashi, S.I., Kunisada, T.
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Journal Title
Description
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