Transgenic mice overexpressing murine thrombopoietin develop myelofibrosis and osteosclerosis

Haruko Kakumitsu, Kenjirou Kamezaki, Kazuya Shimoda, Kennosuke Karube, Takashi Haro, Akihiko Numata, Koutarou Shide, Tadashi Matsuda, Kouichi Oshima, Mine Harada

研究成果: Contribution to journalArticle査読

42 被引用数 (Scopus)

抄録

Thrombopoietin (TPO) regulates megakaryocytopoiesis and platelet production in vivo and in vitro. Exogenous overexpression of TPO in vivo by viral-mediated gene transfer induced bone marrow (BM) fibrosis and osteosclerosis. On the other hand, transgenic mice (Tg) overexpressing TPO using a liver-specific apolipoprotein E (Apo-E) promoter did not exhibit myelofibrosis or osteosclerosis. These discrepancies in phenotype are not fully understood. Then we have investigated the consequences of long-term in vivo overexpression of TPO in a mouse model. Murine TPO Tg mice driven by the IgH promoter were generated. The number of platelets and neutrophils in peripheral blood, and the number of megakaryocytes and granulocytic immature cells in the BM was elevated, together with the number of progenitor cells for megakaryocyte and myeloid cells. TPO Tg mice demonstrated anemia but the number of progenitor cells for the erythrocyte was increased. TPO Tg mice developed myelofibrosis and osteosclerosis as they aged with extramedullary hematopoiesis in the spleen. As plasma transforming growth factors (TGF)-β1 and osteoprotegerin (OPG) levels were higher in TPO Tg mice than in wild-type mice, the development of myelofibrosis and osteosclerosis depends on local TPO levels in BM and might be due to elevated TGF-β1 and OPG.

本文言語英語
ページ(範囲)761-769
ページ数9
ジャーナルLeukemia Research
29
7
DOI
出版ステータス出版済み - 7 2005

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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