Nitrogen-containing bisphosphonate induces a newly discovered hematopoietic structure in the omentum of an anemic mouse model by stimulating G-CSF production.
We previously reported that the injection of nitrogen-containing bisphosphonate (NBP) induced the site of erythropoiesis to shift from the bone marrow (BM) to the spleen. Our previous study established a severely anemic mouse model that was treated with a combination of NBP with phenylhydrazine (PHZ), which induced newly discovered hematopoietic organs in the omentum. No reports have shown that new hematopoietic organs form under any condition. We characterized the structures and factors related to the formation of these new organs. Splenectomized mice were treated with NBP to inhibit erythropoiesis in the BM and then injected with PHZ to induce hemolytic anemia. The mice showed severe anemia and wine-colored structures appeared in the omentum. Some hematopoietic cells, including megakaryocytes, and well-developed sinuses were observed in these structures. Numerous TER119-positive erythroblasts were located with cells positive for PCNA, a cell proliferation marker. C-kit-positive cells were detected and mRNAs related to hematopoiesis were expressed in these structures. Moreover, TER119-positive erythroblasts emerged and formed clusters and hematopoiesis-related factors were detected in the omentum of mice treated with NBP and PHZ. The levels of G-CSF in the serum and hematopoietic progenitor cells (HPCs) in the peripheral blood were increased upon treatment with both NBP and PHZ. These results suggest that the induced hematopoietic structures act as the sites of erythropoiesis and that NBP-induced G-CSF production causes HPC mobilization, homing and colonization in the omentum because they constitutively express some factors, including SDF-1; thus, the newly discovered hematopoietic structure in this study might be formed.
Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Hirotada
H
Otsuka
Department of Pharmaceutical, Faculty of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanamaru, Otawara-shi, Tochigi, 324-8501, Japan.
Hideki
H
Yagi
Division of Molecular Regulation, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Yasuo
Y
Endo
Department of Veterinary Anatomy, Nippon Veterinary and Animal Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.
Satoshi
S
Soeta
Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Naoko
N
Nonaka
Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. masanaka@dent.showa-u.ac.jp.
Masanori
M
Nakamura
D000740:Anemia / Q000097:blood / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003114:Colony-Forming Units Assay; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000097:blood; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D009584:Nitrogen / Q000494:pharmacology*; D009852:Omentum / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D004164:Diphosphonates; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D009584:Nitrogen
Extramedullary hematopoiesis; G-CSF; Newly discovered hematopoietic structure; Nitrogen-containing bisphosphoanate; SDF-1