New Experimental Anemic Model by Using a Nitrogen- Containing Bisphosphonate

Special Article - Anemia

Ann Nutr Disord & Ther. 2017; 4(2): 1043.

New Experimental Anemic Model by Using a Nitrogen- Containing Bisphosphonate

Otsuka H¹, Soeta S², Yagi H³, Endo Y4 and Nakamura M1*

¹Department of Oral Anatomy and Developmental Biology, Showa University, Japan

²Department of Veterinary Anatomy, Nippon Veterinary and Animal Science University, Japan

³Department of Pharmaceutical, International University of Health and Welfare, Japan

4Division of Oral and Maxillofacial Surgery, Tohoku University, Japan

*Corresponding author: Masanaori Nakamura, Department of Oral Anatomy and Developmental Biology, Showa University, School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Received: March 27, 2017; Accepted: May 03, 2017; Published: May 10, 2017


Anemia is a pathological condition associated with various diseases including cancer, and is indicated by a reduction in erythrocyte numbers or the amount of hemoglobin in the peripheral blood. The analysis of changes in hematopoiesis during anemia is important to develop novel therapies and to understand hematopoietic ontogeny. We previously reported that injecting animals with Nitrogen-Containing Bisphosphonate (NBP), which is an inhibitor of osteoclastic bone resorption, decreased erythropoiesis in Bone Marrow (BM). Moreover, we induced severe anemia in a mouse model by injecting NBP in combination with Phenylhydrazine (PHZ), and embryonic type globin mRNA was detected in both the BM and the liver in this anemia model. In addition, wine-colored capsuled structures were unexpectedly observed in the abdominal cavity of this anemic mouse model, and active erythropoiesis was also observed in these structures. Here, we review recent insights into the pathogenic mechanisms underlying various forms of anemia that have been gained through our findings.

Keywords: Nitrogen-containing bisphosphonate; Extramedullary hematopoiesis; Embryonic hemoglobin; GCSF; SDF-1


NBP: Nitrogen-Containing Bisphosphonate; GCSF: Granulocyte-Colony Stimulating Factor; PHZ: Phenylhydrazine; BM: Bone Marrow; SDF-1: Stromal Cell-Derived Factor 1; HSCs: Hematopoietic Stem Cells; HPCs: Hematopoietic Progenitor Cells; EPO: Erythropoietin


Anemia is a pathological condition that involves a reduction in the number of erythrocytes or the amount of hemoglobin in the peripheral blood, and is caused by various diseases such as cancers and bone marrow disorders. The pathology of anemia is very complex, and studies that clarify the mechanism of recovery from anemia and its pathology are essential to establishing an understanding of the therapy, and the ontogeny of hematopoiesis and tissue engineering [1]. Many studies have reported experimental anemia models, including phlebotomy, schistosome parasite infection and draginduction, which are known to be different from the actual disease state (Table 1) [2]. Phenylhydrazine (PHZ) is used to experimentally induce hemolytic anemia in laboratory animals [3], by the mechanism of RBC lipid peroxidation [4,5].