Induction of Senile Osteoporosis in Normal Mice by Intra‐Bone Marrow‐Bone Marrow Transplantation from Osteoporosis‐Prone Mice

A P6 substrain of the senescence accelerated mouse (SAMP6) spontaneously develops osteoporosis early in life. These mice show the clinical signs of osteoporosis, such as elevated levels of urinary deoxypyridinoline (Dpd), decreased bone mineral density (BMD), and a significant loss of trabecular and...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2007-06, Vol.25 (6), p.1356-1363
Main Authors: Ueda, Yusuke, Inaba, Muneo, Takada, Keizo, Fukui, Junichi, Sakaguchi, Yutaku, Tsuda, Masanobu, Omae, Mariko, Kushida, Taketoshi, Iida, Hirokazu, Ikehara, Susumu
Format: Article
Language:English
Subjects:
Amino Acids - urine
Animals
Antigens, Surface - analysis
Bone Density
Bone Marrow Transplantation
Cells, Cultured
Cytokines - analysis
Disease Models, Animal
Female
Infusions, Intraosseous
Intra‐bone marrow injection
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Osteoporosis - etiology
Osteoporosis - immunology
Osteoporosis - metabolism
Osteoporosis - pathology
Senile osteoporosis Senescence accelerated mouse P6
Stem cell disorder
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Summary:A P6 substrain of the senescence accelerated mouse (SAMP6) spontaneously develops osteoporosis early in life. These mice show the clinical signs of osteoporosis, such as elevated levels of urinary deoxypyridinoline (Dpd), decreased bone mineral density (BMD), and a significant loss of trabecular and cortical bone thickness at 12 months of age. Here, we describe the transfer of osteoporosis to a normal strain by the injection of bone marrow cells from SAMP6 donors directly into the bone marrow cavity (intra‐bone marrow‐bone marrow transplantation [IBM‐BMT]). More than 1 month after IBM‐BMT, hematolymphoid cells were completely reconstituted by donor‐derived cells, and bone marrow stromal cells that could differentiate into osteocytes were also found to be of donor origin. In addition, the recipient C57BL/6 mouse showed the features of osteoporosis in the trabecular bone. Decreases in BMD and increases in urinary Dpd were also observed. When the message levels of cytokines (interleukin [IL]‐11, IL‐6, receptor activator of NF‐κB ligand [RANKL], osteoprotegerin, macrophage–colony‐stimulating factor, and insulin‐like growth factor‐1) were examined by reverse transcription‐polymerase chain reaction (RT‐PCR) and real‐time RT‐PCR analysis, IL‐6 and IL‐11 were reduced to a level similar to that in SAMP6 mice, whereas that of RANKL was increased. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment are reconstituted as a result of IBM‐BMT, and suggest that the development of senile osteoporosis might be attributable to “stem cell disorders.” Disclosure of potential conflicts of interest is found at the end of this article.
ISSN:1066-5099
1549-4918
DOI:10.1634/stemcells.2006-0811