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 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-kappaB 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.
Ueda
Yusuke
Y
First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.
Inaba
Muneo
M
Takada
Keizo
K
Fukui
Junichi
J
Sakaguchi
Yutaku
Y
Tsuda
Masanobu
M
Omae
Mariko
M
Kushida
Taketoshi
T
Iida
Hirokazu
H
Ikehara
Susumu
S
D000596:Amino Acids / Q000652:urine; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D015519:Bone Density; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D017148:Infusions, Intraosseous; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D000596:Amino Acids; D000954:Antigens, Surface; D016207:Cytokines; C036020:deoxypyridinoline