Prevention of Senile Osteoporosis in SAMP6 Mice by Intrabone Marrow Injection of Allogeneic Bone Marrow Cells

Authors

  • Naoya Ichioka,

    1. First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan
    2. Department of Orthopedic Surgery, Kansai Medical University, Moriguchi City, Osaka, Japan
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  • Muneo Inaba,

    1. First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan
    2. Transplantation Center, Kansai Medical University, Moriguchi City, Osaka, Japan
    3. Regeneration Research Center for Intractable Diseases, Kansai Medical University, Moriguchi City, Osaka, Japan
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  • Taketohi Kushida,

    1. First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan
    2. Department of Orthopedic Surgery, Kansai Medical University, Moriguchi City, Osaka, Japan
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  • Takashi Esumi,

    1. First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan
    2. Department of Orthopedic Surgery, Kansai Medical University, Moriguchi City, Osaka, Japan
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  • Kazuhiko Takahara,

    1. Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
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  • Kayo Inaba,

    1. Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
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  • Ryokei Ogawa,

    1. Department of Orthopedic Surgery, Kansai Medical University, Moriguchi City, Osaka, Japan
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  • Hirokazu Iida,

    1. Department of Orthopedic Surgery, Kansai Medical University, Moriguchi City, Osaka, Japan
    2. Transplantation Center, Kansai Medical University, Moriguchi City, Osaka, Japan
    3. Regeneration Research Center for Intractable Diseases, Kansai Medical University, Moriguchi City, Osaka, Japan
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  • Susumu Ikehara M.D., Ph.D.

    Corresponding author
    1. First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan
    2. Department of Orthopedic Surgery, Kansai Medical University, Moriguchi City, Osaka, Japan
    3. Regeneration Research Center for Intractable Diseases, Kansai Medical University, Moriguchi City, Osaka, Japan
    • First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan. Telephone: 81-6-6993-9429; Fax: 81-6-6994-8283
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Abstract

The SAMP6 mouse (a substrain of senescence-accelerated mice) spontaneously develops osteoporosis early in life and is, therefore, a useful model for examining the mechanisms underlying osteoporosis. We have recently established a new bone marrow transplantation (BMT) method: the bone marrow cells (BMCs) of normal allogeneic mice are directly injected into the bone marrow (BM) cavity of irradiated (5.5 Gy × 2) recipients (IBM-BMT). Using IBM-BMT, we attempted to prevent osteoporosis in SAMP6 mice. The hematolymphoid system was completely reconstituted with donor-type cells after IBM-BMT. Thus-treated SAMP6 mice showed marked increases in trabecular bones even at 12 months of age, and the bone mineral density remained similar to that of normal B6 mice. In concordance with these findings, urinary deoxypyridinoline also remained continuously low until 10 months of age, indicating that IBM-BMT was effective in the prevention of bone absorption.

In addition to the above, BM stromal cells in the treated SAMP6 mice were replaced with donor stromal cells, and the message level of interleukin-11 (IL-11), which is produced by the BM stromal cells and is known as an important factor in the regulation of bone remodeling, was restored to a level similar to that observed in normal B6 mice. Furthermore, the message level of IL-6, which is known to enhance osteoclastogenesis, was also restored to normal. These results indicate that the BM microenvironment was normalized after IBM-BMT and that the increased production of IL-11 and IL-6 ameliorated the imbalance between bone absorption and formation, resulting in the prevention of osteoporosis in SAMP6 mice.

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