Transgenic mice overexpressing soluble osteoclast differentiation factor (sODF) exhibit severe osteoporosis (original) (raw)

Abstract.

Osteoclast differentiation factor, ODF, also called RANKL, TRANCE, or OPGL, is a key molecule for osteoclast differentiation and activation, and is thought to act as a membrane-associated molecule in bone remodeling. Recent study suggested that soluble ODF (sODF) released from T cells also has some roles in bone resorption. To investigate the physiological and pathological function of sODF, we generated two types of transgenic mice overexpressing sODF. Mice overexpressing sODF ubiquitously from the early developmental stage died at the late fetal stage. The other type of mice, expressing sODF only in the liver after birth, grew to maturity with normal body size and weight. However, they exhibited a marked decrease in bone mineral density with aging compared with their non-transgenic littermates, and in addition, the strength of their femurs was extremely reduced. Histological analysis showed that the trabecular bone mass was decreased at 6 weeks of age and was sparse at age 3–4 months. The number of osteoclasts was significantly increased, while the number of osteoblasts was not altered on the surface of young trabecular bone. These results indicate that excessive production of sODF causes osteoporosis by accelerated osteoclastogenesis. The transgenic mouse overexpressing sODF in the liver could serve as a useful animal model for studying bone remodeling and evaluating therapeutic agents for osteoporosis.

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Authors and Affiliations

  1. Research Institute of Life Science, Snow Brand Milk Products, Co., Ltd., Tochigi, Japan, , , , , , JP
    Atsuko Mizuno, Takeshi Kanno, Masaki Hoshi, Osamu Shibata, Kazuki Yano, Nobuaki Fujise, Masahiko Kinosaki, Kyoji Yamaguchi, Eisuke Tsuda, Akihiko Murakami, Hisataka Yasuda & Kanji Higashio

Authors

  1. Atsuko Mizuno
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  2. Takeshi Kanno
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  3. Masaki Hoshi
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  4. Osamu Shibata
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  5. Kazuki Yano
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  6. Nobuaki Fujise
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  7. Masahiko Kinosaki
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  8. Kyoji Yamaguchi
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  9. Eisuke Tsuda
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  10. Akihiko Murakami
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  11. Hisataka Yasuda
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  12. Kanji Higashio
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Additional information

Received: March 7, 2002 / Accepted: May 10, 2002

Acknowledgments. The authors wish to thank Dr. Junichi Miyazaki (Osaka University) for the gift of pCAGGS and pSG2 plasmid vectors. We thank Dr. Yasushi Sato for histological evaluation, Ms. Chiharu Ogiwara for bone analysis, and Ms. Toshie Tomizuka for biochemical analysis of serum. We thank Dr. Kazuhiro Aoki and Dr. Keiichi Ohya (Tokyo Medical and Dental University) for helpful discussions. We also thank Dr. Makoto Suzuki (Jichi Medical School) for helpful suggestions and critical review of this manuscript.

Offprint requests to: H. Yasuda

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Mizuno, A., Kanno, T., Hoshi, M. et al. Transgenic mice overexpressing soluble osteoclast differentiation factor (sODF) exhibit severe osteoporosis.J Bone Miner Metab 20, 337–344 (2002). https://doi.org/10.1007/s007740200049

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