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Bone malformations in interleukin-18 transgenic mice.

Yusuke Kawase·Tomoaki Hoshino·Koichi Yokota·Akemi Kuzuhara·Masanori Nakamura·Yu Maeda·Eiji Nishiwaki·Michihisa Zenmyo·Koji Hiraoka·Hisamichi Aizawa·Kohichiro Yoshino
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Abstract

The in vivo effects of IL-18 on bone metabolism were investigated by histopathology in IL-18 transgenic mice. Deformed cortical bone and decreased turnover rate of lumbar trabecular bone are consistent with increased expression of IFN-gamma and IL-18 in the bone marrow. Interleukin (IL)-18 has been demonstrated to inhibit osteoclastogenesis in an in vitro co-culture system. We investigated the effects of IL-18 overexpression on bone metabolism by comparing bone characteristics in male IL-18 transgenic (TG) mice, which secrete mature murine IL-18 from their B- and T-cells, and their wildtype littermates (WT). Histopathological analysis revealed that the cortical bone of the femur was thinner and more deformed in IL-18 TG mice. Bone histomorphometry showed that the cortical bone area of the mid-diaphysis of the femur and the trabecular bone volume of the lumbar vertebrae were significantly reduced in IL-18 TG mice. IL-18 TG mice also exhibited significantly fewer osteoclasts and a reduced bone formation rate in the trabecular bones of their lumbar vertebrae. Real-time reverse transcriptase-polymerase chain reaction amplification of bone marrow cell mRNA revealed that interferon (IFN)-gamma mRNA expression was significantly increased, whereas IL-4 mRNA expression was significantly reduced, in IL-18 TG mice. However, the expression ratio of receptor activator of NFkappaB ligand and osteoprotegerin mRNA was not significantly altered. Thus, deformed cortical bone and a decreased turnover rate of lumbar trabecular bone are characteristic of IL-18 TG mice, and these features might be associated with the increased expression of IFN-gamma and IL-18 in the bone marrow.

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AnimalsB-LymphocytesBase SequenceBone DensityBone and BonesCrosses, GeneticDNA PrimersFemurGlycoproteinsHumansInterferon-gammaInterleukin-18MaleMiceMice, Inbred C57BLMice, TransgenicOsteoclastsOsteoprotegerinRNA, MessengerReceptors, Cytoplasmic and NuclearReceptors, Tumor Necrosis FactorReference ValuesReverse Transcriptase Polymerase Chain ReactionT-LymphocytesTranscription, GeneticJournal ArticleResearch Support, Non-U.S. Gov't

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Yusuke Kawase, Tomoaki Hoshino, Koichi Yokota, Akemi Kuzuhara, Masanori Nakamura, Yu Maeda, Eiji Nishiwaki, Michihisa Zenmyo, Koji Hiraoka, Hisamichi Aizawa, Kohichiro Yoshino. 2003. Bone malformations in interleukin-18 transgenic mice.. https://doi.org/10.1359/jbmr.2003.18.6.975

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