Bone Malformations in Interleukin‐18 Transgenic Mice

• Published in: Journal of bone and mineral research 2003-06, Vol.18 (6), p.975-983
• Main Authors: Kawase, Yusuke, Hoshino, Tomoaki, Yokota, Koichi, Kuzuhara, Akemi, Nakamura, Masanori, Maeda, Yu, Nishiwaki, Eiji, Zenmyo, Michihisa, Hiraoka, Koji, Aizawa, Hisamichi, Yoshino, Kohichiro
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - immunology; Base Sequence; Biological and medical sciences; Bone and Bones - abnormalities; Bone Density; bone histomorphometry; Crosses, Genetic; Diseases of the osteoarticular system; DNA Primers; Femur - pathology; Glycoproteins - genetics; Humans; Interferon-gamma - genetics; Interleukin-18 - genetics; Interleukin-18 - pharmacology; Interleukin-18 - physiology; interleukin‐18; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; osteoclast; Osteoclasts - cytology; Osteoclasts - drug effects; osteodystrophy; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Tumor Necrosis Factor; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; T-Lymphocytes - immunology; Transcription, Genetic; transgenic mouse
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2003.18.6.975

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‐γ 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)‐γ 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 NFκB 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‐γ and IL‐18 in the bone marrow.