{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:29:07Z","timestamp":1787682547098,"version":"build-2784847793"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03b3 and IL-18 in the bone marrow.<\/jats:p>\n               <jats:p>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)-\u03b3 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 NF\u03baB 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-\u03b3 and IL-18 in the bone marrow.<\/jats:p>","DOI":"10.1359\/jbmr.2003.18.6.975","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T23:31:38Z","timestamp":1146094298000},"page":"975-983","source":"Crossref","is-referenced-by-count":36,"title":["Bone Malformations in Interleukin-18 Transgenic Mice"],"prefix":"10.1093","volume":"18","author":[{"given":"Yusuke","family":"Kawase","sequence":"first","affiliation":[{"name":"R&D Laboratories, Nippon Organon K.K., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 1, Kurume University School of Medicine, Kurume, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Yokota","sequence":"additional","affiliation":[{"name":"R&D Laboratories, Nippon Organon K.K., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akemi","family":"Kuzuhara","sequence":"additional","affiliation":[{"name":"R&D Laboratories, Nippon Organon K.K., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Nakamura","sequence":"additional","affiliation":[{"name":"R&D Laboratories, Nippon Organon K.K., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Maeda","sequence":"additional","affiliation":[{"name":"R&D Laboratories, Nippon Organon K.K., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Nishiwaki","sequence":"additional","affiliation":[{"name":"R&D Laboratories, Nippon Organon K.K., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihisa","family":"Zenmyo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Kurume University School of Medicine, Kurume, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Hiraoka","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Kurume University School of Medicine, Kurume, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisamichi","family":"Aizawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 1, Kurume University School of Medicine, Kurume, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohichiro","family":"Yoshino","sequence":"additional","affiliation":[{"name":"R&D Laboratories, Nippon Organon K.K., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019135927200_bib1","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"2024013019135927200_bib2","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1126\/science.289.5484.1501","article-title":"The osteoblast: A sophisticated fibroblast under central surveillance","volume":"289","author":"Ducy","year":"2000","journal-title":"Science"},{"key":"2024013019135927200_bib3","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/378088a0","article-title":"Cloning of a new cytokine that induces IFN-gamma production by T cells","volume":"378","author":"Okamura","year":"1995","journal-title":"Nature"},{"key":"2024013019135927200_bib4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1006\/meth.1999.0837","article-title":"Interleukin-18","volume":"19","author":"Dinarello","year":"1999","journal-title":"Methods"},{"key":"2024013019135927200_bib5","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1146\/annurev.immunol.19.1.423","article-title":"Interleukin-18 regulates both th1 and th2 responses","volume":"19","author":"Nakanishi","year":"2001","journal-title":"Annu Rev Immunol"},{"key":"2024013019135927200_bib6","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.4049\/jimmunol.162.2.1096","article-title":"IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses","volume":"162","author":"Olee","year":"1999","journal-title":"J Immunol"},{"key":"2024013019135927200_bib7","doi-asserted-by":"crossref","first-page":"5041","DOI":"10.4049\/jimmunol.162.9.5041","article-title":"Cutting edge: Generation of IL-18 receptor-deficient mice. 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