title: Mice Deficient in CIZ/NMP4 Develop an Attenuated Form of K/BxN-Serum Induced Arthritis.
abstract: CIZ/NMP4 (Cas interacting zinc finger protein, Nmp4, Zfp384) is a transcription factor that is known to regulate matrix related-proteins. To explore the possible pathophysiological role of CIZ/NMP4 in arthritis, we examined CIZ/NMP4 expression in articular cartilage in arthritis model. CIZ/NMP4 was expressed in the articular chondrocytes of mice at low levels while its expression was enhanced when arthritis was induced. Arthritis induction increased clinical score in wild type mice. In contrast, CIZ/NMP4 deficiency suppressed such rise in the levels of arthritis score and swelling of soft tissue. CIZ/NMP4 deficiency also reduced invasion of inflammatory cells in joint tissue. Quantitative PCR analyses of mRNA from joints revealed that arthritis-induced increase in expressions of IL-1β was suppressed by CIZ/NMP4 deficiency. CIZ/NMP4 bound to IL-1β promoter and activated its transcription. The increase in CIZ/NMP4 in arthritis was also associated with enhancement in bone resorption and cartilage matrix degradation. In fact, RANKL, a signaling molecule prerequisite for osteoclastogenesis and, MMP-3, a clinical marker for arthritis were increased in joints upon arthritis induction. In contrast, CIZ/NMP4 deficiency suppressed the arthritis-induced increase in bone resorption, expression of RANKL and MMP-3 mRNA. Thus, CIZ/NMP4 plays a role in the development of arthritis at least in part through regulation of key molecules related to the arthritis.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamoto
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Izu
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Makiri
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Notomi
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Hayata
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis; D001862:Bone Resorption; D002358:Cartilage, Articular / Q000276:immunology* / Q000473:pathology; D019902:Chondrocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D007106:Immune Sera / Q000008:administration & dosage; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007596:Joints / Q000276:immunology / Q000473:pathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D034521:Nuclear Matrix-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic; D053245:RANK Ligand / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D001323:Autoantibodies; D007106:Immune Sera; D053583:Interleukin-1beta; D034521:Nuclear Matrix-Associated Proteins; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D014157:Transcription Factors; C499081:Zfp384 protein, mouse; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D005956:Glucose-6-Phosphate Isomerase
keywords: ARTHRITIS; OSTEOCALST; TRANSCRIPTION