title: Identification of SCAN domain zinc-finger gene ZNF449 as a novel factor of chondrogenesis.
abstract: Transcription factors SOX9, SOX5 and SOX6 are indispensable for generation and differentiation of chondrocytes. However, molecular mechanisms to induce the SOX genes are poorly understood. To address this issue, we previously determined the human embryonic enhancer of SOX6 by 5'RACE analysis, and identified the 46-bp core enhancer region (CES6). We initially performed yeast one-hybrid assay for screening other chondrogenic factors using CES6 as bait, and identified a zinc finger protein ZNF449. ZNF449 and Zfp449, a counterpart in mouse, transactivated enhancers or promoters of SOX6, SOX9 and COL2A1. Zfp449 was expressed in mesenchyme-derived tissues including cartilage, calvaria, muscle and tendon, as well as in other tissues including brain, lung and kidney. In limb cartilage of mouse embryo, Zfp449 protein was abundantly located in periarticular chondrocytes, and decreased in accordance with the differentiation. Zfp449 protein was also detected in articular cartilage of an adult mouse. During chondrogenic differentiation of human mesenchymal stem cells, ZNF449 was increased at an early stage, and its overexpression enhanced SOX9 and SOX6 only at the initial stage of the differentiation. We further generated Zfp449 knockout mice to examine the in vivo roles; however, no obvious abnormality was observed in skeletal development or articular cartilage homeostasis. ZNF449 may regulate chondrogenic differentiation from mesenchymal progenitor cells, although the underlying mechanisms are still unknown.
authors.affiliation: Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Okada
authors.affiliation: Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Sports Medicine and Orthopedics, Kanto Rosai Hospital, Japan Labour Health and Welfare Organization, Kanagawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukai
authors.affiliation: Bone and Cartilage Regenerative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.affiliation: Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Orthopedic Surgery, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hosaka
authors.affiliation: Bone and Cartilage Regenerative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Yano
authors.affiliation: Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Ung-il
authors.initials: UI
authors.lastname: Chung
authors.affiliation: Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Spine Center, Tokyo Shinjuku Medical Center, Japan Community Health care Organization, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Division of Transfusion Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Bone and Cartilage Regenerative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D017434:Protein Structure, Tertiary; D055747:SOX Transcription Factors / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D055747:SOX Transcription Factors; C515712:ZNF449 protein, human