title: Teneurin-4, a transmembrane protein, is a novel regulator that suppresses chondrogenic differentiation.
abstract: Teneurin-4 (Ten-4), a transmembrane protein, is expressed in the nervous systems and the mesenchymal tissues, including the cartilage. However, the Ten-4 function in cartilage development remains unknown. Here, we showed that Ten-4 is a novel regulator of chondrogenesis. In situ hybridization analysis revealed that Ten-4 was highly expressed in the mesenchymal condensation area of the mouse femur at embryonic day (E) 13.5, while its expression was decreased in the growth plate of the femur at E18.5. Using the cartilage-like pellet culture of human synovial mesenchymal cells, Ten-4 expression was induced and peaked 7 days after induction of differentiation, while a production of type II and X collagens was increased after Day 14. In the cartilage-like pellet, Ten-4 was highly expressed in the less differentiated region. In the chondrogenic cell line ATDC5, knockdown of Ten-4 expression significantly increased the alcian blue staining and expression levels of aggrecan and type II and X collagens. Further, an elevated expression of Sox6, Sox9, and Runx2 and an attenuation of the ERK activation were observed in the Ten-4-knockdown ATDC5 cells. These results suggested that Ten-4 suppresses chondrogenic differentiation and regulates the expression and activation of the key molecules for chondrogenesis.
authors.affiliation: Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Suzuki
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mizuniwa
authors.forename: Kana
authors.initials: K
authors.lastname: Ishii
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tsuji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muneta
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekiya
authors.forename: Chihiro
authors.initials: C
authors.lastname: Akazawa
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism; D013997:Time Factors
chemical_list: D024043:Collagen Type II; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C493716:Runx2 protein, mouse; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors; C095939:Sox6 protein, mouse; C527933:Sox9 protein, mouse; C576539:TENM4 protein, human; C113761:Tenm4 protein, mouse
keywords: ATDC5; chondrogenic differentiation; human synovial mesenchymal cell; suppressor; teneurin-4