title: Double-stranded RNA-dependent protein kinase regulates insulin-stimulated chondrogenesis in mouse clonal chondrogenic cells, ATDC-5.
abstract: Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein that has been identified and characterized as a translational inhibitor in an interferon-regulated antiviral pathway. PKR is also reported to play important roles in the regulation of cell growth and differentiation. We have previously demonstrated that PKR inactivation suppresses osteoblast calcification and osteoclast formation. However, reports concerning the roles of PKR in chondrogenesis are limited. In this study, we have demonstrated that PKR is required for the in vitro differentiation of the mouse clonal chondrogenic cell line ATDC-5. ATDC-5 cells treated with insulin differentiated into chondrocytes and produced an alcian-blue-positive cartilage matrix. The protein expression of signal transducers and activators of transcription (STAT) peaked at day 7 of differentiation, whereas the expression of SRY-box-containing gene 9 (Sox-9), which is a transcription factor for chondrocyte differentiation, increased gradually. When the cells were treated with a PKR inhibitor (2-aminopurine), the cartilage matrix formation decreased. The protein expression of STAT1 continued to increase up to day 21, whereas the expression of Sox-9 was low and did not increase. We also demonstrated that PKR was localized to a marginal region of the mandibular condyle cartilage in mouse embryos. Our findings suggest that PKR has important functions in the differentiation of chondrocytes through the modulation of STAT1 and Sox-9 expression.
authors.affiliation: Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka, Japan. morimoto@med.uoeh-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morimoto
authors.forename: Ryoko
authors.initials: R
authors.lastname: Baba
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Haneji
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Doi
mesh_terms: D015075:2-Aminopurine / Q000494:pharmacology; D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D020219:Chondrogenesis / Q000187:drug effects*; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008335:Mandibular Condyle / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D051379:Mice; D008813:Mice, Inbred ICR; D055758:SOX9 Transcription Factor / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D024043:Collagen Type II; D007328:Insulin; D055758:SOX9 Transcription Factor; D050794:STAT1 Transcription Factor; D015075:2-Aminopurine; D019892:eIF-2 Kinase