title: TGF-β Suppresses Ift88 Expression in Chondrocytic ATDC5 Cells.
abstract: Ift88 is an intraflagella transport protein, critical for the cilium, and has been shown to be required for the maintenance of chondrocytes and cartilage. However, how Ift88 is controlled by cytokines that play a role in osteoarthritis is not well understood. Therefore, we examined the effects of TGF-β on the expression of Ift88. We used ATDC5 cells as chondrocytes and analyzed the effects of TGF-β on gene expression. TGF-β treatment suppresses the levels of Ift88 mRNA in a dose-dependent manner starting from as low as 0.5 ng/mL and reaching the nadir at around 2 ng/mL. TGF-β treatment also suppresses the protein levels of Ift88. TGF-β suppression of Ift88 is still observed when the cells are cultured in the presence of a transcriptional inhibitor while the TGF-β suppression is weakened in the presence of a protein synthesis inhibitor, cycloheximide. TGF-β treatment suppresses the levels of Ift88 mRNA stability suggesting the presence of posttranscriptional regulation. TGF-β treatment reduces the number of cilia positive cells and suppresses average length of cilia. Knockdown of Ift88 by siRNA enhances TGF-β-induced increase in type II collagen mRNA expression in ATDC5 cells revealing the suppressive role of Ift88 on TGF-β-induced regulation of extracellular matrix protein expression. TGF-β also suppresses Ift88 mRNA expression in primary culture of rib chondrocytes. These data indicate that TGF-β regulates Ift88 gene expression at least in part via posttrascriptional manner.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 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, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 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, 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, 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, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D002923:Cilia / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: C490898:Tg737Rpw protein, mouse; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins