title: Bone morphogenetic protein-2 enhances osterix gene expression in chondrocytes.
abstract: Osterix is a recently identified zinc-finger-containing transcription factor, which is required for skeletogenesis as no bone formation was observed in osterix-deficient mice. Osterix was first cloned as a gene whose expression was enhanced by BMP in C2C12 cells. As BMP induces ectopic bone formation in vivo via a pathway reminiscent to endochondral bone formation, BMP may also regulate osterix gene expression in chondrocytes. However, no information was available regarding the BMP actions on osterix gene expression in chondrocytes. We therefore examined the effects of BMP-2 on osterix gene expression in chondrocytes in culture. RT-PCR analysis indicated that osterix mRNA was expressed in the primary cultures of chondrocytes derived from mouse rib cartilage. The treatment with BMP-2 enhanced the levels of osterix transcripts within 24 h and the enhancement was still observed at 48 h based on RT-PCR analysis. This BMP effect was specific to this cytokine, as TGF-beta did not alter osterix gene expression. BMP effects on the osterix mRNA levels were also confirmed by Northern blot analysis. The enhancing effect of BMP on osterix gene expression was observed in a dose-dependent manner starting at 200 ng/ml. The BMP enhancement of the osterix gene expression in chondrocytes was blocked in the presence of a protein synthesis inhibitor, cycloheximide, while it was still observed in the presence of 5,6-dichloro-1-beta D-ribofuranosylbenzimidazol (DRB) suggesting the involvement of post-transcriptional events, which require new protein synthesis. These results indicated that osterix gene is expressed in the primary cultures of chondrocytes and its expression is under the control of BMP-2.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yagi
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
authors.forename: A
authors.initials: A
authors.lastname: Nifuji
authors.forename: K
authors.initials: K
authors.lastname: Shinomiya
authors.forename: K
authors.initials: K
authors.lastname: Nakashima
authors.forename: B
authors.initials: B
authors.lastname: DeCrombrugghe
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D003513:Cycloheximide; D004004:Dichlororibofuranosylbenzimidazole; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors; D011499:Protein Processing, Post-Translational; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger / Q000032:analysis; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta; D015854:Up-Regulation
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D004004:Dichlororibofuranosylbenzimidazole; D003513:Cycloheximide