The bone morphogenetic protein antagonist Noggin is regulated by Sox9 during endochondral differentiation.
Noggin has been described to be capable of binding bone morphogenetic proteins (BMP) and inhibiting BMP signaling by preventing the interactions of BMP with their receptors. Noggin expression during endochondral differentiation was analyzed to elucidate its potential role during chondrogenesis. Throughout mouse development, Noggin was expressed abundantly in the chondrocytic lineage as early as collagen type II RNA was detectable. In addition, a strong correlation was detected between Noggin expression and the expression profile of Sox9 during chondrogenesis. Sox9 (known to play an important role during chondrogenesis) and Noggin expression were investigated in the pluripotent mesenchymal cell line C3H10T1/2, stimulated by BMP-2. BMP-2 caused significant upregulation of Sox9 and Noggin expression in these cells. The upregulation of Noggin could be inhibited by introducing antisense oligonucleotides against Sox9 mRNA into the cells. Using mouse limb bud cultures, the role of Sox9 and Noggin during endochondral tissue differentiation was further studied. Treatment of cultures with Sox9 antisense oligonucleotides and/or Noggin protein caused significant alterations in limb morphogenesis and endochondral development. The data suggest that the transcriptional control of Noggin by Sox9 is a potent regulatory mechanism in chondrocyte differentiation.
Zehentner
Barbara Katharina
BK
Roche Pharmaceuticals, Molecular Biology, Roche Diagnostics GmbH, Nonnenwald 2, 82372 Penzberg, Germany.
Haussmann
Anja
A
Burtscher
Helmut
H
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000502:physiology*; D018878:Limb Buds / Q000196:embryology; D051379:Mice; D011506:Proteins / Q000502:physiology*; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000502:physiology*; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D006609:High Mobility Group Proteins; D011506:Proteins; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C527933:Sox9 protein, mouse