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The bone morphogenetic protein antagonist Noggin is regulated by Sox9 during endochondral differentiation
Author(s) -
Zehentner Barbara Katharina,
Haussmann Anja,
Burtscher Helmut
Publication year - 2002
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1046/j.1440-169x.2002.00616.x
Subject(s) - noggin , chondrogenesis , microbiology and biotechnology , endochondral ossification , bone morphogenetic protein 7 , chondrocyte , bone morphogenetic protein 2 , chemistry , bone morphogenetic protein , sox9 , biology , medicine , mesenchymal stem cell , anatomy , cartilage , gene expression , biochemistry , in vitro , gene
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.