Suppression of ADAM 10-induced Delta-1 Shedding Inhibits Cell Proliferation During the Chondro-Inhibitory Action of TGF-β3

  • Jin, Eun-Jung (Department of Biology, College of Natural Sciences (BK21), Kyungpook National University) ;
  • Choi, Young-Ae (Department of Biology, College of Natural Sciences (BK21), Kyungpook National University) ;
  • Sonn, Jong-Kyung (Department of Biology, College of Natural Sciences (BK21), Kyungpook National University) ;
  • Kang, Shin-Sung (Department of Biology, College of Natural Sciences (BK21), Kyungpook National University)
  • Received : 2007.05.28
  • Accepted : 2007.07.24
  • Published : 2007.08.31

Abstract

Although transforming growth factors (TGFs) are implicated in the process of endochondral ossification, which is initiated by the differentiation of mesenchymal cells into chondrocytes, it is not clear how $TGF-{\beta}3$ regulates the chondrogenic differentiation of limb bud mesenchymal cells. Here, differential display polymerase chain reaction (DD-PCR) screening and RT-PCR analysis revealed that transcripts of A Disintegrin And Metalloprotease 10 (ADAM 10) decreased during the chondro-inhibitory action of $TGF-{\beta}3$ on cultured chick leg bud mesenchymal cells. Electroporation of ADAM 10 morpholino antisense oligonucleotides inhibited the ectodomain shedding of delta-1, and cell proliferation and subsequent precartilage condensation, in a manner similar to that caused by $TGF-{\beta}3$. The suppression of mesenchymal cell proliferation induced by $TGF-{\beta}3$ and ADAM 10 morpholino antisense oligonucleotides was reversed by activation of ADAM 10 with phorbol 12-myristate 13-acetate (PMA) or knockdown of Notch-1 with siRNA. Collectively, these data indicate that, in cultured chick leg bud mesenchyme cells, $TGF-{\beta}3$ downregulates ADAM 10 and inhibits cell proliferation and subsequent precartilage condensation by inhibiting the ectodomain shedding of delta-1, and that this results in the activation of Notch signaling.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation (KOSEF)

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