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KMID : 0578320070240010139
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Molecules and Cells
2007 Volume.24 No. 1 p.139 ~ p.147
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Suppression of ADAM 10-induced Delta-1 Shedding Inhibits Cell Proliferation During the Chondro-Inhibitory Action of TGF-β3
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Jin Eun-Jung
Choi Young-Ae
Sonn Jong-Kyung
Kang Shin-Sung
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Abstract
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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-β 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-β 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-β3. The suppression of mesenchymal cell proliferation induced by TGF-β 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-β 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.
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KEYWORD
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ADAM 10, Chondrogenesis, Delta-1, Notch-1, TGF-β3
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