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KMID : 0578320100290040425
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Molecules and Cells
2010 Volume.29 No. 4 p.425 ~ p.432
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TGF-β3 Inhibits Chondrogenesis by Suppressing Precartilage Condensation through Stimulation of N-cadherin Shedding and Reduction of cRREB-1 Expression
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Jin Eun-Jung
Park Kwang-Sook
Kim Dong-Kyun
Lee Young-Sup
Sonn Jong-Kyung
Jung Jae-Chang
Bang Ok-Sun
Kang Shin-Sung
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Abstract
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Transforming growth factor-β (TGF-β) plays crucial roles in controlling cell differentiation and maintaining tissue integrity. Previously we reported that TGF-β3 treatment decreased the mRNA expression of the gap junction pro-tein, connexin 43 as well as cell number, which lead to the inhibition of chondrogenic condensation in cultured chick leg bud mesenchymal cells. The present study demonstrates that TGF-β3 can induce cleavage in the ectodomain of neuronal cadherin (N-cadherin) at the initiation stage of chondrogenesis and reduce cell numbers, cellular adhesion and the expression level of connexin 43. Differential displayed PCR (DD-PCR) comparison of adherent- and non-adherent chick leg chondrogenic progenitor cells showed increased expression of the chick ras-responsive element binding transcription factor, cRREB-1, in adherent cells. In chick leg bud mesenchymal cells, cRREB-1 transcription was inhibited by TGF-β3 at the early stage of chondrogenesis. Small interfering RNA (siRNA)-mediated knockdown of cRREB-1 reduced cell numbers, cellular adhesion, and the expression level of connexin 43 resulting in the inhibition of precartilage condensation. Taken together, these findings indicate that TGF-β3 mediates the inhibitory signal necessary for precartilage condensation by stimulating N-cadherin shedding and reducing cRREB-1 expression levels.
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KEYWORD
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chondrogenesis, ectodomain shedding, N-cadherin, RREB-1, TGF-β3
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