J Cell Sci 2007,
PMID: 17374642
Hayashi, Masanori; Nimura, Keisuke; Kashiwagi, Katsunobu; Harada, Taku; Takaoka, Kunio; Kato, Hiroyuki; Tamai, Katsuto; Kaneda, Yasufumi
Basic helix-loop-helix (bHLH) transcription factors are known as key regulators for mesenchymal differentiation. The present study showed that overexpression of Twist-1, a bHLH transcription factor, suppresses bone morphogenetic protein (BMP)-induced osteoblast differentiation, and downregulation of endogenous Twist-1 enhances BMP signaling. Maximal inhibition of BMP signaling was observed when Twist-1 was bound to E47, which markedly enhanced the stability of Twist-1. Co-immunoprecipitation assays revealed that Twist-1 formed a complex with Smad4 and histone deacetylase (HDAC) 1 in MC3T3-E1 cells stably expressing Twist-1. With trichostatin, an HDAC inhibitor, osteogenic factors such as alkaline phosphatase, Runx2 and osteopontin increased. Those results suggested that Twist-1 inhibited BMP signaling by recruiting HDAC1 to Smad4. Furthermore, the inhibitory effects of Twist-1 on BMP signaling were overcome by Id1 through induction of Twist-1 degradation. These findings suggest that Twist-1 can act as an inhibitor of BMP signaling, and Id1 can regulate BMP signaling through a positive feedback loop repressing Twist-1 function. These two molecules may therefore regulate differentiation of mesenchymal cells into progeny such as osteoblasts by controlling BMP signaling.
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Text Mining Data
BMP ⊣ Twist-1: "
The present study showed that overexpression of Twist-1, a bHLH transcription factor, suppresses bone morphogenetic protein ( BMP ) -induced osteoblast differentiation, and downregulation of endogenous
Twist-1 enhances
BMP signaling
"
BMP ⊣ Twist-1: "
Those results suggested that Twist-1 inhibited BMP signaling by recruiting HDAC1 to Smad4
"
BMP ⊣ HDAC1: "
Those results suggested that Twist-1 inhibited BMP signaling by recruiting HDAC1 to Smad4
"
BMP — Twist-1: "
Furthermore, the inhibitory effects of Twist-1 on BMP signaling were overcome by Id1 through induction of Twist-1 degradation
"
BMP → Id1: "
These findings suggest that Twist-1 can act as an inhibitor of BMP signaling, and Id1 can regulate BMP signaling through a positive feedback loop repressing Twist-1 function
"
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