Neurogenesin-1 differentially inhibits the osteoblastic differentiation by bone morphogenetic proteins in C2C12 cells

Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Hamamatsu 431-3192, Japan.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 07/2006; 344(3):786-91. DOI: 10.1016/j.bbrc.2006.03.195
Source: PubMed


Bone morphogenetic protein (BMP) antagonists regulate the pleiotropic actions of BMPs by binding to BMPs. We previously isolated the Neurogenesin-1 (Ng1) gene and found that Ng1 protein induces neuronal differentiation in the brain. In this study, we found that Ng1 was expressed in the primordial cells of the skeleton and investigated whether Ng1 protein inhibited the BMP action to induce osteoblastic differentiation in C2C12 myoblasts. Interestingly, Ng1 protein inhibited the BMP7-induced alkaline phosphatase activity while it did not inhibit the BMP2-induced activity. All data suggest that Ng1 protein plays an important role in the embryonic bone formation by differentially regulating BMPs.

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    • "Chordin-like 1 (CHRDL1), also known as neuralin-1 (Coffinier et al., 2001), ventroptin (Sakuta et al., 2001) and neurogenesin-1 (Ueki et al., 2003), is a secreted BMP-binding protein that contains three von Willebrand type C repeats with homology to chordin (Nakayama et al., 2001). Direct interaction of CHRDL1 with BMP4 has been demonstrated by several groups, and weaker interactions with other BMPs and TGF-beta superfamily members have also been described (Nakayama et al., 2001; Sakuta et al., 2001; Chandra et al., 2006; Kane et al., 2008). Inhibition of BMP4 activity by CHRDL1 has been demonstrated in vivo by the ability of exogenous CHRDL1 to induce secondary axis formation in Xenopus embryos, which was rescued by co-injection by BMP4 (Nakayama et al., 2001; Sakuta et al., 2001), and in vitro by antagonizing the inhibitory effect of BMP4 in angiogenesis assays (Kane et al., 2008). "
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