Open AccessSuppression of BMP-Smad Signaling Axis-Induced Osteoblastic Differentiation by Small C-terminal Domain Phosphatase 1, a Smad Phosphatase
Author(s) -
Shoichiro Kokabu,
Satoshi Ohte,
Hiroyuki Sasanuma,
Masashi Shin,
Katsumi Yoneyama,
Eri Murata,
Kazuhiro Kanomata,
Junya Nojima,
Yusuke Ono,
Tetsuya Yoda,
Tsuyoshi Fukuda,
Takenobu Katagiri
Publication year - 2011
Publication title -
molecular endocrinology
Language(s) - English
Resource type - Journals
eISSN - 1944-9917
pISSN - 0888-8809
DOI - 10.1210/me.2010-0305
Subject(s) - smad , runx2 , phosphorylation , biology , phosphatase , bone morphogenetic protein 2 , bone morphogenetic protein , alkaline phosphatase , signal transduction , microbiology and biotechnology , gene knockdown , cellular differentiation , osteoblast , smad2 protein , cancer research , biochemistry , apoptosis , gene , enzyme , in vitro
Bone morphogenetic proteins (BMPs) induce osteoblastic differentiation in myogenic cells via the phosphorylation of Smads. Two types of Smad phosphatases--small C-terminal domain phosphatase 1 (SCP1) and protein phosphatase magnesium-dependent 1A--have been shown to inhibit BMP activity. Here, we report that SCP1 inhibits the osteoblastic differentiation induced by BMP-4, a constitutively active BMP receptor, and a constitutively active form of Smad1. The phosphatase activity of SCP1 was required for this suppression, and the knockdown of SCP1 in myoblasts stimulated the osteoblastic differentiation induced by BMP signaling. In contrast to protein phosphatase magnesium-dependent 1A, SCP1 did not reduce the protein levels of Smad1 and failed to suppress expression of the Id1, Id2, and Id3 genes. Runx2-induced osteoblastic differentiation was suppressed by SCP1 without affecting the transcriptional activity or phosphorylation levels of Runx2. Taken together, these findings suggest that SCP1 may inhibit the osteoblastic differentiation induced by the BMP-Smad axis via Runx2 by suppressing downstream effector(s).