Suppression of BMP-Smad signaling axis-induced osteoblastic differentiation by small C-terminal domain phosphatase 1, a Smad phosphatase.
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).
Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
Shoichiro
S
Kokabu
Satoshi
S
Ohte
Hiroki
H
Sasanuma
Masashi
M
Shin
Katsumi
K
Yoneyama
Eiko
E
Murata
Kazuhiro
K
Kanomata
Junya
J
Nojima
Yusuke
Y
Ono
Tetsuya
T
Yoda
Toru
T
Fukuda
Takenobu
T
Katagiri
D000818:Animals; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism*
D055415:Bone Morphogenetic Protein 4; D050659:Core Binding Factor Alpha 1 Subunit; D051898:Smad1 Protein; D010749:Phosphoprotein Phosphatases
J Cell Biol. 1994 Dec;127(6 Pt 1):1755-66
7798324
Cell. 1996 May 17;85(4):489-500
8653785
J Biol Chem. 2009 Mar 13;284(11):7149-56
18684712
Biotechniques. 1996 Dec;21(6):1013-5
8969825
Cell. 2006 Jun 2;125(5):915-28
16751101
Nature. 1999 Aug 12;400(6745):687-93
10458166
Genes Cells. 2002 Sep;7(9):949-60
12296825
Mol Cell Biol. 2002 May;22(9):2893-905
11940648
J Biol Chem. 2010 May 14;285(20):15577-15586
20231279
Biochem Biophys Res Commun. 2008 Dec 19;377(3):905-9
18952055
J Biol Chem. 2003 Jul 11;278(28):26078-85
12721286
Science. 1965 Nov 12;150(3698):893-9
5319761
Cell. 1997 May 30;89(5):747-54
9182762
Biochem Biophys Res Commun. 2006 Jul 7;345(3):1224-31
16716261
Cell Tissue Res. 1996 Apr;284(1):9-17
8601300
Mol Cell Biol. 1995 Apr;15(4):1858-69
7891679
Mol Cell Biol. 2000 Dec;20(23):8783-92
11073979
Dev Dyn. 2007 Jul;236(7):1876-90
17497678
Cell. 2007 Nov 30;131(5):980-93
18045539
J Biol Chem. 2002 Feb 1;277(5):3176-85
11700304
J Biol Chem. 2006 Dec 1;281(48):36526-32
16931515
J Biol Chem. 1999 Jul 9;274(28):19838-45
10391928
J Biol Chem. 2006 Dec 29;281(52):40412-9
17085434
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12938-43
9371779
Nat Genet. 2006 May;38(5):525-7
16642017
Cell. 2002 Jan 11;108(1):17-29
11792318
Cytokine Growth Factor Rev. 2005 Jun;16(3):251-63
15871923
J Bone Miner Res. 2010 Mar;25(3):653-60
19594322
J Biol Chem. 1998 Jan 23;273(4):1872-9
9442019
Biochem Biophys Res Commun. 2005 Mar 18;328(3):651-7
15694398
Science. 2005 Jan 28;307(5709):596-600
15681389
Nature. 1997 Oct 9;389(6651):618-22
9335504
Dev Biol. 2010 Jan 1;337(1):29-41
19835858
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11940-5
16882717