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Activation of the ERK pathway in osteoblastic cells, role of gremlin and BMP‐2
Author(s) -
Zanotti Stefano,
SmerdelRamoya Anna,
Stadmeyer Lisa,
Canalis Ernesto
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21715
Subject(s) - smad , mapk/erk pathway , bone morphogenetic protein , microbiology and biotechnology , bone morphogenetic protein 2 , stromal cell , phosphorylation , bmpr2 , chemistry , signal transduction , osteoblast , cancer research , biology , in vitro , biochemistry , gene
Abstract Gremlin is a glycoprotein that binds and antagonizes the actions of bone morphogenetic proteins (BMPs) ‐2, ‐4, and ‐7. Gremlin appears to activate the extracellular regulated kinase (ERK) pathway in endothelial and tumor cells, and as a consequence to have direct cellular effects. To determine whether gremlin has direct effects in osteoblasts, independent of its BMP binding activity, we examined its effects in ST‐2 murine stromal cell lines and in primary cultures of murine calvarial osteoblasts. Gremlin did not activate Signaling mothers against decapentaplegic (Smad), and suppressed the BMP‐2 induced Smad 1/5/8 phosphorylation and the transactivation of the BMP/Smad reporter construct 12xSBE‐Oc‐pGL3, confirming its BMPs antagonizing activity. Neither gremlin nor BMP‐2 induced ERK 1/2 activation in ST‐2 cells or calvarial osteoblasts. Moreover, slight changes in culture conditions induced the phosphorylation of ERK independent from BMP or gremlin exposure. In conclusion, gremlin inhibits BMP‐2 signaling and activity, and does not have independent actions on ERK signaling in osteoblasts. Consequently, gremlin activity in osteoblasts can be attributed only to its BMP antagonizing effects. J. Cell. Biochem. 104: 1421–1426, 2008. © 2008 Wiley‐Liss, Inc.