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BMP‐2 regulation of PTHrP and osteoclastogenic factors during osteoblast differentiation of C2C12 cells
Author(s) -
Susperregui Antonio R.G.,
Viñals Francesc,
Ho Patricia W.M.,
Gillespie Matthew T.,
Martin T. John,
Ventura Francesc
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21389
Subject(s) - c2c12 , osteoblast , runx2 , microbiology and biotechnology , paracrine signalling , mesenchymal stem cell , chemistry , rankl , bone morphogenetic protein 2 , smad , bone morphogenetic protein , signal transduction , cellular differentiation , medicine , biology , myocyte , receptor , gene , biochemistry , in vitro , myogenesis , activator (genetics)
Abstract Bone morphogenetic protein‐2 (BMP‐2) is strongly involved in the induction of osteoblast differentiation from mesenchymal cell precursors, as well as in enhancing bone matrix production by osteoblastic cells. Likewise, the osteoporotic phenotype of PTHrP deficient mice makes clear the importance of this paracrine regulator in bone physiology. Here, we report that BMP‐2 rapidly down‐regulated PTHrP gene expression through a transcriptional mechanism in pluripotent mesenchymal C2C12 cells, whereas BMP‐2 increased expression of PTHrP receptor. PTHrP did not significantly alter the BMP‐dependent Smad transcriptional pathway. Similarly, PTHrP did not significantly modify the BMP‐regulated expression of RANKL or OPG, cytokines involved in osteoclastogenesis. More importantly, addition of PTHrP, through the PKA signaling pathway, partially prevented the BMP‐dependent induction of some osteogenic markers such as Runx2 and Osterix in C2C12 cells. Our data suggest that BMP‐2 down‐regulation of PTHrP could facilitate terminal differentiation of osteoblasts. J. Cell. Physiol. 216: 144–152, 2008. © 2008 Wiley‐Liss, Inc.