HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 9, 5341-5347, March 3, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/9/5341    most recent M506158200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jadlowiec, J. A. Articles by Sfeir, C. Search for Related Content PubMed PubMed Citation Articles by Jadlowiec, J. A. Articles by Sfeir, C. Social Bookmarking                      What's this?

Extracellular Matrix-mediated Signaling by Dentin Phosphophoryn Involves Activation of the Smad Pathway Independent of Bone Morphogenetic Protein^*

Julie A. Jadlowiec, Xiaoyuan Zhang, Jinhua Li, Phil G. Campbell^¶, and Charles Sfeir¹

From the Department of Oral Medicine and Pathology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, the Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, and the ^¶Institute for Complex Engineered Systems, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213

Cells have ingenious mechanisms for interpreting complex signals from their external microenvironment. Previously, we have shown that phosphophoryn (PP) regulates the expression of bone/dentin marker genes via the integrin/MAPK signaling pathway (Jadlowiec, J., Koch, H., Zhang, X., Campbell, P. G., Seyedain, M., and Sfeir, C. (2004) J. Biol. Chem. 279, 53323–53330). We hypothesize that other signaling pathways important for mineralized tissue morphogenesis such as the Smad pathway could be involved in PP signaling. We determined activation of the Smad pathway in human adult mesenchymal stem cells following treatment with recombinant PP (rPP). We observed that PP enhanced phosphorylation of Smad1 within 30 min and Smad1 translocation to the nucleus within 1 h. PP up-regulated the expression of Smad1 target genes, Smad6, Dlx5, and Runx2. The timing of PP activation of Smad1 implies this is a direct effect; however, we also investigated the possible involvement of bone morphogenetic proteins in PP stimulation of the Smad pathway. PP was shown to up-regulate Bmp-2 gene expression 12 h post-treatment with PP, which is much later than initial detection of Smad1 phosphorylation at 30 min. Furthermore, addition of Noggin did not block Smad1 phosphorylation by PP. We propose that PP could signal via the Smad pathway by either directly stimulating the phosphorylation of Smad1 via integrins or other mechanisms. These might include integrin/bone morphogenetic protein receptor interactions or involvement of PP with other growth factors leading to the modulation of intracellular signaling. It is noteworthy that a non-transforming growth factor- family member activates the Smad pathway. The role of PP in regulating the Smad pathway raises very interesting questions regarding the role of PP during bone and tooth development.

Received for publication, June 6, 2005 , and in revised form, October 12, 2005.

^* This work was supported in part by National Institutes of Health Grant DE016123-01 and by the University of Pittsburgh Central Research Development Fund (to C. S.) and by the Pennsylvania Infrastructure Technology Alliance (to P. G. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Oral Medicine and Pathology, University of Pittsburgh; 693A Salk Hall, 3501 Terrace St., Pittsburgh, PA 15261-1964. Tel.: 412-648-1949, E-mail: csfeir{at}pitt.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Liu, J. Zhou, W. Tang, R. Menard, J. Q. Feng, and L. D. Quarles Pathogenic role of Fgf23 in Dmp1-null mice Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E254 - E261. [Abstract] [Full Text] [PDF]

				S. Chen, J. Gluhak-Heinrich, M. Martinez, T. Li, Y. Wu, H.-H. Chuang, L. Chen, J. Dong, I. Gay, and M. MacDougall Bone Morphogenetic Protein 2 Mediates Dentin Sialophosphoprotein Expression and Odontoblast Differentiation via NF-Y Signaling J. Biol. Chem., July 11, 2008; 283(28): 19359 - 19370. [Abstract] [Full Text] [PDF]

				J. A. Phillippi, E. Miller, L. Weiss, J. Huard, A. Waggoner, and P. Campbell Microenvironments Engineered by Inkjet Bioprinting Spatially Direct Adult Stem Cells Toward Muscle- and Bone-Like Subpopulations Stem Cells, January 1, 2008; 26(1): 127 - 134. [Abstract] [Full Text] [PDF]