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

J. Biol. Chem., Vol. 278, Issue 1, 438-443, January 3, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/1/438    most recent M208292200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sheu, T.-J. Articles by Puzas, J. E. Search for Related Content PubMed PubMed Citation Articles by Sheu, T.-J. Articles by Puzas, J. E. Social Bookmarking                      What's this?

A Phage Display Technique Identifies a Novel Regulator of Cell Differentiation^*

Tzong-Jen Sheu, Edward M. Schwarz, Daniel A. Martinez^§, Regis J. O'Keefe, Randy N. Rosier, Michael J. Zuscik, and J. Edward Puzas^¶

From the  Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 and the ^§ Connective Tissue Physiology Laboratory, Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5001

The formation of new bone during the process of bone remodeling occurs almost exclusively at sites of prior bone resorption. In an attempt to discover what regulatory pathways are utilized by osteoblasts to effect this site-specific formation event we probed components of an active bone resorption surface with an osteoblast phage expression library. In these experiments primary cultures of rat osteoblasts were used to construct a phage display library in T7 phage. Tartrate-resistant acid phosphatase (type V) (TRAP) was used as the bait in a biopanning procedure. 40 phage clones with very high affinity for TRAP were sequenced, and of the clones with multiple consensus sequences we identified a regulatory protein that modulates osteoblast differentiation. This protein is the TGF receptor-interacting protein (TRIP-1). Our data demonstrate that TRAP activation of TRIP-1 evokes a TGF-like differentiation process. Specifically, TRIP-1 activation increases the activity and expression of osteoblast alkaline phosphatase, osteoprotegerin, collagen, and Runx2. Moreover, we show that TRAP interacts with TRIP intracellularly, that activation of the TGF type II receptor by TRIP-1 occurs in the presence of TRAP and that the differentiation process is mediated through the Smad2/3 pathway. A final experiment demonstrates that osteoblasts, when cultured in osteoclast lacunae containing TRAP, rapidly and specifically differentiate into a mature bone-forming phenotype. We hypothesize that binding to TRAP may be one mechanism by which the full osteoblast phenotype is expressed during the process of bone remodeling.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				R. Garimella, S. E. Tague, J. Zhang, F. Belibi, N. Nahar, B. H. Sun, K. Insogna, J. Wang, and H. C. Anderson Expression and Synthesis of Bone Morphogenetic Proteins by Osteoclasts: A Possible Path to Anabolic Bone Remodeling J. Histochem. Cytochem., June 1, 2008; 56(6): 569 - 577. [Abstract] [Full Text] [PDF]

				E. J. Slootweg, H. J.H.G. Keller, M. A. Hink, J. W. Borst, J. Bakker, and A. Schots Fluorescent T7 display phages obtained by translational frameshift Nucleic Acids Res., November 6, 2006; 34(20): e137 - e137. [Abstract] [Full Text] [PDF]

				J. Ljusberg, Y. Wang, P. Lang, M. Norgard, R. Dodds, K. Hultenby, B. Ek-Rylander, and G. Andersson Proteolytic Excision of a Repressive Loop Domain in Tartrate-resistant Acid Phosphatase by Cathepsin K in Osteoclasts J. Biol. Chem., August 5, 2005; 280(31): 28370 - 28381. [Abstract] [Full Text] [PDF]