Use of a phage display technique to identify potential osteoblast binding sites within osteoclast lacunae

Tzong Jen Sheu, Edward M. Schwarz, Regis J. O'Keefe, Randy N. Rosier, J. Edward Puzas

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

There is a temporal coupling between the processes of bone resorption and bone formation in normal skeletal remodeling. That is, osteoblastic activity usually follows episodes of osteoclastic activity. However, what has not been universally appreciated is that there also is a spatial coupling between these processes. Bone formation only occurs in the immediate vicinity of the resorptive event. In this study, we describe a phage display technique that has been used to identify the mechanisms by which osteoblasts recognize components of the prior resorbed lacunar surface. Using a type V tartrate- resistant acid phosphatase (TRAP) as the bait and a random peptide M13 phage display library as the probe, we have identified specific sequences that show a very high affinity for TRAP. One of these peptides, designated clone 5, has a subnanomolar Kd for TRAP, interacts with TRAP in a Far-Western assay, binds exclusively to TRAP within osteoclast lacunae, is present in osteoblasts, and can effectively block osteoblast binding to resorption surfaces. The clone 5 peptide shows a high homology to glypican 4 (GPC4), a proteoglycan attachment receptor found in a number of cell types.

Original languageEnglish
Pages (from-to)915-922
Number of pages8
JournalJournal of Bone and Mineral Research
Volume17
Issue number5
DOIs
StatePublished - 2002

Keywords

  • Glypican 4
  • Lacunae
  • Osteoblast
  • Osteoclast
  • Phage display

Fingerprint Dive into the research topics of 'Use of a phage display technique to identify potential osteoblast binding sites within osteoclast lacunae'. Together they form a unique fingerprint.

Cite this