Zfp521 antagonizes Runx2, delays osteoblast differentiation in vitro, and promotes bone formation in vivo

Meilin Wu, Eric Hesse, Frederic Morvan, Jian Ping Zhang, Diego Correa, Glenn C. Rowe, Riku Kiviranta, Lynn Neff, William M. Philbrick, William C. Horne, Roland Baron

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Zfp521, a 30 C2H2 Kruppel-like zinc finger protein, is expressed at high levels at the periphery of early mesenchymal condensations prefiguring skeletal elements and in all developing bones in the perichondrium and periosteum, in osteoblast precursors and osteocytes, and in chondroblast precursors and growth plate prehypertrophic chondrocytes. Zfp521 expression in cultured mesenchymal cells is decreased by BMP-2 and increased by PTHrP, which promote and antagonize osteoblast differentiation, respectively. In vitro, Zfp521 overexpression reduces the expression of several downstream osteoblast marker genes and antagonizes osteoblast differentiation. Zfp521 binds Runx2 and represses its transcriptional activity, and Runx2 dose-dependently rescues Zfp521's inhibition of osteoblast differentiation. In contrast, osteocalcin promoter-targeted overexpression of Zfp521 in osteoblasts in vivo results in increased bone formation and bone mass. We propose that Zfp521 regulates the rate of osteoblast differentiation and bone formation during development and in the mature skeleton, in part by antagonizing Runx2.

Original languageEnglish (US)
Pages (from-to)528-536
Number of pages9
JournalBone
Volume44
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

Keywords

  • Bone formation
  • Differentiation
  • Osteoblast
  • Runx2
  • Zfp521

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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