Runx2: A master organizer of gene transcription in developing and maturing osteoblasts

Tania M. Schroeder, Eric D. Jensen, Jennifer J. Westendorf

Research output: Contribution to journalReview articlepeer-review

215 Scopus citations

Abstract

Runx2 is essential for osteoblast development and proper bone formation. A member of the Runt domain family of transcription factors, Runx2 binds specific DNA sequences to regulate transcription of numerous genes and thereby control osteoblast development from mesenchymal stem cells and maturation into osteocytes. Although necessary for gene transcription and osteoblast development, Runx2 is not sufficient for optimal gene expression or bone formation. Runx2 cooperates with numerous proteins, including transcription factors and cofactors, is posttranslationally modified, and associates with the nuclear matrix to integrate a variety of signals and organize crucial events during osteoblast development and maturation. Consistent with its role as a master organizer, alterations in Runx2 expression levels are associated with skeletal diseases. Runx2 haploinsufficiency causes cleidocranial dysplasia, while Runx2 overexpression is common in many bone-metastatic cancers. In this review, we summarize the molecular mechanisms by which Runx2 integrates signals through coregulatory interactions, and discuss how its role as a master organizer may shift depending on promoter structure, developmental cues, and cellular context.

Original languageEnglish (US)
Pages (from-to)213-225
Number of pages13
JournalBirth Defects Research Part C - Embryo Today: Reviews
Volume75
Issue number3
DOIs
StatePublished - Sep 2005

Keywords

  • Cbfa1
  • Nuclear matrix
  • Osteogenesis
  • Runt domain

ASJC Scopus subject areas

  • Embryology
  • Developmental Biology

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