Regulatory Controls for Osteoblast Growth and Differentiation

Role of Runx/Cbfa/AML Factors

Jane B. Lian, Amjad Javed, S. Kaleem Zaidi, Christopher Lengner, Martin Montecino, Andre J van Wijnen, Janet L. Stein, Gary S. Stein

Research output: Contribution to journalArticle

346 Citations (Scopus)

Abstract

Formation of skeletal elements during embryogenesis and the dynamic remodeling of bone in the adult involve an exquisite interplay of developmental cues, signaling proteins, transcription factors, and their coregulatory proteins that support differentiation of osteogenic lineage cells from the initial mesenchymal progenitor cell to the mature osteocyte in mineralized connective tissue. As regulatory factors continue to be identified, the complexity of the molecular mechanisms that control gene expression in osteoblast lineage cells and drive the osteoblast maturation process are being further appreciated. A central regulator of bone formation is the Runx2 (Cbfa1/AML3) transcription factor which fulfills its role as a master regulatory switch through unique properties for mediating the temporal activation and/or repression of cell growth and phenotypic genes as osteoblasts progress through stages of differentiation. This review examines the multifunctional roles of Runx2 during osteogenesis. Runx2 functions as a "platform protein" that interacts with a spectrum of coregulatory proteins to provide a combinatorial mechanism for integrating cell signaling pathways required for osteoblast differentiation and the tissue-specific regulation of gene expression. In a broader context, it has recently been appreciated that the Runx1 hematopoietic factor and the Runx3 gene associated with neural and gut development are also expressed in the skeleton, although at present our knowledge of their roles in bone formation is limited. Here we discuss the biological functions of Runx factors in promoting cell fate determination and lineage progression, which include (1) regulating gene activation and repression through coregulatory protein interactions and by supporting chromatin remodeling; (2) integrating ECM signaling and cues from developmental, hormonal, and signal transduction pathways by formation of complexes organized in subnuclear domains; and (3) mediating cell growth control. Last, a comprehensive understanding of Runx functions in the skeleton must consider the regulatory mechanisms that control Runx2 transcription and its functional activity through posttranslational modifications.

Original languageEnglish (US)
Pages (from-to)1-41
Number of pages41
JournalCritical Reviews in Eukaryotic Gene Expression
Volume14
Issue number1-2
StatePublished - 2004
Externally publishedYes

Fingerprint

Osteoblasts
Growth
Osteogenesis
Proteins
Skeleton
Cues
Core Binding Factor Alpha 1 Subunit
Osteocytes
Chromatin Assembly and Disassembly
Bone Remodeling
Gene Expression Regulation
Post Translational Protein Processing
Mesenchymal Stromal Cells
Connective Tissue
Transcriptional Activation
Genes
Embryonic Development
Signal Transduction
Transcription Factors
Gene Expression

Keywords

  • Cbfa1/AML3/Runx2
  • Chromatin remodeling
  • Combinatorial mechanisms
  • Gene transcription
  • Genomic organization
  • Nuclear targeting
  • Osteocalcin
  • Runx coregulatory proteins
  • Runx1
  • Runx3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Lian, J. B., Javed, A., Zaidi, S. K., Lengner, C., Montecino, M., van Wijnen, A. J., ... Stein, G. S. (2004). Regulatory Controls for Osteoblast Growth and Differentiation: Role of Runx/Cbfa/AML Factors. Critical Reviews in Eukaryotic Gene Expression, 14(1-2), 1-41.

Regulatory Controls for Osteoblast Growth and Differentiation : Role of Runx/Cbfa/AML Factors. / Lian, Jane B.; Javed, Amjad; Zaidi, S. Kaleem; Lengner, Christopher; Montecino, Martin; van Wijnen, Andre J; Stein, Janet L.; Stein, Gary S.

In: Critical Reviews in Eukaryotic Gene Expression, Vol. 14, No. 1-2, 2004, p. 1-41.

Research output: Contribution to journalArticle

Lian, JB, Javed, A, Zaidi, SK, Lengner, C, Montecino, M, van Wijnen, AJ, Stein, JL & Stein, GS 2004, 'Regulatory Controls for Osteoblast Growth and Differentiation: Role of Runx/Cbfa/AML Factors', Critical Reviews in Eukaryotic Gene Expression, vol. 14, no. 1-2, pp. 1-41.
Lian JB, Javed A, Zaidi SK, Lengner C, Montecino M, van Wijnen AJ et al. Regulatory Controls for Osteoblast Growth and Differentiation: Role of Runx/Cbfa/AML Factors. Critical Reviews in Eukaryotic Gene Expression. 2004;14(1-2):1-41.
Lian, Jane B. ; Javed, Amjad ; Zaidi, S. Kaleem ; Lengner, Christopher ; Montecino, Martin ; van Wijnen, Andre J ; Stein, Janet L. ; Stein, Gary S. / Regulatory Controls for Osteoblast Growth and Differentiation : Role of Runx/Cbfa/AML Factors. In: Critical Reviews in Eukaryotic Gene Expression. 2004 ; Vol. 14, No. 1-2. pp. 1-41.
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