Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass

Yankel Gabet, Sanjeev K. Baniwal, Nathalie Leclerc, Yunfan Shi, Alice E. Kohn-Gabet, Jon Cogan, Alexis Dixon, Marilyn Bachar, Lixin Guo, Jack Turman, Baruch Frenkel

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Krox20/EGR2, one of the 4 early growth response genes, is a highly conserved transcription factor implicated in hind-brain development, peripheral nerve myelination, tumor suppression, and monocyte/macrophage cell fate determination. Here, we established a novel role for Krox20 in postnatal skeletal metabolism. Microcomputed tomographic analysis of 4- and 8-week-old mice revealed a low bone mass phenotype (LBM) in both the distal femur and the vertebra of Krox20+/- mice. This was attributable to accelerated bone resorption as demonstrated in vivo by increased osteoclast number and serum C-terminal telopeptides, a marker for collagen degradation. Krox20 haploinsufficiency did not reduce bone formation in vivo, nor did it compromise osteoblast differentiation in vitro. In contrast, growth and differentiation were significantly stimulated in preosteoclast cultures derived from Krox20 +/- splenocytes, suggesting that the LBM is attributable to Krox20 haploinsufficiency in the monocytic lineage. Furthermore, Krox20 silencing in preosteoclasts increased cFms expression and response to macrophage colony-stimulating factor, leading to a cell-autonomous stimulation of cell-cycle progression. Our data indicate that the antimitogenic role of Krox20 in preosteoclasts is the predominant mechanism underlying the LBM phenotype of Krox20-deficient mice. Stimulation of Krox20 expression in preosteoclasts may present a viable therapeutic strategy for high-turnover osteoporosis.

Original languageEnglish (US)
Pages (from-to)3964-3971
Number of pages8
JournalBlood
Volume116
Issue number19
DOIs
StatePublished - Nov 11 2010
Externally publishedYes

Fingerprint

Cell growth
Haploinsufficiency
Cell Differentiation
Bone
Bone and Bones
Peripheral Nervous System Neoplasms
Growth
Rhombencephalon
Macrophage Colony-Stimulating Factor
Osteoclasts
Bone Resorption
Osteoblasts
Osteogenesis
Femur
Osteoporosis
Monocytes
Cell Cycle
Spine
Transcription Factors
Collagen

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Gabet, Y., Baniwal, S. K., Leclerc, N., Shi, Y., Kohn-Gabet, A. E., Cogan, J., ... Frenkel, B. (2010). Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass. Blood, 116(19), 3964-3971. https://doi.org/10.1182/blood-2010-01-263830

Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass. / Gabet, Yankel; Baniwal, Sanjeev K.; Leclerc, Nathalie; Shi, Yunfan; Kohn-Gabet, Alice E.; Cogan, Jon; Dixon, Alexis; Bachar, Marilyn; Guo, Lixin; Turman, Jack; Frenkel, Baruch.

In: Blood, Vol. 116, No. 19, 11.11.2010, p. 3964-3971.

Research output: Contribution to journalArticle

Gabet, Y, Baniwal, SK, Leclerc, N, Shi, Y, Kohn-Gabet, AE, Cogan, J, Dixon, A, Bachar, M, Guo, L, Turman, J & Frenkel, B 2010, 'Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass', Blood, vol. 116, no. 19, pp. 3964-3971. https://doi.org/10.1182/blood-2010-01-263830
Gabet, Yankel ; Baniwal, Sanjeev K. ; Leclerc, Nathalie ; Shi, Yunfan ; Kohn-Gabet, Alice E. ; Cogan, Jon ; Dixon, Alexis ; Bachar, Marilyn ; Guo, Lixin ; Turman, Jack ; Frenkel, Baruch. / Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass. In: Blood. 2010 ; Vol. 116, No. 19. pp. 3964-3971.
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