Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis

Rick B. Vega, Koichi Matsuda, Junyoung Oh, Ana C. Barbosa, Xiangli Yang, Eric Meadows, John McAnally, Chris Pomajzl, John M. Shelton, James A. Richardson, Gerard Karsenty, Eric N. Olson

Research output: Contribution to journalArticle

552 Citations (Scopus)

Abstract

Histone deacetylases (HDACs) modulate cell growth and differentiation by governing chromatin structure and repressing the activity of specific transcription factors. We showed previously that HDAC9 acts as a negative regulator of cardiomyocyte hypertrophy and skeletal muscle differentiation. Here we report that HDAC4, which is expressed in prehypertrophic chondrocytes, regulates chondrocyte hypertrophy and endochondral bone formation by interacting with and inhibiting the activity of Runx2, a transcription factor necessary for chondrocyte hypertrophy. HDAC4-null mice display premature ossification of developing bones due to ectopic and early onset chondrocyte hypertrophy, mimicking the phenotype that results from constitutive Runx2 expression in chondrocytes. Conversely, overexpression of HDAC4 in proliferating chondrocytes in vivo inhibits chondrocyte hypertrophy and differentiation, mimicking a Runx2 loss-of-function phenotype. These results establish HDAC4 as a central regulator of chondrocyte hypertrophy and skeletogenesis and suggest general roles for class II HDACs in the control of cellular hypertrophy.

Original languageEnglish (US)
Pages (from-to)555-566
Number of pages12
JournalCell
Volume119
Issue number4
DOIs
StatePublished - Nov 12 2004

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Histone Deacetylases
Chondrocytes
Hypertrophy
Bone
Transcription Factors
Cell growth
Chromatin
Muscle
Osteogenesis
Phenotype
Cardiac Myocytes
Cell Differentiation
Skeletal Muscle
Bone and Bones
Growth

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Vega, R. B., Matsuda, K., Oh, J., Barbosa, A. C., Yang, X., Meadows, E., ... Olson, E. N. (2004). Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell, 119(4), 555-566. https://doi.org/10.1016/j.cell.2004.10.024

Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. / Vega, Rick B.; Matsuda, Koichi; Oh, Junyoung; Barbosa, Ana C.; Yang, Xiangli; Meadows, Eric; McAnally, John; Pomajzl, Chris; Shelton, John M.; Richardson, James A.; Karsenty, Gerard; Olson, Eric N.

In: Cell, Vol. 119, No. 4, 12.11.2004, p. 555-566.

Research output: Contribution to journalArticle

Vega, RB, Matsuda, K, Oh, J, Barbosa, AC, Yang, X, Meadows, E, McAnally, J, Pomajzl, C, Shelton, JM, Richardson, JA, Karsenty, G & Olson, EN 2004, 'Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis', Cell, vol. 119, no. 4, pp. 555-566. https://doi.org/10.1016/j.cell.2004.10.024
Vega RB, Matsuda K, Oh J, Barbosa AC, Yang X, Meadows E et al. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell. 2004 Nov 12;119(4):555-566. https://doi.org/10.1016/j.cell.2004.10.024
Vega, Rick B. ; Matsuda, Koichi ; Oh, Junyoung ; Barbosa, Ana C. ; Yang, Xiangli ; Meadows, Eric ; McAnally, John ; Pomajzl, Chris ; Shelton, John M. ; Richardson, James A. ; Karsenty, Gerard ; Olson, Eric N. / Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. In: Cell. 2004 ; Vol. 119, No. 4. pp. 555-566.
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