Histone deacetylase 7 (Hdac7) suppresses chondrocyte proliferation and β-catenin activity during endochondral ossification

Elizabeth W. Bradley, Lomeli R. Carpio, Eric N. Olson, Jennifer J. Westendorf

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Histone deacetylases (Hdacs) regulate endochondral ossification by suppressing gene transcription and modulating cellular responses to growth factors and cytokines. We previously showed that Hdac7 suppresses Runx2 activity and osteoblast differentiation. In this study, we examined the role of Hdac7 in postnatal chondrocytes. Hdac7 was highly expressed in proliferating cells within the growth plate. Postnatal tissue-specific ablation of Hdac7 with a tamoxifen-inducible collagen type 2a1-driven Cre recombinase increased proliferation and β-catenin levels in growth plate chondrocytes and expanded the proliferative zone. Similar results were obtained in primary chondrocyte cultures where Hdac7 was deleted with adenoviral-Cre. Hdac7 bound β-catenin in proliferating chondrocytes, but stimulation of chondrocyte maturation promoted the translocation of Hdac7 to the cytoplasm where it was degraded by the proteasome. As a result, β-catenin levels and transcription activity increased in the nucleus. These data demonstrate that Hdac7 suppresses proliferation and β-catenin activity in chondrocytes. Reducing Hdac7 levels in early chondrocytes may promote the expansion and regeneration of cartilage tissues.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalJournal of Biological Chemistry
Volume290
Issue number1
DOIs
StatePublished - Jan 2 2015

Fingerprint

Catenins
Histone Deacetylases
Chondrocytes
Osteogenesis
Growth Plate
Transcription
Tissue
Osteoblasts
Cartilage
Proteasome Endopeptidase Complex
Tamoxifen
Ablation
Regeneration
Intercellular Signaling Peptides and Proteins
Cytoplasm
Collagen
Genes
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Histone deacetylase 7 (Hdac7) suppresses chondrocyte proliferation and β-catenin activity during endochondral ossification. / Bradley, Elizabeth W.; Carpio, Lomeli R.; Olson, Eric N.; Westendorf, Jennifer J.

In: Journal of Biological Chemistry, Vol. 290, No. 1, 02.01.2015, p. 118-126.

Research output: Contribution to journalArticle

Bradley, Elizabeth W. ; Carpio, Lomeli R. ; Olson, Eric N. ; Westendorf, Jennifer J. / Histone deacetylase 7 (Hdac7) suppresses chondrocyte proliferation and β-catenin activity during endochondral ossification. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 1. pp. 118-126.
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