Histone deacetylase 3 is required for maintenance of bone mass during aging

Meghan E. McGee-Lawrence, Elizabeth W. Bradley, Amel Dudakovic, Samuel W. Carlson, Zachary C. Ryan, Rajiv Kumar, Mahrokh Dadsetan, Michael J. Yaszemski, Qingshan Chen, Kai Nan An, Jennifer J. Westendorf

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Histone deacetylase 3 (Hdac3) is a nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression. Hdac3 interacts with bone-related transcription factors and co-factors such as Runx2 and Zfp521, and thus is poised to play a key role in the skeletal system. To understand the role of Hdac3 in osteoblasts and osteocytes, Hdac3 conditional knockout (CKO) mice were created with the osteocalcin (OCN) promoter driving Cre expression. Hdac3 CKO OCN mice were of normal size and weight, but progressively lost trabecular and cortical bone mass with age. The Hdac3 CKO OCN mice exhibited reduced cortical bone mineralization and material properties and suffered frequent fractures. Bone resorption was lower, not higher, in the Hdac3 CKO OCN mice, suggesting that primary defects in osteoblasts caused the reduced bone mass. Indeed, reductions in bone formation were observed. Osteoblasts and osteocytes from Hdac3 CKO OCN mice showed increased DNA damage and reduced functional activity in vivo and in vitro. Thus, Hdac3 expression in osteoblasts and osteocytes is essential for bone maintenance during aging.

Original languageEnglish (US)
Pages (from-to)296-307
Number of pages12
JournalBone
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2013

Bibliographical note

Funding Information:
The NIAMS supported this work ( R01 AR048147 , T32 AR056950 , F32 AR60140 , and F32 AR61873 ). The authors thank David Razidlo and Bridget Stensgard for mouse colony maintenance, the Mayo Clinic Summer Undergraduate Research Fellowship program for funding, and the Mayo Clinic Biomaterials and Quantitative Histomorphometry Core Laboratory for assistance with histological specimen preparation.

Keywords

  • DNA damage
  • Histone deacetylase
  • Osteoblast
  • Osteocalcin-Cre
  • Osteocyte

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