title: Histone deacetylase 3 is required for maintenance of bone mass during aging.
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.
authors.affiliation: Department of Orthopedic Surgery/Orthopedic Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: McGee-Lawrence
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Bradley
authors.forename: Amel
authors.initials: A
authors.lastname: Dudakovic
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Carlson
authors.forename: Zachary C
authors.initials: ZC
authors.lastname: Ryan
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Mahrokh
authors.initials: M
authors.lastname: Dadsetan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Chen
authors.forename: Kai-Nan
authors.initials: KN
authors.lastname: An
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
mesh_terms: D015502:Absorptiometry, Photon; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015519:Bone Density; D004249:DNA Damage; D017931:DNA Primers; D006655:Histone Deacetylases / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D015675:Osteocalcin / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D000099186:Histone Deacetylase 3
chemical_list: D017931:DNA Primers; D006655:Histone Deacetylases; D015675:Osteocalcin; D000099186:Histone Deacetylase 3