Histone deacetylases (HDAC) in physiological and pathological bone remodelling

Histone deacetylases (HDACs)22Histone deacetylases (HDACs). play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi)33HDAC inhibitors (HDACi). that act on multiple HDAC enzymes ha...

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Published in:Bone (New York, N.Y.) Vol. 95; pp. 162 - 174
Main Authors: Cantley, M.D., Zannettino, A.C.W., Bartold, P.M., Fairlie, D.P., Haynes, D.R.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.02.2017
Subjects:
Animals
Bone Remodeling - physiology
Cell Differentiation - drug effects
Histone Deacetylase Inhibitors - pharmacology
Histone deacetylases (HDAC)
Histone Deacetylases - metabolism
Humans
Myeloma bone disease
Orthopedics
Osteoblasts
Osteoblasts - drug effects
Osteoblasts - metabolism
Osteoclasts
Osteoclasts - drug effects
Osteoclasts - metabolism
Periodontitis
Rheumatoid arthritis
RANKL
Histone deacetylases (HDAC)
CTCL
PTH
ALP
NFATc1
TRAP
Osteoblasts
Myeloma bone disease
RASFs
shRNA
SOST
HDACi
MM
SAHA
TSA
BMM
siRNA
RA
BMPs
Periodontitis
TNF-α
TRAF-6
Rheumatoid arthritis
Osteoclasts
HDAC
trichostatin A
cutaneous T-cell lymphoma
small interfering RNA
tumour necrosis factor (TNF) receptor associated factor-6
short hairpin RNA
alkaline phosphatase
tumour necrosis factor alpha
bone marrow macrophages
histone deacetylase inhibitors
bone morphogenetic proteins
parathyroid hormone
multiple myeloma
receptor activator of nuclear factor kappa B ligand
histone deacetylase
rheumatoid arthritis synovial fibroblasts
nuclear factor of activated T cells
sclerostin
tartrate resistant acid phosphatase
suberanilohydroxamic acid
ISSN:8756-3282, 1873-2763, 1873-2763
Online Access:Get full text
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Summary:Histone deacetylases (HDACs)22Histone deacetylases (HDACs). play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi)33HDAC inhibitors (HDACi). that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are also currently being studied for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes. Selective isozyme-specific inhibitors currently being developed against class I HDACs (1, 2, 3 and 8) and class II HDACs (4, 5, 6, 7, 9 and 10) will be valuable tools for elucidating the roles played by individual HDACs in different physiological and pathological settings. Isozyme-specific HDACi promise to have greater efficacy and reduced side effects, as required for treating chronic disease over extended periods of time. This article reviews the current understanding of roles for individual HDAC isozymes and effects of HDACi on bone cells, (osteoblasts, osteoclasts and osteocytes), in relation to bone remodelling in conditions characterised by pathological bone loss, including periodontitis, rheumatoid arthritis and myeloma bone disease. •HDACi can regulate bone remodelling by suppressing osteoclasts and promoting osteoblasts•HDAC isozymes have differing roles in differentiation and function of bone cells, osteoclasts, osteoblasts and osteocytes.•Novel isozyme-specific HDACi are critical to elucidate HDAC roles in bone remodelling and communication between bone cells.•For non-malignancies, such inflammatory arthritis, HDACi can be more beneficial in vivo at much lower doses.
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ISSN:8756-3282
1873-2763
1873-2763
DOI:10.1016/j.bone.2016.11.028