PMID- 12511413
OWN - NLM
STAT- MEDLINE
DCOM- 20030620
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 9
DP  - 2003 May 1
TI  - Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress 
      differentiation into osteoclasts but not into macrophages.
PG  - 3451-9
AB  - Histone deacetylase (HDAC) inhibitors are emerging as a new class of anticancer 
      therapeutic agents and have been demonstrated to induce differentiation in some 
      myeloid leukemia cell lines. In this study, we show that HDAC inhibitors have a 
      novel action on osteoclast differentiation. The effect of 2 HDAC inhibitors, 
      trichostatin A (TSA) and sodium butyrate (NaB), on osteoclastogenesis was 
      investigated using rat and mouse bone marrow cultures and a murine macrophage 
      cell line RAW264. Both TSA and NaB inhibited the formation of preosteoclast-like 
      cells (POCs) and multinucleated osteoclast-like cells (MNCs) in rat bone marrow 
      culture. By reverse transcription-polymerase chain reaction analysis, TSA reduced 
      osteoclast-specific mRNA expression of cathepsin K and calcitonin receptor (CTR). 
      In contrast, TSA and NaB did not affect the formation of bone marrow macrophages 
      (BMMs) induced by macrophage colony-stimulating factor as examined by nonspecific 
      esterase staining. Fluorescence-activated cell sorting analysis showed that TSA 
      did not affect the surface expression of macrophage markers for CD11b and F4/80 
      of BMMs. TSA and NaB also inhibited osteoclast formation and osteoclast-specific 
      mRNA expression in RAW264 cells stimulated with receptor activator of nuclear 
      factor-kappa B (NF-kappa B) ligand (RANKL). Transient transfection assay revealed 
      that TSA and NaB dose dependently reduced the sRANKL-stimulated or tumor necrosis 
      factor alpha (TNF-alpha)-stimulated transactivation of NF-kappa B-dependent 
      reporter genes. The treatment of RAW264 cells with TSA and NaB inhibited 
      TNF-alpha-induced nuclear translocation of NF-kappa B and sRANKL-induced 
      activation of p38 mitogen-activated protein kinase (MAPK) signals. These data 
      suggest that both TSA and NaB exert their inhibitory effects by modulating 
      osteoclast-specific signals and that HDAC activity regulates the process of 
      osteoclastogenesis.
FAU - Rahman, Md Mizanur
AU  - Rahman MM
AD  - Department of Microbiology, Saga Medical School, Nabeshima, Saga, Japan.
FAU - Kukita, Akiko
AU  - Kukita A
FAU - Kukita, Toshio
AU  - Kukita T
FAU - Shobuike, Takeo
AU  - Shobuike T
FAU - Nakamura, Takahiro
AU  - Nakamura T
FAU - Kohashi, Osamu
AU  - Kohashi O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030102
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Butyrates)
RN  - 0 (CD11b Antigen)
RN  - 0 (Carrier Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RANK Ligand)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Receptors, Calcitonin)
RN  - 0 (Tnfrsf11a protein, mouse)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (monocyte-macrophage differentiation antigen)
RN  - 3X2S926L3Z (trichostatin A)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.22.38 (Cathepsin K)
RN  - EC 3.4.22.38 (Ctsk protein, mouse)
RN  - EC 3.4.22.38 (Ctsk protein, rat)
SB  - IM
MH  - Animals
MH  - Antigens, Differentiation/analysis
MH  - Bone Marrow Cells/cytology/*drug effects
MH  - Butyrates/*pharmacology
MH  - CD11b Antigen/analysis
MH  - Carrier Proteins/pharmacology
MH  - Cathepsin K
MH  - Cathepsins/genetics
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured/cytology/drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - Flow Cytometry
MH  - *Histone Deacetylase Inhibitors
MH  - Hydroxamic Acids/*pharmacology
MH  - MAP Kinase Signaling System
MH  - Macrophage-1 Antigen/analysis
MH  - Macrophages/*chemistry/drug effects
MH  - Male
MH  - Membrane Glycoproteins/pharmacology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Osteoclasts/*cytology
MH  - RANK Ligand
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Receptors, Calcitonin/genetics
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/pharmacology
EDAT- 2003/01/04 04:00
MHDA- 2003/06/21 05:00
CRDT- 2003/01/04 04:00
PHST- 2003/01/04 04:00 [pubmed]
PHST- 2003/06/21 05:00 [medline]
PHST- 2003/01/04 04:00 [entrez]
AID - S0006-4971(20)50723-4 [pii]
AID - 10.1182/blood-2002-08-2622 [doi]
PST - ppublish
SO  - Blood. 2003 May 1;101(9):3451-9. doi: 10.1182/blood-2002-08-2622. Epub 2003 Jan 
      2.