Abstract
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-κB (NF-κB) ligand (RANKL). Transient transfection assay revealed that TSA and NaB dose dependently reduced the sRANKL-stimulated or tumor necrosis factor α (TNF-α)-stimulated transactivation of NF-κB-dependent reporter genes. The treatment of RAW264 cells with TSA and NaB inhibited TNF-α-induced nuclear translocation of NF-κB 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.
| Original language | English |
|---|---|
| Pages (from-to) | 3451-3459 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 101 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - May 1 2003 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Immunology
- Hematology
- Cell Biology
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Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages. / Rahman, Mizanur; Kukita, Akiko; Kukita, Toshio; Shobuike, Takeo; Nakamura, Takahiro; Kohashi, Osamu.
In: Blood, Vol. 101, No. 9, 01.05.2003, p. 3451-3459.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages
AU - Rahman, Mizanur
AU - Kukita, Akiko
AU - Kukita, Toshio
AU - Shobuike, Takeo
AU - Nakamura, Takahiro
AU - Kohashi, Osamu
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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-κB (NF-κB) ligand (RANKL). Transient transfection assay revealed that TSA and NaB dose dependently reduced the sRANKL-stimulated or tumor necrosis factor α (TNF-α)-stimulated transactivation of NF-κB-dependent reporter genes. The treatment of RAW264 cells with TSA and NaB inhibited TNF-α-induced nuclear translocation of NF-κB 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.
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-κB (NF-κB) ligand (RANKL). Transient transfection assay revealed that TSA and NaB dose dependently reduced the sRANKL-stimulated or tumor necrosis factor α (TNF-α)-stimulated transactivation of NF-κB-dependent reporter genes. The treatment of RAW264 cells with TSA and NaB inhibited TNF-α-induced nuclear translocation of NF-κB 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.
UR - http://www.scopus.com/inward/record.url?scp=0038542837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038542837&partnerID=8YFLogxK
U2 - 10.1182/blood-2002-08-2622
DO - 10.1182/blood-2002-08-2622
M3 - Article
C2 - 12511413
AN - SCOPUS:0038542837
VL - 101
SP - 3451
EP - 3459
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -