| Project/Area Number |
11671846
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional basic dentistry
|
|---|
| Research Institution | Saga Medical School |
|---|
Principal Investigator |
KUKITA Akiko Saga Medical School, Medicine, Associate Professor, 医学部, 助教授 (30153266)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUKITA Toshio Kyushu University, Dentistry, Associate Professor, 大学院・歯学研究院, 助教授 (70150464)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | osteoclast / differentiation / transcription factor |
|---|
| Research Abstract |
Osteoclasts and macrophage are closely related cells and are thought to be derived from common progenitor cells. A zinc finger transcription factor, Egr-1 was found to be a positive modulator of macrophage differentiation. We previously have shown that blocking Egr-1 expression by antisense oligonucleotides results in the stimulation of osteoclast differentiation in bone marrow culture. These data suggested that factor which inhibits Egr-1 function is involved in osteoclast differentiation. In this study, we show a BTB/POZ Zn finger gene, OCZF (osteoclast-derived zinc finger protein) isolated from osteoclast cDNA library efficiently suppresses Egr-1-dependent transcriptional activity. Analysis of the activity of deletion mutant OCZF proteins showed that the POZ and proline-rich domains contribute the activity of transcription repression. The trichostatin A (TSA), a specific inhibitor of histone deacetylases (HDAC) significantly reduced the repression effect of OCZF.Interestingly, the addition of TSA severely reduced osteoclast differentiation in bone marrow culture. TSA also strongly inhibited osteoclast differentiation from a macrophage cell line, RAW 264 which can differentiate into osteoclasts by the stimulation of RANKL.We also found that the expression of OCZF was increased along the osteoclast differentiation in this cell line, RAW 264. Ecotropic expression of OCZF in RAW 264 cells resulted in growth inhibition. These results suggest that OCZF is a unique transcriptional regulator which selectively represses the transcription of Egr-1-responsive gene and is induced by RANKL and participates in the regulation of cell growth in macrophage cell. In addition, we show that HDAC activity is required for osteoclast differentiation and OCZF may be contributed to the partial activity of HDAC necessary for osteoclast differentiation.
|
