Abstract
C-src is known to play an essential role in osteoclastogenesis. We studied the regulatory mechanism as well as the significance of c-src induction in RANKL-induced differentiation of mouse monocytic RAW264 cells to TRAP-positive-multinucleated cells. We determined the genomic organization of the 5'-terminal region of mouse c-src. Mutational and biochemical analyses in the region 0.9 kb upstream of the transcription start site revealed that c-Fos and JNK pathways, in addition to NF-kappaB, participate in c-src induction in response to RANKL. On the other hand, when the expression of c-src was suppressed by introducing antisense src, the number of multinucleated cells formed was significantly reduced. Together, these findings show that the expression of c-src is under the control of AP-1 and NF-kappaB in the differentiation of RAW264 cells and that c-src plays an essential role at the stage of progression to multinucleated cell formation.
| Original language | English |
|---|---|
| Pages (from-to) | 758-68 |
| Number of pages | 11 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 325 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Dec 17 2004 |
Keywords
- Animals
- Carrier Proteins
- Cell Differentiation
- Cell Proliferation
- Dose-Response Relationship, Drug
- Gene Expression Regulation
- Giant Cells
- Macrophages
- Membrane Glycoproteins
- Mice
- NF-kappa B
- Proto-Oncogene Proteins pp60(c-src)
- RANK Ligand
- Receptor Activator of Nuclear Factor-kappa B
- Transcription Factor AP-1
- Journal Article