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Osteoblast Differentiation Stage-Specific Expression of the Pyrophosphate-Generating Enzyme PC-1
- Source :
- Cells Tissues Organs. 189:65-69
- Publication Year :
- 2008
- Publisher :
- S. Karger AG, 2008.
-
Abstract
- Fibroblast growth factor (FGF) signaling plays a critical role in skeletal development, yet the mechanism by which FGFs affect bone mineralization is not well understood. Review of the literature investigating effects of FGF signaling on bone mineralization indicates that FGFs may stimulate expression of factors that prevent mineralization in the short term and enhance mineralization in the long term. Pyrophosphate is an ideal example of a factor that, dependent upon environment, has the capacity to inhibit or enhance mineralization. PC-1 is the primary generator of pyrophosphate in osteoblastic cells; therefore, regulated expression of PC-1 by FGFs may be a principal mechanism by which FGF signaling affects bone mineralization. We previously showed that FGF2 induces PC-1 expression in preosteoblastic cells and that this induction is differentiation stage dependent. In order to more directly investigate the mechanism by which PC-1 expression is regulated, we have cloned a 2.8-kb region of the PC-1 gene promoter and constructed a PC-1 gene promoter/firefly luciferase reporter construct. Results indicate that this construct is specifically responsive to FGF2 or ascorbate (an inducer of osteoblast differentiation). Promoter responsiveness to FGF2 is significantly diminished upon osteoblast differentiation, and increases in promoter activity that occur with osteoblast differentiation are inhibited by FGF2 treatment. These results indicate that the mechanism of PC-1 induction by FGF2 in preosteoblastic cells is distinct from the mechanism of induction that occurs with osteoblast differentiation. These results also indicate that PC-1 may play multiple and distinct roles in the development of mineralized tissues.
- Subjects :
- Paper
Histology
Cellular differentiation
Biology
Fibroblast growth factor
Models, Biological
Mineralization (biology)
Cell Line
Mice
medicine
Animals
Humans
Luciferase
Inducer
Pyrophosphatases
Promoter Regions, Genetic
Osteoblasts
Phosphoric Diester Hydrolases
Cell Differentiation
Promoter
Osteoblast
Cell biology
Diphosphates
medicine.anatomical_structure
Biochemistry
Cell culture
Fibroblast Growth Factor 2
Anatomy
Subjects
Details
- ISSN :
- 14226421 and 14226405
- Volume :
- 189
- Database :
- OpenAIRE
- Journal :
- Cells Tissues Organs
- Accession number :
- edsair.doi.dedup.....0915c1fcf843cacf8e23cc4866b41b9d