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NF-κB Specifically Activates BMP-2 Gene Expression in Growth Plate Chondrocytes in Vivo and in a Chondrocyte Cell Line in Vitro.
- Source :
-
Journal of Biological Chemistry . 8/1/2003, Vol. 278 Issue 31, p29130. 6p. 13 Color Photographs, 1 Diagram, 1 Chart, 6 Graphs. - Publication Year :
- 2003
-
Abstract
- Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-κB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-κB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-κBα expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-κB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-κB subunits p50 and p65 bound to the NF-κB response elements of the BMP-2 gene. Thus, NF-κB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-κB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2′-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-κB, which may play an important role in chondrogenesis. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GENE expression
*GROWTH plate
*CARTILAGE cells
*CELL lines
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 278
- Issue :
- 31
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 10585735
- Full Text :
- https://doi.org/10.1074/jbc.M212296200