NF-κB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro

Jian Q. Feng, Lianping Xing, Jiang Hong Zhang, Ming Zhao, Diane Horn, Jeannie Chan, Brendan F. Boyce, Stephen E. Harris, Gregory R. Mundy, Di Chen

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

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. Co-transfection 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.

Original languageEnglish (US)
Pages (from-to)29130-29135
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number31
DOIs
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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