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

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92 Scopus citations


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
Issue number31
Publication statusPublished - Aug 1 2003


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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