Bone morphogenetic proteins induce the expression of noggin, which limits their activity in cultured rat osteoblasts

Elisabetta Gazzerro, Valerie Gangji, Ernesto Canalis

Research output: Contribution to journalArticlepeer-review

Abstract

bone morphogenetic proteins (BMPs) induce the differentiation of cells of the osteoblastic lineage and enhance the function of the osteoblast. Growth factors are regulated by binding proteins, but there is no information about binding proteins for BMPs in skeletal cells. Noggin specifically binds BMPs, but its expression by cells of the osteoblastic lineage has not been reported. We tested for the expression of noggin and its induction by BMP-2 in cultures of osteoblast-enriched cells from 22-d-old fetal rat calvariae (Ob cells). BMP-2 caused a time- and dose-dependent increase in noggin mrna and polypeptide levels, as determined by Northern and Western blot analyses. The effects of BMP-2 on noggin transcripts were dependent on protein, but independent of Dna synthesis. BMP-2 increased the rates of noggin transcription as determined by nuclear run-on assays. BMP-4, BMP-6, and TGF- β1 increased noggin mrna in Ob cells, but basic fibroblast growth factor, platelet-derived growth factor BB, and IGF-I did not. Noggin decreased the stimulatory effects of BMPs on Dna and collagen synthesis and alkaline phosphatase activity in Ob cells. In conclusion, BMPs induce noggin transcription in Ob cells, a probable mechanism to limit BMP action in osteoblasts.

Original languageEnglish
Pages (from-to)2106-2114
Number of pages9
JournalJournal of Clinical Investigation
Volume102
Issue number12
Publication statusPublished - Dec 15 1998

Keywords

  • Binding proteins
  • Bone formation
  • Chordin
  • Osteogenic proteins
  • Transcription

ASJC Scopus subject areas

  • Medicine(all)

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