Cytokine-specific induction of the TGF-β inducible early gene (TIEG): Regulation by specific members of the TGF-β family

Theresa E. Hefferan, M. Subramaniam, Sundeep Khosla, B. Lawrence Riggs, Thomas C. Spelsberg

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Select members of the TGF-β family of cytokines play key regulatory roles in skeletal development, structure, and turnover. This laboratory has previously reported that TGF-β treatment of immortalized normal human fetal osteoblast (hFOB) cells results in the rapid induction of the mRNA levels of a TGF-β inducible early gene (TIEG) followed by changes in cell proliferation and bone matrix protein production. Previous studies have also shown that nonmembers of the TGF-β superfamily showed little or no induction of TIEG mRNA. This article further addresses the cytokine specificity of this TIEG induction by examining whether activin and select bone morphogenetic proteins, (BMP-2, BMP-4, and BMP-6), which are representative of different subfamilies of this superfamily, also induce the expression of TIEG in hFOB cells. However, TGF-β remained the most potent of these cytokines, inducing TIEG mRNA steady-state levels at 0.1 ng/ml, with a maximum induction of 24-fold at 2.0 ng/ml. The BMP-2 (16-fold), BMP-4 (4-fold), and activin (1-3-fold) also induced TIEG mRNA levels, but at reduced degrees compared to TGF-β (24-fold), and only at much higher cytokine concentrations, e.g., 50-100 ng/ml, compared to 2 ng/ml for TGF-β. BMP-6 showed no effect on TIEG mRNA levels. The TIEG protein levels generally correlated with the mRNA steady-state levels. As with TGF-β, BMP-2 treatment of hFOB cells was shown by confocal microscopy to induce a rapid translocation of the TIEG protein to the nucleus. In summary, the relative potencies of these TGF-β family members to induce TIEG expression generally follows the general osteoinductive capacity of these cytokines, with TGF-β >>> BMP-2 > BMP-4 > activin >> BMP-6. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)380-390
Number of pages11
JournalJournal of cellular biochemistry
Issue number3
StatePublished - 2000


  • BMPs
  • Early gene
  • Osteoblasts
  • TGF-β
  • TIEG
  • mRNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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