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J Bone Joint Surg Am. 2001;83-A Suppl 1(Pt 1):S48-55.

Intimate relationship between TGF-beta/BMP signaling and runt domain transcription factor, PEBP2/CBF.

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1
Department of Biochemistry, School of Medicine, and Medical Research Institute, Chungbuk National University, Cheongju, Korea.

Abstract

BACKGROUND:

When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factor-beta1 (TGF-beta1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein-2 (BMP-2) not only blocks myogenic differentiation but also induces osteoblastic differentiation. However, the molecular mechanisms governing the ability of TGF-beta and BMP to induce ligand-specific responses and inhibit myogenic differentiation are not known. The objective of our studies was to elucidate the molecular mechanisms that block myoblastic differentiation and induce osteoblastic differentiation in C2C12 cells.

METHODS:

Induction of RUNX2/PEBP2alphaA/Cbfa1 by TGF-beta and BMP was examined by electrophoretic mobility shift assay (EMSA) and Northern blot analysis. C2C12 cells stably expressing RUNX2 or Smad, or both, were established, and the role of these genes in the process of osteoblastic differentiation was analyzed by examining the expression of osteoblast-specific markers.

RESULTS:

Treatment of C2C12 with TGF-beta and BMP-induced RUNX2/PEBP2alphaA/Cbfa1, a global regulator of osteogenesis. Cooperation between RUNX2 and BMP-activated Smad induced osteoblastic differentiation.

CONCLUSIONS:

Both TGF-beta and BMP activate transcription of RUNX2, which is sufficient to inhibit myogenesis. To induce osteogenesis, BMP-induced RUNX2 must cooperate with BMP-activated Smads.

PMID:
11263665
[Indexed for MEDLINE]
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