Follistatin restricts bone morphogenetic protein (BMP)-2 action on the differentiation of osteoblasts in fetal rat mandibular cells

J Bone Miner Res. 2004 Aug;19(8):1302-7. doi: 10.1359/JBMR.040408. Epub 2004 May 3.


We tested whether FS secretion might modulate BMP-2 actions by measuring FS levels and counting bone numbers of rat mandibular cells. In the presence of Dex, BMP-2 stimulated FS secretion at the early phase and augmented bone nodule by neutralizing with FS antibody. We concluded that BMP-2 facilitates FS secretion, and the FS restricts BMP-2 action on osteoblastogenesis.

Introduction: Bone morphogenetic proteins (BMPs) promote the differentiation of osteoprogenitor cells into osteoblasts. Activin A is involved in the regulation of bone formation. Follistatin (FS) antagonizes the bioactivities of BMP and activin A extracellularly.

Materials and methods: In this study, we tested whether the induction of FS secretion might modulate the effects of BMP-2 on osteoblast development, using the bone nodule-forming cultures of fetal rat mandibular cells.

Results and conclusions: In the presence of dexamethasone (Dex), BMP-2 stimulated the secretion of FS at the early phase (days 3-9) of the culture. Dex alone had no effect, and BMP-2 alone was less effective than the combination of the two. BMP-4 and -6 had little effect on FS secretion. Activin A inhibited the early upregulation of FS secretion when added with BMP-2 and Dex. In the presence of Dex, BMP-2 increased bone nodule numbers when added to early cultures. The addition of anti-FS antibody to cultures with BMP-2 and Dex augmented bone nodule formation. These results show that BMP-2 facilitates the secretion of FS in the presence of Dex, and the increased FS secretion restricts the action of BMP-2 on osteoblast differentiation.

MeSH terms

  • Activins / pharmacology
  • Alkaline Phosphatase / metabolism
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Fetus
  • Follistatin / immunology
  • Follistatin / metabolism
  • Follistatin / pharmacology*
  • Humans
  • Inhibin-beta Subunits / pharmacology
  • Mandible
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects
  • Osteogenesis / physiology
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor beta / pharmacology*


  • Antibodies, Monoclonal
  • BMP2 protein, human
  • BMP4 protein, human
  • BMP6 protein, human
  • Bmp2 protein, rat
  • Bmp4 protein, rat
  • Bmp6 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins
  • Follistatin
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • activin A
  • recombinant human bone morphogenetic protein-2
  • Activins
  • Dexamethasone
  • Inhibin-beta Subunits
  • Alkaline Phosphatase