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


BACKGROUND
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.


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.


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.
Abe
Yukiko
Y
Division of Periodontology, Department of Developmental and Reconstructive Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School, Nagasaki, Japan. d900175h@stcc.nagasaki-u.ac.jp
Abe
Tatsuya
T
Aida
Yoshitomi
Y
Hara
Yoshitaka
Y
Maeda
Katsumasa
K
D028341:Activins / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D038681:Follistatin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000494:pharmacology; D008334:Mandible; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525816:BMP6 protein, human; C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; C525818:Bmp6 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C422405:activin A; C499469:recombinant human bone morphogenetic protein-2; D028341:Activins; D003907:Dexamethasone; D028322:Inhibin-beta Subunits; D000469:Alkaline Phosphatase