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Follistatin Restricts Bone Morphogenetic Protein (BMP)‐2 Action on the Differentiation of Osteoblasts in Fetal Rat Mandibular Cells
Author(s) -
Abe Yukiko,
Abe Tatsuya,
Aida Yoshitomi,
Hara Yoshitaka,
Maeda Katsumasa
Publication year - 2004
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.040408
Subject(s) - follistatin , bone morphogenetic protein 2 , endocrinology , medicine , osteoblast , secretion , bone morphogenetic protein , chemistry , microbiology and biotechnology , biology , in vitro , biochemistry , gene
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.