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BMP‐2 induces the expression of activin βA and follistatin in vitro
Author(s) -
Kearns Ann E.,
Demay Marie B.
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/1097-4644(2000)79:1<80::aid-jcb80>3.0.co;2-k
Subject(s) - follistatin , in vitro , microbiology and biotechnology , chemistry , expression (computer science) , acvr2b , activin type 2 receptors , biology , tgf beta signaling pathway , transforming growth factor , computer science , biochemistry , programming language
Activins are members of the transforming growth factor β (TGF‐β) superfamily and have been shown to be multifunctional regulators of development and cell differentiation. Increasing evidence suggests activin βA is involved in skeletal development. Using differential display PCR we have identified activin βA as a gene associated with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) induced differentiation of a mouse limb bud cell line, MLB13MYC clone 17, from a prechondroblastic to an osteoblastic phenotype. The expression of activin βA peaks at 24 h of rhBMP‐2 treatment, before detection of osteocalcin mRNA expression. Cycloheximide treatment inhibits induction of activin βA, indicating a requirement for new protein synthesis. The induction of the mRNA encoding follistatin, an activin binding protein, was also examined. Follistatin mRNA increases within 18 h of rhBMP‐2 treatment, as activin βA mRNA increases but before it peaks. Treatment of MLB13MYC clone 17 cells with purified activin βA concomitant with rhBMP‐2 does not affect markers of chondrocyte or osteoblast differentiation, nor does treatment with purified activin βA alone. This suggests that activin βA exerts its effect via a paracrine mechanism. In situ hybridization analysis demonstrates that activin βA expression is localized to cells in the developing interphalangeal joints of embryonic mouse limbs. This is consistent with in vivo induction by BMP‐2 which is also expressed in the developing joints. Activin βA, therefore, is downstream from BMP‐2 in the cascade of events that result in skeletal development. J. Cell. Biochem. 79:80–88, 2000. © 2000 Wiley‐Liss, Inc.