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Nephroblastoma Overexpressed (Nov) Is a Novel Bone Morphogenetic Protein Antagonist
Author(s) -
CANALIS ERNESTO
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.055
Subject(s) - wnt signaling pathway , bone morphogenetic protein , microbiology and biotechnology , osteocalcin , bmpr2 , bone morphogenetic protein 7 , bone morphogenetic protein 2 , in vitro , bone morphogenetic protein 10 , bone morphogenetic protein 8a , chemistry , transcription factor , biology , endocrinology , medicine , signal transduction , gene , biochemistry , alkaline phosphatase , enzyme
: Nephroblastoma overexpressed (Nov), a member of the CCN family of proteins, is expressed by osteoblasts and its transcription is regulated by transforming growth factor (TGF)‐β and bone morphogenetic proteins (BMP). CCN proteins can interact with TGF‐β, BMPs, and Wnt. We explored the function of Nov in skeletal cells, in vitro and in vivo . Constitutive overexpression of Nov in cells of the osteoblastic lineage impaired osteoblastic differentiation, opposed the biological effects of BMP‐2 and Wnt 3 and impaired BMP‐2 and Wnt signaling, indicating that Nov has BMP‐2 antagonistic activity. Transgenic mice overexpressing Nov under the control of the osteocalcin promoter exhibited osteopenia secondary to decreased bone formation, confirming the effects in vitro . GST pulldown experiments demonstrated direct Nov–BMP interactions. In conclusion, Nov has BMP antagonistic properties and inhibits osteoblastogenesis and osteoblastic function.