Nephroblastoma overexpressed (Nov) is a novel bone morphogenetic protein antagonist

被引：17

作者：

Canalis, Ernesto ^{[1
,2
]}

机构：

[1] St Francis Hosp & Med Ctr, Dept Res, Hartford, CT 06105 USA

[2] Univ Connecticut, Sch Med, Farmington, CT USA

来源：

SKELETAL BIOLOGY AND MEDICINE, PT A: ASPECTS OF BONE MORPHOGENESIS AND REMODELING | 2007年 / 1116卷

关键词：

bone morphogenetic proteins (BMP); BMP antagonists; CCN proteins; nephroblastoma overexpressed; notch; osteoblastogenesis; Wnt; VAN-BUCHEM-DISEASE; TGF-BETA; OSTEOBLASTIC DIFFERENTIATION; INHIBITS OSTEOBLASTOGENESIS; CHONDROCYTE MATURATION; SKELETAL DEVELOPMENT; SIGNALING PATHWAYS; POSSIBLE MECHANISM; CAUSES OSTEOPENIA; CCN3; NOV;

D O I：

10.1196/annals.1402.055

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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)-beta and bone morphogenetic proteins (BMP). CCN proteins can interact with TGF-beta, 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.

引用

页码：50 / 58

页数：9

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